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Seattle, WA, United States

Weng W.-K.,Stanford University | Armstrong R.,Stanford University | Arai S.,Stanford University | Desmarais C.,Adaptive Biotechnologies | And 2 more authors.
Science Translational Medicine | Year: 2013

Mycosis fungoides (MF) and the leukemic presentation Sézary syndrome (SS) are clonal T cell lymphomas arising from the skin and are considered noncurable with standard therapies. To develop a specific and sensitive monitoring tool, we tested the ability of high-throughput sequencing (HTS) of T cell receptors (TCRB) to monitor minimal residual disease (MRD) after allogeneic hematopoietic cell transplantation. Genomic DNA was extracted from peripheral blood mononuclear cells (PBMCs) or skin samples. The rearranged TCRb loci were amplified using Vβ- and Jβ-specific primers, followed by HTS, to generate up to 1,000,000 reads spanning the CDR3 region of individual cells. Malignant clones were identified in diagnostic samples in all cases by a dominant CDR3 sequence. Before transplant, four patients had circulating Sézary cells by the routine flow cytometry, which was confirmed by TCRB HTS. Although the flow cytometry found no detectable Sézary cells, malignant clones were detected by TCRB HTS in all other six cases. Five patients achieved "molecular remission" in blood between +30 and +540 days after transplant. Four of these patients also achieved molecular clearance in skin after transplant. Experiments using blood samples spiked with purified Sézary cells demonstrated that TCRB HTS can detect Sézary cells at the level of 1 in 50,000 PBMCs, which is more sensitive than standard diagnostics. We have thus demonstrated the utility of TCRB HTS to assess MRD with increased sensitivity and specificity compared to other current methodologies, and to monitor response to therapy in this MF/SS patient population. Source


SEATTLE--(BUSINESS WIRE)--Adaptive Biotechnologies, the leader in combining next-generation sequencing and expert bioinformatics to profile T-cell and B-cell receptors (TCRs and BCRs) of the adaptive immune system, today published a study detailing a powerful new tool that enables sensitive and quantitative monitoring of T cells specific for hundreds, and possibly thousands, of antigens simultaneously and in a single experiment. “Immunosequencing allows sensitive and quantitative detection of all T and B cells in a sample and has allowed many new insights into the immune system. However, it does not provide information about antigen specificity,” said Malek Faham, M.D., Ph.D. Senior Vice President, Innovation at Adaptive Biotechnologies, and senior author of the study. “This approach extends the power of immunosequencing by allowing precise identification of T cells specific to large numbers of antigens.” Previous work demonstrated the ability to combine conventional immune monitoring assays, which enable identification of populations of T cells that either bind to or respond to antigens, with immunosequencing to identify T cells specific to one particular antigen. This new study builds upon these results by pooling multiple antigens together in different combinations. The number of antigens that can be assessed in a single experiment increases exponentially with the number of pools created. The high sensitivity of the assay allows antigen-specific T cells to be detected at frequencies as low as one per million total T cells. "With this new multiplex technology we now have the ability to assign antigen-specificity to TCR sequences at a massive scale,” said Harlan Robins, Ph.D., Chief Scientific Officer and Co-Founder at Adaptive Biotechnologies. “Combined with our first-in-class technology for pairing TCR alpha and beta chain sequences at high throughput, we now have the tools needed for efficient identification of functional immune receptors, which may lead to tremendous advancements in biomarker discovery and therapeutic development." The study, “Multiplex Identification of Antigen-Specific T Cell Receptors Using a Combination of Immune Assays and Immune Receptor Sequencing,” by Klinger, et al. was published online today in PLOS ONE. Adaptive Biotechnologies is the pioneer and leader in combining high-throughput sequencing and expert bioinformatics to profile T-cell and B-cell receptors. Adaptive is bringing the accuracy and sensitivity of its immunosequencing platform into laboratories around the world to drive groundbreaking research in cancer and other immune-mediated diseases. Adaptive also translates immunosequencing discoveries into clinical diagnostics and therapeutic development to improve patient care.


