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82-682: The Fred Hutchinson Cancer Center , formerly known as the Fred Hutchinson Cancer Research Center and also known as Fred Hutch or The Hutch , is a cancer research institute established in 1975 in Seattle , Washington . The center grew out of the Pacific Northwest Research Foundation , founded in 1956 by William B. Hutchinson (1909–1997). The Foundation was dedicated to the study of heart surgery , cancer, and diseases of

164-665: A time capsule set to open in 2093. The campus is accessible via the Mercer Street exit of Interstate 5 as well as several public transportation routes, including the South Lake Union Streetcar . Seattle Seattle ( / s i ˈ æ t əl / see- AT -əl ) is a city on the West Coast of the United States . It is the seat of King County , Washington . With

246-549: A $ 265 million initial public offering in 2014, was started based on inventions made at the center. As of 2015, about twenty companies had been started based on center inventions since 1975, including Immunex and Icos . The institute's main campus consists of 13 buildings that are on fifteen acres (6.1 ha) in the South Lake Union neighborhood of Seattle. In 1987, the center began exploring possible new homes to replace its 9-building campus on First Hill that it

328-708: A 1-to-1 ratio of the cell types apparently provide synergistic antitumor effects. The first chimeric receptors containing portions of an antibody and the T cell receptor was described in 1987 by Yoshihisa Kuwana et al. at Fujita Health University and Kyowa Hakko Kogyo, Co. Ltd. in Japan, and independently in 1989 by Gideon Gross and Zelig Eshhar at the Weizmann Institute in Israel. Originally termed "T-bodies", these early approaches combined an antibody's ability to specifically bind to diverse targets with

410-503: A 2023 population of 755,078 it is the most populous city in both the state of Washington and the Pacific Northwest region of North America , and the 18th-most populous city in the United States. The Seattle metropolitan area 's population is 4.02 million, making it the 15th-largest in the United States. Its growth rate of 21.1% between 2010 and 2020 made it one of the country's fastest-growing large cities. Seattle

492-1192: A CAR T cell that can eradicate a certain cell population (for instance, CAR T cells that target lymphoma cells), there are other potential uses for this technology. T cells can also mediate tolerance to antigens. A regulatory T cell outfitted with a CAR could have the potential to confer tolerance to a specific antigen, something that could be utilized in organ transplantation or rheumatologic diseases like lupus . (Kymriah) EMA : 08/22/2018 MHLW : 05/15/2019 Diffuse large B-cell lymphoma (Third Line) Follicular lymphoma (Third Line) EMA :004090, Label (Yescarta) EMA : 08/27/2018 NMPA : 06/23/2021 MHLW : 12/22/2022 Follicular lymphoma (Third Line) Primary mediastinal large B-cell lymphoma (Third Line) EMA :004480, Label (Tecartus) EMA : 12/14/2020 B-cell precursor ALL (Third Line) EMA :005102, Label (Breyanzi) EMA : 04/04/2022 MHLW : 12/20/2022 EMA :004731, Label (Abecma) EMA : 08/18/2021 EMA :004662, Label (Carvykti) EMA : 05/25/2022 EMA :005095, Label (Aucatzyl) There are serious side effects that result from CAR T-cells being introduced into

574-432: A CD4 extracellular domain and a CD3ζ intracellular domain was used in the first clinical trial of chimeric antigen receptor T cells by the biotechnology company Cell Genesys in the mid 1990s, allowing adoptively transferred T cells to target HIV infected cells, although it failed to show any clinical improvement. Similar early clinical trials of CAR T cells in solid tumors in the 1990s using first generation CARs targeting

656-405: A cell-processing center. In the cell processing center, specific T cells are stimulated so that they will actively proliferate and expand to large numbers. To drive their expansion, T cells are typically treated with the cytokine interleukin 2 (IL-2) and anti- CD3 antibodies. Anti-CD3/CD28 antibodies are also used in some protocols. The expanded T cells are purified and then transduced with

738-546: A gateway to Alaska during the Klondike Gold Rush . The city grew after World War II , partly due to the local company Boeing , which established Seattle as a center for its manufacturing of aircraft. Beginning in the 1980s, the Seattle area developed into a technology center ; Microsoft established its headquarters in the region. In 1994, Internet retailer Amazon was founded in Seattle, and Alaska Airlines

