ImmunoSEQ by Adaptive Biotechnologies

Adaptive Biotech joins Obliteride, show your support as well!

cdesmarais — Fri, 17 May 2013 19:24:04 +0000

Here at Adaptive, the fight against cancer is part of what motivates us and gives us a good bit of daily satisfaction with our work. This is why we are proud to support the Fred Hutchinson Cancer Research Center’s Obliteride Campaign. Research is the fastest way to end cancer, and we are fortunate to have FHCRC, one of the top cancer research institutes in the world, right here in our community. Everyday, scientists are inspired by the hope of finding the next big breakthrough that may lead to cancer cures. That being said, government funding has been flat in recent years, making the need for donations more important than ever. Every dollar raised with this event will go towards cancer research at FHCRC.

To this same end, we’ve rallied around the Obliteride campaign to fight cancer. We ride to find a cure, to end cancer, for our family and friends who have fought or are fighting cancer. Who or what will you ride for?

Lest you think we’re simply saints, the rumor has it that road cycling is the “golf” of biotech in the Seattle, San Diego and SF bay area. Apparently this bit of industry culture is not exclusive to the United States.

So whatever your reasons, join us in August on the road!

New Cancer Drugs Harness Power of Immune System

cdesmarais — Thu, 16 May 2013 23:36:17 +0000

Yesterday, the Wall Street Journal addressed two early stage drug studies- one from Bristrol-Myers Squibb and one from Roche Holding AG. Both drug studies rely on the power of the patients’ immune system to fight the cancer they have been diagnosed with.

Bristol-Meyers used a two drug combination treatment on skin cancer patients, in which nearly a third of patients experienced “rapid and deep tumor regressions”. One of the drugs used in the combination is Yervoy, which is already on the market. The second drug is nivolumab, an experimental drug. Together, the drugs were more highly effective than when administered alone.

Whereas Bristol-Meyers used a combination, the Roche study used a single agent known as MPDL3280A. 21% of tumors responded and a little less than 21% of the tumors did not progress.

The full article can be read here.

Adaptive CLIA licensed and preparing to receive clinical samples

cdesmarais — Wed, 15 May 2013 23:05:10 +0000

We are proud to announce that Adaptive Biotechnologies successfully passed its recent CLIA audit with no deficiencies. This accomplishment paves the way for final validation of the clonoSEQ clinical assays for the monitoring of minimal residual disease (MRD). ClonoSEQ is the most sensitive test available to detect MRD to assess effectiveness of treatments, monitor patient remission status, and personalize future treatments. The assays (TCRB, TCRG, and IgH) which target the V(D)J and DJ/VJ recombination in the CDR3 regions of the respective T and B cell receptors will soon be available for clinical use.

To be one of the first to be notified and to create an account, sign up for the clonoSEQ mailing list by emailing clonoSEQ@adaptivebiotech.com and visiting our website, www.clonoSEQ.com that has more details and FAQs. As always, feel free to contact Adaptive with questions or for additional information at (206) 659-0067 or toll free at (855) 466-8667 as well as by email at info@adaptivebiotech.com.

Where do you draw the line for minimal residual disease (MRD) determination?

cdesmarais — Mon, 13 May 2013 15:48:12 +0000

As chemotherapeutic treatment of patients with hematopoietic malignancies was emerging during the second half of the 20th century it became important to develop measurements and milestones of treatment efficacy. For decades the milestone of “remission” has included microscopic examination of a stained bone marrow specimen, and is defined as fewer than 5% residual leukemic blasts present in the bone marrow sample obtained from a patient at some point during or following his/her course of treatment. The 5% level was chosen because of the belief that this is, conservatively, the level of sensitivity of the eyes of a well-trained hematopathologist in being able to distinguish morphologically distinct leukemic lymphoblasts within the background of the normal cell lineages that comprise the marrow. Obviously, given sampling variation and the subjectivity of morphologic classification, the claim, based on this analysis, that a marrow demonstrates “remission” can be quite subjective and impossible to standardize.

