Jun 29, 2017

Harnessing the therapeutic potential of adoptively transferred cells

Shauna Clark

Our recent Nature Webcast featured Dr. Aude Chapuis, professor and assistant member of the Clinical Research Division at the University of Washington and Fred Hutchinson Cancer Research Center, respectively, who spoke about "Harnessing the therapeutic potential of adoptively transferred cells." Dr. Chapuis is one of five researchers recently awarded initial funding in a competition sponsored by the Immunotherapy Integrated Research Center to develop projects that utilize single-cell RNA sequencing (scRNA-seq). An expert in hematopoietic stem cell transplantation, Dr. Chapuis’ laboratory is developing novel ways to modulate the immune system to target cancer. Her research program focuses on identifying factors associated with successful "adoptive" transfer of immune T cells and developing methods that improve the survival, proliferation and anti-tumor activity of infused T cells to better eliminate tumor targets.

During the Nature Webcast, Dr. Chapuis presented her research focusing on T-cell immunotherapy for Merkel Cell Carcinoma (MCC) and highlighted the applications of scRNA-seq to:

  • Elucidate mechanisms of response and tumor escape following endogenous cell therapy
  • Sequence and pair T-cell receptor (TCR) alpha and beta chains to further TCR gene therapy approaches

MCC is an aggressive, rare skin cancer that, in 80% of cases, is caused by Merkel Cell polyomavirus (MCPyV). The MCPyV mutates and integrates into the host genome and persistently expresses T-antigen protein, which is necessary for survival and proliferation. This makes MCPyV oncoproteins an attractive target for T-cell therapy.

Testing different T-cell therapy combinations, Dr. Chapuis and colleagues employed scRNA-seq, using the Chromium™ Single Cell 3’ Solution to look at immune cell populations (as clustered by gene expression) in responders and non-responders, pre- and post-treatment. This approach allowed researchers to elucidate mechanisms of response and escape in patients.

Next, researchers hypothesized that TCRs from antigen-specific cells that appear to mediate clinical responses might have desirable characteristics, such as high-affinity, to confer to other patients. One challenge to this approach was the difficulty of sequencing and pairing the alpha and beta chain sequences from the TCRs that mediate clinical responses. To do this Dr. Chapuis used the Chromium™ Single Cell V(D)J Solution to sequence the full-length alpha and beta chains of the TCRs and thereby identify the precise TCR genotypes associated with clinical efficacy.


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