820-553: A gene encoding the engineered CAR via a retroviral vector , typically either an integrating gammaretrovirus (RV) or a lentiviral (LV) vector. These vectors are very safe in modern times due to a partial deletion of the U3 region. The new gene editing tool CRISPR/Cas9 has recently been used instead of retroviral vectors to integrate the CAR gene into specific sites in the genome. The patient undergoes lymphodepletion chemotherapy prior to

902-634: A great frenzy among the technology companies in Seattle but the bubble ended in early 2001. In 1999, the World Trade Organization held its conference in Seattle, which was met with protest activity . The protests and police reactions to them largely overshadowed the conference itself. In 2001, the city was impacted by the Mardi Gras Riots and then by the Nisqually earthquake the following day. Another boom began as

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984-441: A number of technology companies, including Amazon , F5 Networks , RealNetworks , Nintendo of America , and T-Mobile . This success brought an influx of new residents with a population increase within city limits of almost 50,000 between 1990 and 2000, and saw Seattle's real estate become some of the most expensive in the country. Seattle in this period attracted attention as home to the companies opened operations in or around

1066-478: A number of theaters in the city exhibiting vaudeville acts and silent movies. He went on to become one of America's greatest theater and movie tycoons. Scottish-born architect B. Marcus Priteca designed several theaters for Pantages in Seattle, which were later demolished or converted to other uses. Seattle's surviving Paramount Theatre , on which he collaborated, was not a Pantages theater. War work again brought local prosperity during World War II , centered on

1148-401: A patient's tumor cells, then infused into the patient where they attack and kill the cancer cells. Adoptive transfer of T cells expressing CARs is a promising anti-cancer therapeutic, because CAR-modified T cells can be engineered to target potentially any tumor associated antigen . Early CAR T cell research has focused on blood cancers . The first approved treatments use CARs that target

1230-431: A prominent 19th-century leader of the local Duwamish and Suquamish tribes. Seattle currently has high populations of Native Americans alongside Americans with strong Asian, African, European, and Scandinavian ancestry, and, as of 2015, hosts the fifth-largest LGBT community in the U.S. Logging was Seattle's first major industry, but by the late 19th century the city had become a commercial and shipbuilding center as

1312-709: A result provokes an immune response. On-target/off-tumor recognition occurs when the CAR T-cell recognizes the correct antigen, but the antigen is expressed on healthy, non-pathogenic tissue. This results in the CAR T-cells attacking non-tumor tissue, such as healthy B cells that express CD19 causing B-cell aplasia . The severity of this adverse effect can vary but the combination of prior immunosuppression, lymphodepleting chemotherapy and on-target effects causing hypogammaglobulinaemia and prolonged cytopenias places patients at increased risk of serious infections. There

1394-485: A second time at the site of present-day Pioneer Square , naming this new settlement Duwamps . Charles Terry and John Low remained at the original landing location, reestablished their old land claim and called it "New York", but renamed "New York Alki" in April 1853, from a Chinook word meaning, roughly, "by and by" or "someday". For the next few years, New York Alki and Duwamps competed for dominance, but in time Alki

1476-420: A solid tumor antigens such as MUC1 did not show long-term persistence of the transferred T cells or result in significant remissions. In the early 2000s, co-stimulatory domains such as CD28 or 4-1BB were added to first generation CAR's CD3ζ intracellular domain. Termed second generation CARs, these constructs showed greater persistence and improved tumor clearance in pre-clinical models. Clinical trials in

1558-604: A total area of 142.5 square miles (369 km ), 84 square miles (220 km ) of which is land and 58.1 square miles (150 km ) is water (41% of the total area). According to the Köppen climate classification system, Seattle has a warm-summer Mediterranean climate ( Csb ), while under the Trewartha system, it is labeled an oceanic climate ( Dobk ). It has cool, wet winters and mild, relatively dry summers, covering characteristics of both climate types. The climate

1640-522: Is based in SeaTac, Washington , serving Seattle–Tacoma International Airport , Seattle's international airport. The stream of new software, biotechnology , and Internet companies led to an economic revival, which increased the city's population by almost 50,000 in the decade between 1990 and 2000. The culture of Seattle is heavily defined by its significant musical history . Between 1918 and 1951, nearly 24 jazz nightclubs existed along Jackson Street, from