Over the past 10-15 years multi-parametric flow cytometry has increased the sensitivity of residual disease detection by two-three logs. This approach utilizes a set of reagents recognizing distinctive cell surface markers on cells at different stages of hematopoietic development. Based on the distinctive combination of markers on the cell surface, malignant cells are identified and quantitated. The sensitivity of detection of multiparametric flow cytometry is 10-3-10-4. Different laboratories use different cocktails of reagents for phenotypic classification and the parameters that enable grouping of cells of interest into one or another phenotypic category are somewhat technician dependent. In addition, the phenotype of the malignant cells may change over time in response to cellular evolution, treatment, or disease process, making problematic in some patients serial investigation of leukemic cell burden.

Over the past few years DNA-based approaches to lymphoid malignancy MRD determination have been developed. In these approaches it is the unique rearrangement of V, D, and J segments to create the contiguous V(D)J region of the immune receptor(s) carried by the malignant lymphocytes (immunoglobulin or T-cell receptor) that is used as a specific marker of the malignant clone. In one approach only the rearrangement in the leukemic cell is specifically amplified and characterized. This assay requires individualization of the assay for each specific patient. Adaptive Biotechnologies has developed an approach utilizing multiplex polymerase chain reaction (PCR) followed by high throughput sequencing in which the entire immune repertoire of immunoglobulin and/or T-cell receptors in any given bone marrow or blood sample is amplified and quantitated. At diagnosis the leukemic clone represents a disproportionate percentage of the overall repertoire and is therefore flagged for subsequent tracking. Each follow-up sample during the course of a patient’s treatment regimen is then analyzed with regard to the presence or absence of this diagnostic leukemic clone. This assay is not only more accurate than flow cytometry, it is more sensitive. If a sample containing a million cells is studied (a routine input for the Adaptive assay) the sensitivity of the assay is one leukemic cell in a million. It is also impervious to the phenotypic changes that can obscure the result by flow cytometry.

Previous work utilizing flow cytometry for MRD determination has demonstrated that it is possible to stratify patients into prognostic categories with regard to 5-year event free survival based on whether at the end of induction therapy their bone marrow still contains >1X10-2 leukemic cells (high risk), between 1X10-2 and 1X10-4 leukemic cells (intermediate risk), or <1X10-4 cells (standard risk). The increased sensitivity of the Adaptive assay has raised the question of what level of MRD is clinically impactful. To begin this consideration it should be pointed out that the cut-off at 10-4 was not based on biology but simply the level of sensitivity of flow cytometry. Similarly the focus on a time point at the end of induction was chosen empirically. The data from these studies to date provide a reasonable estimate of the early response of the leukemia to a given therapy and clearly, that has an impact on the overall prognosis for a patient. However, it is also clear that some patients with fewer than 1X10-4 residual leukemic cells post induction can and do still relapse, while some patients with greater than 10-4 residual leukemic cells are cured. Early response information, while very valuable, does not provide insight into the current biology or tempo of a particular patient’s leukemia. Might some or all of the cells that are detected at less than 10-4 be incapable of dividing and therefore of no clinical significance? Yes, but the same could be said for some of the cells noted that are above that somewhat arbitrary level. We can all agree that we would want for our patients to have the most dramatic initial response to therapy as possible (as low a level of residual leukemic cells that can be assessed) but we can only declare a cure with certainty if there are no leukemic cells left and no assay at present is capable of the total body evaluation that would be required to reach that conclusion. Our evaluation can be aided, however, by obtaining a sample from more than one time point (perhaps at the end of induction followed by a second sample at the end of consolidation) and comparing the values of residual disease over the course of a patient’s treatment. We can establish a trend (a trend may be evident even if both values are below the level of sensitivity of flow cytometry). We can identify relapse earlier, before it becomes clinically evident. We can also identify any newly emerging dominant clone in any sample of interest. It is also quite likely that the increased sensitivity of the Adaptive assay will allow for the sampling of peripheral blood for MRD determination as a complement to bone marrow examination which would make serial sampling much more practical and comfortable for both patient and provider.

Congrats to Adaptive Customer Dr. Carl June, Recipient of the SITC 2013 Richard V. Smalley, MD Memorial Award

cdesmarais — Fri, 10 May 2013 22:58:11 +0000

Yesterday, it was announced by SITC that Dr. Carl June would be receiving their most prestigious award at the Society’s Annual Meeting. In case you missed their email announcement, please see below. We are honored to be able to work with Dr. June and look forward to continuing out relationship with him as a customer!