SEATTLE--(BUSINESS WIRE)--Adaptive Biotechnologies, the leader in combining next-generation sequencing and expert bioinformatics to profile T-cell and B-cell receptors (TCRs and BCRs) of the adaptive immune system, today published a study detailing a powerful new tool that enables sensitive and quantitative monitoring of T cells specific for hundreds, and possibly thousands, of antigens simultaneously and in a single experiment. “Immunosequencing allows sensitive and quantitative detection of all T and B cells in a sample and has allowed many new insights into the immune system. However, it does not provide information about antigen specificity,” said Malek Faham, M.D., Ph.D. Senior Vice President, Innovation at Adaptive Biotechnologies, and senior author of the study. “This approach extends the power of immunosequencing by allowing precise identification of T cells specific to large numbers of antigens.” Previous work demonstrated the ability to combine conventional immune monitoring assays, which enable identification of populations of T cells that either bind to or respond to antigens, with immunosequencing to identify T cells specific to one particular antigen. This new study builds upon these results by pooling multiple antigens together in different combinations. The number of antigens that can be assessed in a single experiment increases exponentially with the number of pools created. The high sensitivity of the assay allows antigen-specific T cells to be detected at frequencies as low as one per million total T cells. "With this new multiplex technology we now have the ability to assign antigen-specificity to TCR sequences at a massive scale,” said Harlan Robins, Ph.D., Chief Scientific Officer and Co-Founder at Adaptive Biotechnologies. “Combined with our first-in-class technology for pairing TCR alpha and beta chain sequences at high throughput, we now have the tools needed for efficient identification of functional immune receptors, which may lead to tremendous advancements in biomarker discovery and therapeutic development." The study, “Multiplex Identification of Antigen-Specific T Cell Receptors Using a Combination of Immune Assays and Immune Receptor Sequencing,” by Klinger, et al. was published online today in PLOS ONE. Adaptive Biotechnologies is the pioneer and leader in combining high-throughput sequencing and expert bioinformatics to profile T-cell and B-cell receptors. Adaptive is bringing the accuracy and sensitivity of its immunosequencing platform into laboratories around the world to drive groundbreaking research in cancer and other immune-mediated diseases. Adaptive also translates immunosequencing discoveries into clinical diagnostics and therapeutic development to improve patient care.


SEATTLE--(BUSINESS WIRE)--Goldman Sachs (NYSE:GS) is recognizing Adaptive Biotechnologies’ Chad Robins, President, Chief Executive Officer and Co-Founder, and Harlan Robins, Chief Scientific Officer and Co-Founder, as part of the 100 Most Intriguing Entrepreneurs of 2015 at its Builders + Innovators Summit in Santa Barbara, California. Goldman Sachs selected Chad and Harlan Robins as part of 100 entrepreneurs from multiple industries to be honored at the two-day event. Brothers, Chad and Harlan Robins, built Adaptive Biotechnologies based on a ground-breaking technology platform that profiles the adaptive immune system and revolutionizes the way we discover, diagnose and treat diseases. It takes years of dedication and commitment to get a biotech company off the ground and finding success is often a futile effort. But not for an adventuresome entrepreneur with a keen business acumen and an innovative theoretical physicist with a passion for healthcare — together, with their ever-growing team, they have built the awareness of a novel tool while demonstrating its many applications in research, clinical and therapeutic contexts. Watch the Builders + Innovators video on Adaptive Biotechnologies: http://www.goldmansachs.com/our-thinking/technology-driving-innovation/builders-and-innovators-2015/index.html?videoId=109321 "It’s a privilege to be recognized among such innovative thinkers who have made such exciting advances in highly competitive industries." said Chad Robins. “It’s a massive team effort to get any company off the ground and to keep it growing at an ever-accelerating pace. The integrity, passion and dedication of those at Adaptive have been pivotal to our success as a company to date, and I am more convinced than ever of the transformative impact that Adaptive will have as we continue on our path to change the course of medicine.” "We are honored to recognize Chad and Harlan Robins as part of the most intriguing entrepreneurs of 2015," said David Solomon, co-head of investment banking at Goldman Sachs. "This is an exciting time for entrepreneurs. This is the fourth year that we’ve hosted the Builders + Innovators Summit and continue to be amazed by what happens when a diverse group of seasoned and emerging business leaders -- the builders and innovators – come together to discuss how to drive innovation, create jobs, and build enduring organizations." For more than 145 years, Goldman Sachs has been advising and financing entrepreneurs as they launch and grow their businesses. In addition to honoring 100 entrepreneurs, the summit consists of general sessions and clinics led by Goldman Sachs experts, seasoned entrepreneurs, academics and business leaders as well as resident scholars. Adaptive Biotechnologies is the pioneer and leader in combining high-throughput sequencing and expert bioinformatics to profile T-cell and B-cell receptors. Adaptive is bringing the accuracy and sensitivity of its immunosequencing platform into laboratories around the world to drive groundbreaking research in cancer and other immune-mediated diseases. Adaptive also translates immunosequencing discoveries into clinical diagnostics and therapeutic development to improve patient care.