1722-494: Is enough to show rapid tumor regression in a matter of days. Solid tumors have presented a more difficult target. Identification of good antigens has been challenging: such antigens must be highly expressed on the majority of cancer cells, but largely absent on normal tissues. CAR T cells are also not trafficked efficiently into the center of solid tumor masses, and the hostile tumor microenvironment suppresses T cell activity. While most CAR T cell studies focus on creating

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1804-506: Is hilly in some places. Like Rome, the city is said to lie on seven hills ; the lists vary but typically include Capitol Hill , First Hill , West Seattle , Beacon Hill , Queen Anne , Magnolia, and the former Denny Hill . The Wallingford , Delridge , Mount Baker , Seward Park , Washington Park , Broadmoor , Madrona , Phinney Ridge , Sunset Hill , Blue Ridge , Broadview , Laurelhurst , Hawthorne Hills , Maple Leaf , and Crown Hill neighborhoods are all located on hills. Many of

1886-680: Is situated on an isthmus between Puget Sound , an inlet of the Pacific Ocean , and Lake Washington . It is the northernmost major city in the United States, located about 100 miles (160 km) south of the Canadian border . A gateway for trade with East Asia , the Port of Seattle is the fourth-largest port in North America in terms of container handling as of 2021 . The Seattle area has been inhabited by Native Americans (such as

1968-491: Is sometimes characterized as a "modified Mediterranean" climate because it is cooler and wetter than a "true" Mediterranean climate, but shares the characteristic dry summer (which has a strong influence on the region's vegetation). Temperature extremes are moderated by the adjacent Puget Sound , greater Pacific Ocean , and Lake Washington . Thus extreme heat waves are rare in the Seattle area, as are very cold temperatures (below about 15 °F; −9 °C). The Seattle area

2050-568: Is the cloudiest region of the Continental United States , due in part to frequent storms and lows moving in from the adjacent Pacific Ocean. Seattle is cloudy 201 days out of the year and partly cloudy 93 days. With many more "rain days" than other major American cities, Seattle has a well-earned reputation for frequent rain: In an average year, there are 150 days in which at least 0.01 inches (0.25 mm) of precipitation falls, more days than in nearly all U.S. cities east of

2132-581: Is the isolation of T cells from human blood. CAR T-cells may be manufactured either from the patient's own blood, known as an autologous treatment, or from the blood of a healthy donor, known as an allogeneic treatment. The manufacturing process is the same in both cases; only the choice of initial blood donor is different. First, leukocytes are isolated using a blood cell separator in a process known as leukocyte apheresis . Peripheral blood mononuclear cells (PBMCs) are then separated and collected. The products of leukocyte apheresis are then transferred to

2214-477: Is to harvest T cells from patients, genetically alter them, then infuse the resulting CAR T cells into patients to attack their tumors. CAR T cells can be derived either autologously from T cells in a patient's own blood or allogeneically from those of a donor. Once isolated, these T cells are genetically engineered to express a specific CAR, using a vector derived from an engineered lentivirus such as HIV (see Lentiviral vector in gene therapy ). The CAR programs

2296-525: The 1962 World's Fair , for which the Space Needle was built. Another major local economic downturn was in the late 1960s and early 1970s, at a time when Boeing was heavily affected by the oil crises , loss of government contracts, and costs and delays associated with the Boeing 747 . Many people left the area to look for work elsewhere, and two local real estate agents put up a billboard reading "Will

2378-618: The Alaska–Yukon–Pacific Exposition of 1909, which is largely responsible for the layout of today's University of Washington campus. A shipbuilding boom in the early part of the 20th century became massive during World War I , making Seattle somewhat of a company town. The subsequent retrenchment led to the Seattle General Strike of 1919 , an early general strike in the country. A 1912 city development plan by Virgil Bogue went largely unused. Seattle

2460-569: The Duwamish , who had at least 17 villages around Elliot Bay) for at least 4,000 years before the first permanent European settlers. Arthur A. Denny and his group of travelers, subsequently known as the Denny Party , arrived from Illinois via Portland, Oregon , on the schooner Exact at Alki Point on November 13, 1851. The settlement was moved to the eastern shore of Elliott Bay in 1852 and named "Seattle" in honor of Chief Seattle ,