Adaptive Partners with BMS on Cancer Immunotherapy Program

cdesmarais — Thu, 09 May 2013 23:27:31 +0000

Today, Adaptive announced a partnership with Bristol Myers Squibb for the discovery of immunological biomarkers in cancer. The announcement was even picked up by the Wall Street Journal, whose press release can be read here. BMS is a pioneer and leader in cancer immunotherapy, having launched ipilumimab (Yervoy), for melanoma in March 2011. Immunotherapy drugs target the immune system by activating protein receptors that regulate that the immune system. BMS is building on its leading franchise to test multiple new targets and combination regimens across many malignancies including, but not limited to, melanoma, non small cell lung cancer, and renal cell carcinoma.

BMS is using Adaptive’s proprietary technology to assess the impact of treatments on the immune system and as a potential tool to identify patient populations who might be more likely to respond to targeted therapies based on their immune status.

The announcement comes at a fortuitous time as the Cancer Research Institute (CRI) just declared June “Cancer Immunotherapy Awareness Month” to increase awareness of cancer immunotherapy, a new class of cancer treatment that mobilizes the immune system to fight the disease and represents the most immediate hope for curing patients with any type of cancer. Many members of the public are not aware of cancer immunotherapy’s ability to treat cancer and its potential to offer safer and more effective treatment options for all cancer patients.

Adaptive is extremely dedicated to cancer immunotherapy, committed to predicting patient response and understanding therapeutic efficacy and disease progression. The Company is working with leading clinicians and principal investigators in the field from top cancer centers including Memorial Sloan Kettering Cancer Center, MD Anderson, Dana Farber Cancer Institute and the Fred Hutchinson Cancer Research Center.

We are thrilled to embark on this milestone partnership.

Adaptive Clients Publish Latest Results in Nature- Now Available Online

cdesmarais — Thu, 09 May 2013 20:42:57 +0000

Yesterday, a team of researchers from the University of Washington, Fred Hutchinson Cancer Research Center and Benaroya Research Institute published results from a study in which they used the immunoSEQ assay to identify the immune cells that suppress genital herpes infections. The study resulted in the discovery of a subtype of immune cells, called CD8αα+ T cells, which could open a new avenue of research to develop a vaccine to prevent and treat HSV-2. The next step will be to identify these T cells’ specific molecular targets or epitopes.

The release of the paper has already sparked a few stories. Fred Hutch had a News Release, WebMD’s HealthDay News posted an article, redOrbit put out a story, and KUOW spoke about it this morning as well (article with accompanying audio can be found here).

The abstract is reprinted below. To obtain a copy of the publication, click here.

Nature . 2013 May 8.

Immune Surveillance by CD8aa+ Skin-Resident T Cells in Human Herpes Virus Infection

Jia Zhu, Tao Peng, Christine Johnston, Khamsone Phasouk, Angela S. Kask, Alexis Klock, Lei Jin, Kurt Diem, David M. Koelle, Anna Wald, Harlan Robins & Lawrence Corey

Source

Department of Laboratory Medicine, University of Washington, Seattle, WA, USA;

Abstract

Most herpes simplex virus 2 (HSV-2) reactivations in humans are subclinical and associated with rapid expansion and containment of virus. Previous studies have shown that CD8⁺ T cells persist in genital skin and mucosa at the dermal–epidermal junction (DEJ)—the portal of neuronal release of reactivating virus—for prolonged time periods after herpes lesions are cleared^1, 2. The phenotype and function of this persistent CD8⁺ T-cell population remain unknown. Here, using cell-type-specific laser capture microdissection, transcriptional profiling and T-cell antigen receptor β-chain (TCRβ) genotyping on sequential genital skin biopsies, we show that CD8αα⁺ T cells are the dominant resident population of DEJ CD8⁺ T cells that persist at the site of previous HSV-2 reactivation. CD8αα⁺ T cells located at the DEJ lack chemokine-receptor expression required for lymphocyte egress and recirculation, express gene signatures of T-cell activation and antiviral activity, and produce cytolytic granules during clinical and virological quiescent time periods. Sequencing of the TCR β-chain repertoire reveals that the DEJ CD8αα⁺ T cells are oligoclonal with diverse usage of TCR variable-β genes, which differ from those commonly described for mucosa-associated invariant T cells and natural killer T cells. Dominant clonotypes are shown to overlap among multiple recurrences over a period of two-and-a-half years. Episodes of rapid asymptomatic HSV-2 containment were also associated with a high CD8 effector-to-target ratio and focal enrichment of CD8αα⁺ T cells. These studies indicate that DEJ CD8αα⁺ T cells are tissue-resident cells that seem to have a fundamental role in immune surveillance and in initial containment of HSV-2 reactivation in human peripheral tissue. Elicitation of CD8αα⁺ T cells may be a critical component for developing effective vaccines against skin and mucosal infections.

