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Rkmatters

04/18/16 5:13 PM

#59249 RE: flipper44 #59244

Hi Flip,

You may want to look into the other studies presented at AACR using Adaptive’s immunosequencing platform and what the findings reveal. Skeptics would need to refute 10 studies it seems.

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Adaptive Biotechnologies and Collaborators to Present 10 Studies Demonstrating the Utility of Immunosequencing in Both Tissue and Blood Samples at 2016 American Association of Cancer Research Annual Meeting Posted on 2016-04-16
NEW ORLEANS–(BUSINESS WIRE)–Adaptive Biotechnologies, the leader in combining next generation sequencing (NGS) and expert bioinformatics to profile T- and B-cell receptors of the adaptive immune system, along with its collaborators
from institutions around the world, will present data demonstrating how Adaptive’s immunosequencing platform can be used as a novel oncology diagnostic to accurately and reliably quantify the density and clonality of Tumor Infiltrating Lymphocytes (TILs) to assess disease prognosis and response to therapy. Two oral presentations and eight posters will be presented at the American Association for Cancer Research (AACR) Annual Meeting, April 16-20, 2016, in New Orleans, Louisiana.

Notably, many of the data to be presented explore the relevance of the immune repertoire in the blood as well as in the tumor tissue. The potential to identify blood-based immune molecular biomarkers of response to the growing class of immunomodulatory drugs may offer clinicians a more accessible sample source for widespread benefit to patients across many tumor types.

Select data presentations of interest include:

Dr. Robert Prins, et al. from UCLA will present data showing that in patients with glioblastoma undergoing immunotherapy, immunosequencing
identified a potential biomarker of response and overall survival (Abstract 767).

Dr. Padmanee Sharma, et al. from MD Anderson Cancer Center will present data from a prostate cancer patient cohort receiving ipilimumab and androgen deprivation therapy correlating immune profiling data with adverse events which led to discovery of a potential predictive biomarker of patients who are at risk of grade 3 toxicities. (Abstract1402).

Dr. Rebecca Gardner, et al. from Seattle Children’s Research Institute will present data on children with acute lymphoblastic leukemia (ALL)
treated with a CART-19 therapy showing that high-throughput sequencing of patient samples had significantly greater sensitivity in detecting minimal residual disease (MRD) compared with samples analyzed by flow cytometry. Furthermore, in these patients, monitoring disease status by peripheral blood sampling is often more informative and far less invasive than bone marrow sampling. (Abstract 4893).

“These data being presented at AACR demonstrate the utility of immunosequencing in both tissue and blood samples as a critical component in guiding clinicians’ approach to managing and treating cancer,” said Harlan Robins, Chief Scientific Officer and Co-Founder of Adaptive Biotechnologies. “Ultimately incorporating immunosequencing into a potential blood-based biomarker for use in the clinic may help enhance the diagnosis, prognosis and monitoring of disease in cancer patients.”

Representatives from Adaptive Biotechnologies will be exhibiting at AACR booth #2530 to answer questions about their proprietary, transformative
immunosequencing technology.

Oral Presentations:

Abstract #847: Molecular characterization of breast tumor T-cell infiltration in exome datasets

Date and Time: Sunday, Apr 17, 2016, 4:35 PM – 4:50 PM
Location:
Room 243, Morial Convention Center
Presenter: Ricardo Armisen,
Universidad de Chile, Santiago, Chile

Abstract #4362: T cell repertoire diversification is associated with immune related toxicities following immune checkpoint inhibition in metastatic
cancer patients

Date and Time: Tuesday, Apr 19, 2016, 3:50 PM – 4:05 PM
Location:
New Orleans Theater C, Morial Convention Center
Presenter: Lawrence
Fong, University of California, San Francisco

Posters:

Abstract #767: TCR sequencing can identify and track tumor-specific T cell populations and is a predictive biomarker of response to DC vaccination
in glioblastoma patients

Date and Time: Sunday, Apr 17, 2016, 1:00 PM – 5:00 PM
Location:
Section 33, Poster Board #26
Author: Robert Prins, et al.,
University of California, Los Angeles

Abstract #1402: Exploratory biomarkers that predict for clinical outcomes in a Phase II trial with ipilimumab plus finite androgen deprivation therapy
for metastatic non-castrate prostate cancer

Date and Time: Monday, Apr 18, 2016, 8:00 AM – 12:00 PM
Location:
Section 22, Poster Board #3
Author: Padmanee Sharma, et al., The
University of Texas MD Anderson Cancer Center

Abstract #1405: Vesigenurtacel-L stimulates tumor infiltration of unique polyclonal T cell clones in non-muscle invasive bladder cancer patients