2542-663: The Lake Washington Ship Canal (consisting of two man-made canals, Lake Union , and the Hiram M. Chittenden Locks at Salmon Bay , ending in Shilshole Bay on Puget Sound). The sea, rivers, forests, lakes, and fields surrounding Seattle were once rich enough to support one of the world's few sedentary hunter-gatherer societies. In modern times the surrounding area lends itself well to sailing, skiing, bicycling, camping, and hiking year-round. The city

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2624-620: The Nobel Prize in Physiology or Medicine : The center is active in technology transfer . In 2013, it was one of the top ten biomedical research institutions in the field (excluding universities); it made 18 new deals with companies to develop inventions made at the center, and earned $ 10,684,882 in income from past deals it had signed. Most notably, Juno Therapeutics , a company developing CAR-T immunotherapy for cancer and that raised $ 314 million in venture capital investments and had

2706-790: The Pacific Ring of Fire , Seattle is in a major earthquake zone . On February 28, 2001, the magnitude 6.8 Nisqually earthquake did significant architectural damage, especially in the Pioneer Square area (built on reclaimed land , as are the Industrial District and part of the city center), and caused one fatality. Other strong earthquakes occurred on January 26, 1700 (estimated at 9 magnitude), December 14, 1872 (7.3 or 7.4), April 13, 1949 (7.1), and April 29, 1965 (6.5). The 1965 quake caused three deaths in Seattle directly and one more by heart failure. Although

2788-759: The Rocky Mountains . However, because it often has merely a light drizzle falling from the sky for many days, Seattle actually receives significantly less rainfall (or other precipitation) overall than many other major U.S. cities like New York City , Miami , or Houston . According to the 2012–2016 American Community Survey (ACS), the racial makeup of the city was 65.7% White Non-Hispanic , 16.9% Asian , 6.8% Black or African American , 6.6% Hispanic or Latino of any race, 0.4% Native American , 0.9% Pacific Islander , 0.2% other races, and 5.6% two or more races . Seattle's population historically has been predominantly white. The 2010 census showed that Seattle

2870-525: The Seattle Fault passes just south of the city center, neither it nor the Cascadia subduction zone has caused an earthquake since the city's founding. The Cascadia subduction zone poses the threat of an earthquake of magnitude 9.0 or greater, capable of seriously damaging the city and collapsing many buildings, especially in zones built on fill. According to the U.S. Census Bureau , the city has

2952-521: The US to the FDA 's first two approvals of CAR T cells in 2017, those for tisagenlecleucel (Kymriah), marketed by Novartis originally for B-cell precursor acute lymphoblastic leukemia (B-ALL), and axicabtagene ciloleucel (Yescarta), marketed by Kite Pharma originally for diffuse large B-cell lymphoma (DLBCL). There are now six FDA-approved CAR T therapies. The first step in the production of CAR T-cells

3034-518: The University of Washington negatively. As schools across Washington lost funding and attendance, the university actually prospered during the time period as they focused on growing their student enrollment. While Seattle public schools were influenced by Washington's superintendent Worth McClure, they still struggled to pay teachers and maintain attendance. Seattle was the home base of impresario Alexander Pantages who, starting in 1902, opened

3116-609: The anti-Chinese riots of 1885–1886 . This violence originated with unemployed whites who were determined to drive the Chinese from Seattle; anti-Chinese riots also occurred in Tacoma . Seattle had achieved sufficient economic success when the Great Seattle Fire of 1889 destroyed the central business district. However, a far grander city center rapidly emerged in its place. Finance company Washington Mutual , for example,

3198-719: The endocrine system . Hutchinson's younger brother Fred (1919–1964) was a major league pitcher and manager who died of lung cancer at age 45. The next year, William Hutchinson established the Fred Hutchinson Cancer Research Center as a division of the Pacific Northwest Research Foundation. In 1972, with the help of Senator Warren G. Magnuson , PNRF received federal funding under the National Cancer Act of 1971 to create in Seattle one of

3280-599: The 15 new NCI-designated Cancer Centers aimed at conducting basic research called for under 1971 Act; the Fred Hutchinson Cancer Research Center became independent 1972 and its building opened three years later in 1975. The center was named an NCI-designated Comprehensive Cancer Center in 1976. In 1998, the center formed the Seattle Cancer Care Alliance (SCCA), a separate nonprofit corporation, with University of Washington School of Medicine (UW Medicine), and Seattle Children's . This solidified