News Article | April 22, 2015
Site: www.geekwire.com

Every April, there was to be a show of symmetry in Washington state. This month, Big Tobacco made its annual delivery of millions of dollars to the state, a cash infusion that springs from a legal settlement. Until 2009, a substantial portion of this money was allocated to the Life Sciences Discovery Fund, which finances medical research and helps researchers from University of Washington, Fred Hutch, and other institutions bring their work to market. Money from an unhealthy product would create a healthier world, or so the concept went. Instead, the Life Sciences Discovery Fund has become a poster child for Olympia’s frequent inability to fund valuable programs. That’s despite its generation of more than $1 billion in economic activity, creating thousands of jobs, and boasting of a seven-to-one return on investment. For the second year in a row, the state Senate has voted to axe all financing for the LSDF, siphoning its allocated funding into the state’s general coffers. Should the Republican-backed proposal make it into final 2015-2017 operating budget, the fund would effectively be eliminated by June 30, as would the 46 in-progress research studies it currently supports. These include a new drug to treat Parkinson’s disease, treatments for a variety of cancers, a blood test to detect Alzheimer’s earlier and many other projects. “If we were to be fully funded under our original legislation, we’d be receiving $26 million when the check from Big Tobacco comes on April 15,” says John DesRosier, executive director of LSDF. “Instead, we’re looking at the possibility of closing down.” That the state Legislature would treat LSDF as a piggy bank is nothing new. When the recession hit in 2009, the program was slashed to raise cash for the general fund. While the fund’s annual budget was about $33 million before the recession, it is now less than $10 million per year. While the legislature’s previous actions could be seen as a dip into the piggy bank, the Senate’s recent proposals represent smashing it open with a hammer. When a full defunding of LSDF was proposed last year, the media and other organizations across the state took note, and a veto from Gov. Jay Inslee saved the program from extermination. This year, the defunding plan has flown more under the radar, and Inslee will not have the same option. In a statement to Crosscut, Inslee’s office notes that “the governor does not have the tool he had last year to save this. Last year the governor vetoed a section that would have cancelled [the program]. The problem this year is that if the final legislative budget does not include a section providing funding for Life Science Discovery Fund, we can’t put something in via veto.” DesRosier is unfailingly polite when discussing Olympia’s process, but can’t contain his frustration that a financially successful program must fight for its life year after year. If we were to be fully funded under our original legislation, we’d be receiving $26 million when the check from Big Tobacco comes on April 15 Instead, we’re looking at the possibility of closing down. “When I speak with legislators on the R side, they’re almost uniformly saying, ‘You guys are doing good work. The payoffs are good. The return is good.’ But then there’s always a ‘but’ — ‘But we’re trying to fill a budget hole.’” Repeated requests for comment from members of the Senate GOP —  including budget lead Sen. Andy Hill and Sen. Ann Rivers, who sits on the LSDF board — were unsuccessful. The main value of LSDF is in bringing research across the “Valley of Death,” as it’s sometimes known.  Washington institutions like UW are excellent at attracting federal grants for research. However, once researchers wish to take their work to market, and possibly start a business, federal funding tapers off. With private sector backers increasingly risk adverse and unwilling to bank on projects that aren’t fully fleshed out, this leaves many researchers unable to reach the next step, or “cross the valley.” An example of how some modest support can make a difference is Seattle-based Adaptive Biotechnologies. When LSDF funded them, DesRosier says, they had four employees, and were struggling to find investors. Now they’re up to about 80, with plans to double that number in the near future. “If you’re trying to grow the job base and the tax base, you have to look at the long game,” says DesRosier. “We want people to bring us their best ideas. The problem is when your funding fluctuates, people might take a step backwards. … This climate creates uncertainty that can be really detrimental.” In a statement, the governor’s office agreed, saying that defunding LSDF and canceling projects that have years of work behind them “would reflect extremely poorly on the state of Washington.” Whether the Senate’s proposal reaches the final operating budget, Washington’s position as  a leader in the life science industry is not without its challengers. States such as Pennsylvania, Indiana, Texas, California, and Massachusetts are investing to grow the sector as part of their economic development strategy.

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