Immunotherapy Takes the Stage
As recently as five years ago, immunologists and oncologists were not close colleagues. Any immune work at a cancer conference happened off to the side and out of the limelight, almost an afterthought. Much like the kids table at Thanksgiving dinner, these collaborations were recognized, but not taken seriously. However, the 2016 American Association of Cancer Research (AACR) meeting in New Orleans could have easily been mistaken for an immunology symposium. Posters and presentations outlined all the latest findings on checkpoint inhibitors, CAR T cells, and combination immunotherapies. Even Vice President Joe Biden, who took the stage at the close of the meeting, acknowledged that immunology had taken its rightful place at the forefront of cancer research. However, the Vice President also highlighted a major hurdle that still plagues the burgeoning immunotherapy field: why do some patients respond favorably to immunotherapies while others fail to respond?
Adaptive Biotechnologies has been working to answer this very question since spinning its T-cell receptor sequencing technology out of the Fred Hutchinson Cancer Research Center in 2009 . With its immunoSEQ® Platform, Adaptive is at the leading edge of immune repertoire profiling by applying high throughput sequencing and expert bioinformatics to profile T-and B-cell receptors, which is rapidly becoming the method of choice to determine mechanisms of action, predict adverse events , and monitor responses to various treatment modalities [4-5].
A prime example of the immunoSEQ technology being used to enhance immunotherapy research was recently published in Cancer Immunology Research and showcased at AACR by the lab of Robert Prins at UCLA . The Prins lab developed a dendritic cell (DC) vaccine to improve treatment of patients with glioblastoma multiforme (GBM), a brain cancer with a median survival of only about 12 months. DCs are specialized antigen presenting cells capable of igniting an anti-tumor immune response by presenting tumor proteins to cytotoxic T cells. Using tumor biopsies from each patient, Prins, et al. were able to load DCs with proteins from the actual tumor. The DCs were then transfused back into the patient with the hope that they would induce a potent anti-tumor T-cell response against the glioblastoma.
The individual patient responses varied, with some patients surviving only a few months post treatment and others well exceeding the 12 month median. This led the investigators to ask a very similar question to that which Vice President Biden posed during his address to the AACR attendees: why was there variability in response to this vaccine?  The Prins group believed the answer would be found in each patient’s individual immune response, and they were interested in how their vaccine might shape each patient’s T-cell repertoire.
Using the Adaptive immunoSEQ Assay, the researchers identified and quantified the pre-existing tumor infiltrating T-cell (TIL) clones in each GBM tumor and compared them to the clones circulating in the patient’s blood, pre- and post-vaccination. The results were striking. The overlap of each patient’s TIL and blood T-cell repertoire pre-treatment directly correlated with patient survival. Patients with low TIL-to-blood overlap had the poorest response to the vaccine. Conversely, those patients with high overlap showed persistent T-cells responses and longer overall survival. For one patient this equated to nearly six additional years of life.
These data strongly emphasize the importance of understanding and monitoring T-cell response in patients receiving immunotherapies. There are countless examples from top labs across the globe of T-cell monitoring being able to predict response to treatment and, as this field continues to drive forward at unprecedented speed, the need for immunosequencing will continue to expand. Adaptive Biotechnologies is committed to establishing immunosequencing as a critical component for all immuno-oncology investigation and is dedicated to advancing cancer research to the point where every patient can one day receive truly personalized therapy.
 Comprehensive assessment of T-cell receptor beta-chain diversity in alphabeta T cells, Robins et al., Blood, Nov 2009
 PD-1 blockade induces responses by inhibiting adaptive immune resistance, Tumeh et al., Nature, Nov 2014
 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, Subudhi et al., Poster Presentation AACR, Apr 2016
 Genomic and immune heterogeneity in synchronous melanoma metastases is associated with differential tumor growth and response to therapy, Reuben et al, Poster Presentation, Apr. 2016
 BRAF inhibition is associated with increased clonality in tumor-infiltrating lymphocytes, Cooper et al., Oncoimmunology, Oct. 2013
 TCR sequencing can identify and track glioma-infiltrating T cells after DC vaccination, Hsu MS, et al, Cancer Immunology Research, Mar. 2016
 VP Joe Biden’s Speech at the AACR 2016 Annual Meeting in New Orleans