3362-542: The 1980s and early 1990s, patients were not informed about all the risks of the study, nor about the study doctors' financial interest in study outcome. The paper also alleged that this financial interest may have contributed to the doctors' failure to halt the studies despite evidence that patients were dying sooner and more frequently than expected. In response, the center formed a panel of independent experts to review its existing research practices, leading to adoption of new conflict-of-interest rules. In 2010 Lawrence Corey

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3444-750: The Pacific Ocean) to the west and Lake Washington to the east. The city's chief harbor, Elliott Bay , is part of Puget Sound, making the city an oceanic port. To the west, beyond Puget Sound, are the Kitsap Peninsula and Olympic Mountains on the Olympic Peninsula ; to the east, beyond Lake Washington and the Eastside suburbs, are Lake Sammamish and the Cascade Range . Lake Washington's waters flow to Puget Sound through

3526-683: The Seattle area and has been open to all residents of Washington since 2002. On March 20, 1970, twenty-eight people were killed when the Ozark Hotel was burned by an unknown arsonist. The Wah Mee massacre in 1983 resulted in the killing of 13 people in an illegal gambling club in the Seattle Chinatown-International District . Prosperity began to return in the 1980s beginning with Microsoft 's 1979 move from Albuquerque, New Mexico , to nearby Bellevue, Washington . Seattle and its suburbs became home to

3608-485: The Seattle area for at least 4,000 years. By the time the first European settlers arrived, the Duwamish people occupied at least 17 villages in the areas around Elliott Bay . The name for the modern city of Seattle in Lushootseed , dᶻidᶻəlal̓ič , meaning "little crossing-over place", comes from one of these villages, which was located at the present-day King Street Station . In May 1792, George Vancouver

3690-589: The T cells to target an antigen present on the tumor cell surface. For safety, CAR T cells are engineered to be specific to an antigen that is expressed on a tumor cell but not on healthy cells. After the modified T cells are infused into a patient, they act as a "living drug" against cancer cells. When they come in contact with their targeted antigen on a cell's surface, T cells bind to it and become activated, then proceed to proliferate and become cytotoxic . CAR T cells destroy cells through several mechanisms, including extensive stimulated cell proliferation, increasing

3772-691: The United States. According to the ACS 1-year estimates, in 2018, the median income of a city household was $ 93,481, and the median income for a family was $ 130,656. 11.0% of the population and 6.6% of families were below the poverty line. Of people living in poverty, 11.4% were under the age of 18 and 10.9% were 65 or older. According to a 2024 study by Henley & Partners , the city of Seattle has an estimated 54,200 millionaires and 11 billionaires. CAR-T CAR T cell therapy uses T cells engineered with CARs to treat cancer. T cells are modified to recognize cancer cells and destroy them. The standard approach

3854-548: The antigen CD19 , present in B-cell-derived cancers such as acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). There are also efforts underway to engineer CARs targeting many other blood cancer antigens, including CD30 in refractory Hodgkin's lymphoma ; CD33 , CD123 , and FLT3 in acute myeloid leukemia (AML); and BCMA in multiple myeloma . CAR T cells have also been found to be effective in treating glioblastoma.  A single infusion

3936-634: The bigger West Coast city. Seattle had building contracts that rivaled New York City and Chicago , but also lost to Los Angeles. Seattle's eastern farm land faded due to Oregon 's and the Midwest 's, forcing people into town. Hooverville arose during the Depression, leading to Seattle's growing homeless population. Stationed outside Seattle, the Hooverville housed thousands of men but very few children and no women. With work projects close to

4018-427: The body, including cytokine release syndrome and neurological toxicity. Because it is a relatively new treatment, there are few data about the long-term effects of CAR T-cell therapy. There are still concerns about long-term patient survival, as well as pregnancy complications in female patients treated with CAR T-cells. Anaphylaxis may be a side effect, as the CAR is made with a foreign monoclonal antibody , and as