DNA Extractions Simplified with New Device from UW Spinout Company NanoFacture

cdesmarais — Tue, 07 May 2013 23:14:12 +0000

Yesterday, Science Daily announced a cool new device that can extract human DNA with full genetic data in minutes. The device is box shaped and handheld, and can extract DNA from fluid samples. Now, extracting DNA can be as easy as swabbing your mouth for saliva and waiting a few minutes for the machine to work it’s magic.

An associate who led the research describes the current procedure of DNA extractions as “collecting human hairs using a construction crane” and proposes that this new invention will help to clear those hurdles. Microscopic probes dip into the fluid sample and apply an electric field within the liquid, which draws particle to concentrate around the surface of the probe. Larger particles hit the tip and swerve away, while DNA sized molecules stick to the probe and are trapped on the surface. Two to three minutes is all it takes to separate and purify DNA.

The device can do 4 samples at once, but the technology can be scaled to prep 96 samples at once.

For more info, the entire article can be read here.

Tumor Immune Suppression May Facilitate Targeted Radiation Treatment for Pancreatic Cancer

cdesmarais — Mon, 06 May 2013 15:34:10 +0000

Because pancreatic cancer is often diagnosed after it has spread to other organs, treatment through chemotherapy, surgery, and radiotherapy are generally ineffective. Five-year survival is estimated at less than 5%, with no significant improvements in therapy in recent decades. In a mouse model of pancreatic cancer, researchers at Albert Einstein College of Medicine in New York have leveraged the immunosuppressive properties of tumors to deliver targeted therapy via radioactive bacteria that persist in the suppressed environment. Their paper was recently published in PNAS and can be found here.

An attenuated form of the bacteria listeria was coupled to the radioisotope Rhenium-188 using listeria-binding antibodies. Given the efficiency with which the immune system clears listeria from normal tissue, the researchers were able to deliver safe doses of the radioactive listeria while therapeutic dose levels were attained at tumor sites due to the heavily immunosuppressive microenvironment of metastases and primary tumor. The treated mice presented 90% less metastases than control groups, a dramatic and encouraging result in an area that has seen little recent progress.

Nature news also covered a story on the research which can be read here.

The Cancer Genome Atlas Research Network Reports New Findings In Two Deadly Cancers

cdesmarais — Fri, 03 May 2013 18:49:53 +0000

This week, two papers by the Cancer Genome Atlas Project (TCGA) consortium characterized genomes and epigenomic landscapes of two cancers: endometrial carcinoma (Nature) and adult de-novo acute myeloid leukemia (New England Journal of Medicine). Both studies describe molecular subtypes of the diseases, a clinically actionable information that will hopefully soon translate into individual effective treatments.

As David P. Steensma pointed out in an accompanying editorial in the May 1 issue of NEJM, this work is a culmination of an 8-year effort of the TCGA consortium to catalog genetic changes in 10,000 cancer genomes. Despite being criticized as a costly exercise in piling up of terabytes of hard to interpret data, today’s matured bioinformatics have already demonstrated that clinically relevant information can indeed be extracted from these sequencing projects.

Particularly, the AML sequencing project has generated information with prognostic value (DNMT3A gene mutations) and the latest data will serve as a basis for research on the disease biology, tumor classification and patient risk stratification. Despite the fact that AML has the smallest number of mutations of all adult cancer types sequenced to date, the clonal architecture of AML is very complex, with clones evolving during the course of the disease and treatment.

These new findings make us at Adaptive Biotechnologies very excited, since we hope that our immunorepertoire assays will help to identify novel subtypes of the disease and complement the existing genomic and epigenomic data.

The new findings were also covered in a story in the LA Times, which can be read here.