Selecting Adjuvants to Support Adoptive T Cell Therapy
Dr. Martin McIntosh, Fred Hutchinson Cancer Research Center
A growing number of cancer patients will be offered some type of adoptive T cell therapy, especially after conventional therapies fail3. Some patients have experienced dramatic improvements following T cell therapy, but many patients, even those whose tumors possess the target antigen, have not. Response rates could be improved by modulating the tumor microenvironment toward a state that is more supportive of immune function, and a number of existing tools can do this to some degree4,5; including cytokines, interleukins, interferons, checkpoint blockade (PD-1/PD-L1, BTLA-4, etc.), and others. Effective modulation strategies may require developing a molecular toolkit (assays and algorithms) that can accurately assess factors that are actionable and is practical for use in a clinical setting.
We plan to use the PanCancer Immune Profiling Panel to identify which actionable factors can be measured adequately using nucleic acid-based assays, with the goal to develop a parsimonious companion diagnostic for T cell therapies. This may be challenging for many reasons, including that solid tumors vary in ways that can confound appropriate interpretation, e.g. variations in both the cellular composition and in the expression level of specific cells in it. To start, we would profile tissues whose cellular composition and immune-environment has also been measured by gold-standard assays such as IHC, and also by clinically impractical flow cytometry, including tissues from patients who are enrolled in T cell therapy trials.
3 Pedrazzoli P, Comoli P, Montagna D, Demirer T, Bregni M. (2012) Is adoptive T-cell therapy for solid tumors coming of age? Bone Marrow Transplant 47:1013–1019.
4 Tey SK, Bollard CM, Heslop HE (2006) Adoptive T-cell transfer in cancer immunotherapy. Immunol Cell Biol 84:281–289.