4100-643: The center's reach into clinical care and was essential for it retaining its NCI comprehensive center designation; the designation was extended to the center's consortium including the SCCA in 2003. SCCA's outpatient clinic first opened in January 2001. In 2001, The Seattle Times published a series of articles alleging that investigators at the center (including the center's co-founder E. Donnall Thomas ) were conducting unethical clinical studies on cancer patients. The paper alleged that in two cancer studies conducted in

4182-493: The city emerged from the Great Recession , commencing when Amazon moved its headquarters from North Beacon Hill to South Lake Union . The move initiated a historic construction boom which resulted in the completion of almost 10,000 apartments in Seattle in 2017, more than any previous year and nearly twice as many as were built in 2016. From 2010 to 2015, Seattle gained an average of 14,511 residents per year, with

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4264-631: The city, Hooverville grew and the WPA settled into the city. A movement of women arose from Seattle during the Great Depression , fueled in part by Eleanor Roosevelt 's 1933 book It's Up to the Women ; women pushed for recognition, not just as housewives, but as the backbone to family. Using newspapers and journals Working Woman and The Woman Today , women pushed to be seen as equal and receive some recognition. The Great Depression did not impact

4346-546: The city. In 1990, the Goodwill Games were held in the city. Three years later, in 1993, the APEC leaders was hosted in Seattle. The 1990s also witnessed a growing popularity in grunge music, a sound that was largely developed in Seattle's independent music scene. In 1993, the movie Sleepless in Seattle brought the city further national attention, as did the television sitcom Frasier . The dot-com boom caused

4428-598: The constant domains of the TCR-α or TCR-β proteins. In 1991, chimeric receptors containing the intracellular signaling domain of CD3ζ were shown to activate T cell signaling by Arthur Weiss at the University of California, San Francisco . This work prompted CD3ζ intracellular domains to be added to chimeric receptors with antibody-like extracellular domains, commonly single-chain fraction variable (scFv) domains, as well as proteins such as CD4 , subsequently termed first generation CARs. A first generation CAR containing

4510-666: The current Chinatown/International District to the Central District . The jazz scene nurtured the early careers of Ernestine Anderson , Ray Charles , Quincy Jones , and others. In the late 20th and early 21st century, the city also was the origin of several rock bands, including Foo Fighters , Heart , and Jimi Hendrix , and the subgenre of grunge and its pioneering bands, including Alice in Chains , Nirvana , Pearl Jam , Soundgarden , and others. Archaeological excavations suggest that Native Americans have inhabited

4592-429: The degree to which they are toxic to other living cells (cytotoxicity), and by causing the increased secretion of factors that can affect other cells such as cytokines , interleukins and growth factors. The surface of CAR T cells can bear either of two types of co-receptors , CD4 and CD8 . These two cell types, called CD4+ and CD8+, respectively, have different and interacting cytotoxic effects. Therapies employing

4674-468: The early 2010s using second generation CARs targeting CD19 , a protein expressed by normal B cells as well as B-cell leukemias and lymphomas , by investigators at the NCI , University of Pennsylvania , and Memorial Sloan Kettering Cancer Center demonstrated the clinical efficacy of CAR T cell therapies and resulted in complete remissions in many heavily pre-treated patients. These trials ultimately led in

4756-598: The early part of the 20th century, and funded many new Seattle companies and products. In 1907, 19-year-old James E. Casey borrowed $ 100 from a friend and founded the American Messenger Company (later UPS ). Other Seattle companies founded during this period include Nordstrom and Eddie Bauer . Seattle brought in the Olmsted Brothers landscape architecture firm to design a system of parks and boulevards. The Gold Rush era culminated in

4838-486: The early years of the city, rode on the lumber industry. During this period the road now known as Yesler Way won the nickname "Skid Road", supposedly after the timber skidding down the hill to Henry Yesler 's sawmill. The later dereliction of the area may be a possible origin for the term which later entered the wider American lexicon as Skid Row . Like much of the U.S. West , Seattle experienced conflicts between labor and management and ethnic tensions that culminated in

4920-513: The first plats for the village were filed. In 1855, nominal land settlements were established. On January 14, 1865, the Legislature of Territorial Washington incorporated the Town of Seattle with a board of trustees managing the city. The Town of Seattle was disincorporated on January 18, 1867, and remained a mere precinct of King County until late 1869, when a new petition was filed and the city