Date and Time: Monday, Apr 18, 2016, 8:00 AM – 12:00 PM
Location:
Section 22, Poster Board #6
Author: Melissa Price, et al., Heat
Biologics, Inc., Durham, NC

Abstract #2392: Genomic and immune heterogeneity in synchronous melanoma
metastases is associated with differential tumor growth and response totherapy

Date and Time: Monday, Apr 18, 2016, 1:00 PM – 5:00 PM
Location:
Section 28, Poster Board #22
Author: Jennifer A. Wargo, et al., MD
Anderson Cancer Center, Houston, TX

Abstract #4159: Characterization of the T-cell receptor (TCR) repertoire in extensive disease small cell lung cancer (ED SCLC)

Date and Time: Tuesday, Apr 19, 2016, 1:00 PM – 5:00 PM
Location:
Section 31, Poster board #26
Author: Cory Batenchuk, et al.,
Bristol-Myers Squibb, NJ

Abstract #4903: Multimodal therapy with a potent vaccine, metronomic cyclophosphamide and anti-PD-1 enhances immunotherapy of advanced tumors
by increasing activation and clonal expansion of tumor infiltrating T cells

Date and Time: Wednesday, Apr 20, 2016, 7:30 AM – 11:00 AM
Location:
Section 23, Poster board #14
Author: Genevieve Weir, et al.,
Immunovaccine, Inc., Halifax, NS, Canada

Abstract #4893: Molecular detection of ALL in the peripheral blood is more sensitive than flow cytometric analysis of the bone marrow in patients
with treatment-related hypocellularity

Date and Time: Wednesday, Apr 20, 2016, 8:00 AM – 12:00 PM
Location:
Section 23, Poster board #4
Author: Rebecca Gardner, et al.,
Seattle Children’s Research Institute, Seattle, WA

Abstract #4897: First evidence of changes in the TCRß repertoire from a cutaneous
melanoma patient immunized with the CSF-470 vaccine

Date and Time: Wednesday, Apr 20, 2016, 8:00 AM – 12:00 PM
Location:
Section 23, Poster board #8
Author: José Mordoh, et al., Centro de
Investigaciones Oncológicas-Fundación Cáncer, Ciudad Autónoma de Buenos
Aires, Argentina

About the immunoSEQ® Platform

Adaptive’s immunoSEQ Platform helps researchers make discoveries in areas such as oncology, autoimmune disorders, infectious diseases and
basic immunology. The immunoSEQ Assays can identify millions of T- and B-cell receptors from a single sample in exquisite detail. Offered as a
Service or Kit, immunoSEQ Assays provide quantitative, reproducible sequencing results along with access to powerful, easy-to-use analysis tools. The immunoSEQ Assays are for research use only and are not for use in diagnostic procedures.

About Minimal Residual Disease

Minimal residual disease (MRD) refers to cancer cells that may remain in the body of a person with lymphoid cancer after treatment. These cells are present at levels undetectable by traditional microscopic examination (also called morphologic examination) of blood, bone marrow or a lymph node biopsy. Sensitive molecular technologies, such as the next-generation sequencing utilized by Adaptive’s clonoSEQ MRD Test, are
needed for reliable detection of very low levels of MRD. Learn more at knowMRD.com.

About the clonoSEQ® Process

Adaptive’s clonoSEQ Process enables physicians to utilize sequencing-based minimal residual disease (MRD) detection as an aid to clinical decision making for patients with lymphoid cancers (blood cancers). With its ability to detect cancer cells at a level as low as
one per one million white blood cells, the clonoSEQ MRD Test is one to two orders of magnitude more sensitive than the other methods of MRD detection, such as ASO-PCR and flow cytometry.

About Adaptive Biotechnologies®

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. For more information please visit adaptivebiotech.com.

Doc logic

04/18/16 11:19 PM

#59262 RE: flipper44 #59244

flipper44,

TILs can include M2 macrophages and T regulator cells as well to varying degrees. These are immunosuppressive as is the hypoxic environment where many cancer stem cells are conserved. Unprimed DCs do not regulate M2 macrophages or Tregs well because they do not initiate a strong enough immune signaling response or one that is long enough to overcome it's weaker response to inflammatory signaling they initially responded to. They can not stay in this tumor environment for very long and also meet immunosuppressive resistance to at the tumor draining lymph nodes when they manage to migrate there with antigen presenting capacity. In total, this prevents a "highly educated" and motivated immune response even when educated TILs are present because critical targets are in a submerged position unless and until a sufficient immune inflammatory response is created.