5002-411: The growth strongly skewed toward the center of the city, and unemployment dropped from roughly 9 percent to 3.6 percent. The city has found itself "bursting at the seams", with over 45,000 households spending more than half their income on housing and at least 2,800 people homeless , and with the country's sixth-worst rush-hour traffic. Seattle is located between the saltwater Puget Sound (an arm of

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5084-401: The hilliest areas are near the city center, with Capitol Hill, First Hill, and Beacon Hill collectively constituting something of a ridge along an isthmus between Elliott Bay and Lake Washington. The break in the ridge between First Hill and Beacon Hill is man-made, a result of two of the many regrading projects that reshaped the topography of the city center. The topography of the city center

5166-550: The introduction of the engineered CAR T-cells. The depletion of the number of circulating leukocytes in the patient upregulates the number of cytokines that are produced and reduces competition for resources, which helps to promote the expansion of the engineered CAR T-cells. As of March 2019, there were around 364 ongoing clinical trials happening globally involving CAR T cells. The majority of those trials target blood cancers: CAR T therapies account for more than half of all trials for hematological malignancies. CD19 continues to be

5248-418: The last person leaving Seattle – Turn out the lights." Seattle remained the corporate headquarters of Boeing until 2001, when the company separated its headquarters from its major production facilities; the headquarters were moved to Chicago. The Seattle area is still home to Boeing's Renton narrow-body plant and Everett wide-body plant . The company's credit union for employees, BECU , remains based in

5330-425: The late 19th and early 20th centuries were almost entirely from Guangdong Province . The Seattle area is also home to a large Vietnamese population of more than 55,000 residents, as well as over 30,000 Somali immigrants. The Seattle-Tacoma area is also home to one of the largest Cambodian communities in the United States, numbering about 19,000 Cambodian Americans, and one of the largest Samoan communities in

5412-490: The mainland U.S., with over 15,000 people having Samoan ancestry. Additionally, the Seattle area had the highest percentage of self-identified mixed-race people of any large metropolitan area in the United States, according to the 2000 United States Census Bureau. According to a 2012 HistoryLink study, Seattle's 98118 ZIP code (in the Columbia City neighborhood) was one of the most diverse ZIP Code Tabulation Areas in

5494-620: The miners in Alaska and the Yukon . Few of those working men found lasting wealth. However, it was Seattle's business of clothing the miners and feeding them salmon that panned out in the long run. Along with Seattle, other cities like Everett , Tacoma , Port Townsend , Bremerton , and Olympia , all in the Puget Sound region, became competitors for exchange, rather than mother lodes for extraction, of precious metals. The boom lasted into

5576-439: The most popular antigen target, followed by BCMA (commonly expressed in multiple myeloma ). In 2016, studies began to explore the viability of other antigens, such as CD20. Trials for solid tumors are less dominated by CAR T, with about half of cell therapy-based trials involving other platforms such as NK cells . T cells are genetically engineered to express chimeric antigen receptors specifically directed toward antigens on

5658-462: The organization adopt its longtime local nickname, "Fred Hutch", as its official name as part of a rebranding. On April 1, 2022, Fred Hutchinson Cancer Research Center and Seattle Cancer Care Alliance (SCCA) merged to form Fred Hutchinson Cancer Center , a unified adult cancer research and care center that is clinically integrated with University of Washington (UW) Medicine and UW Medicine's cancer program. The center has employed three recipients of

5740-411: The population, Spanish was spoken by 4.5% of the population, speakers of other Indo-European languages made up 3.9%, and speakers of other languages made up 2.5%. Seattle's foreign-born population grew 40% between the 1990 and 2000 censuses. The Chinese population in the Seattle area has origins in mainland China , Hong Kong, Southeast Asia, and Taiwan . The earliest Chinese-Americans that came in

5822-586: The production of Boeing aircraft. The war dispersed the city's numerous Japanese-American businessmen due to the Japanese American internment . After the World War II, however, the local economy dipped. It rose again with Boeing's growing dominance in the commercial airliner market. Seattle celebrated its restored prosperity and made a bid for world recognition with the Century 21 Exposition ,

5904-531: The way to their claim passed three scouts of the Denny Party. Members of the Denny Party claimed land on Alki Point on September 28, 1851. The rest of the Denny Party set sail on the schooner Exact from Portland , Oregon, stopping in Astoria , and landed at Alki Point during a rainstorm on November 13, 1851. After a difficult winter, most of the Denny Party relocated across Elliott Bay and claimed land

5986-484: Was abandoned and its residents moved across the bay to join the rest of the settlers. David Swinson "Doc" Maynard , one of the founders of Duwamps, was the primary advocate to name the settlement Seattle after Chief Seattle ( Lushootseed : siʔaɫ , anglicized as "Seattle"), chief of the Duwamish and Suquamish tribes. The name "Seattle" appears on official Washington Territory papers dated May 23, 1853, when

6068-754: Was also changed by the construction of a seawall and the artificial Harbor Island (completed 1909) at the mouth of the city's industrial Duwamish Waterway , the terminus of the Green River . The highest point within city limits is at High Point in West Seattle, which is located near 35th Ave SW and SW Myrtle St. North of the city center, the Lake Washington Ship Canal connects Puget Sound to Lake Washington. It incorporates four natural bodies of water: Lake Union , Salmon Bay , Portage Bay , and Union Bay . Due to its location in

6150-492: Was appointed as the fourth President, following the retirement of Lee Hartwell . He was followed by Gary Gilliland in 2015 as president, who led the institute until 2020. Under his leadership the center announced that it would expand into the former Lake Union steam plant, which previously housed ZymoGenetics . The move was completed in October 2020. In February 2020, Thomas J. Lynch Jr. took over as director. The year 2014 saw

6232-478: Was founded in the immediate wake of the fire. The Panic of 1893 hit Seattle hard. The second and most dramatic boom resulted from the Klondike Gold Rush , which ended the depression that had begun with the Panic of 1893 . In a short time, Seattle became a major transportation center. On July 14, 1897, the S.S. Portland docked with its famed "ton of gold", and Seattle became the main transport and supply point for

6314-730: Was mildly prosperous in the 1920s but was particularly hard hit in the Great Depression, experiencing some of the country's harshest labor strife in that era. Violence during the Maritime Strike of 1934 cost Seattle much of its maritime traffic, which was rerouted to the Port of Los Angeles . The Great Depression in Seattle affected many minority groups, one being the Asian Pacific Americans; they were subject to racism, loss of property, and failed claims of unemployment due to citizenship status. Seattle

6396-497: Was one of the major cities that benefited from programs such as the Works Progress Administration , CCC , Public Works Administration , and others. The workers, mostly men, built roads, parks, dams, schools, railroads, bridges, docks, and even historical and archival record sites and buildings. Seattle faced significant unemployment, loss of lumber and construction industries as Los Angeles prevailed as

6478-448: Was one of the whitest big cities in the country, although its proportion of white residents has been gradually declining. In 1960, whites constituted 91.6% of the city's population, while in 2010 they constituted 69.5%. According to the 2006–2008 American Community Survey , approximately 78.9% of residents over the age of five spoke only English at home. Those who spoke Asian languages other than Indo-European languages made up 10.2% of

6560-687: Was re-incorporated December 2, 1869, with a mayor–council government . The corporate seal of the City of Seattle carries the date "1869" and a likeness of Chief Seattle in left profile. That same year, Seattle acquired the epithet of the "Queen City", a designation officially changed in 1982 to the "Emerald City". Seattle has a history of boom-and-bust cycles, like many other cities near areas of extensive natural and mineral resources. Seattle has risen several times economically, then gone into precipitous decline, but it has typically used those periods to rebuild solid infrastructure. The first such boom, covering

6642-535: Was set to outgrow. A site in the South Lake Union neighborhood, envisioned by the city as a future high-tech and biotechnology hub, was chosen in September 1988 after a deal to move to Fremont fell through earlier that year. The first phase of the campus, designed by firm Zimmer Gunsul Frasca Partnership , began construction in 1991 and opened on June 1, 1993, in a ceremony that included the burying of

6724-641: Was the first European to visit the Seattle area during his 1791–1795 expedition for the Royal Navy , which sought to chart the Pacific Northwest for the British. In 1851, a large party of American pioneers led by Luther Collins made a location on land at the mouth of the Duwamish River ; they formally claimed it on September 14, 1851. Thirteen days later, members of the Collins Party on

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