In this case-report published in Nature Medicine, Zacharakis et al (Nat Med, 2018) increased efficacy and reduced the risk of side effects of a tumor-infiltrating lymphocyte (TIL)-product by teasing out only the neoantigen reactive clones rather than expanding bulk TILs. The authors first sequenced the breast cancer lesion and found somatic mutations, and subsequently screened the TILs for reactivity to the found neoantigens using ELISpot Plus: Human IFN-γ. By rapidly expanding only the reactive clones, the authors were able to infuse large numbers of tumor-specific T cells after pre-conditioning therapy.
After just 6 weeks, the tumor burden had decreased to 50%, and 22 months after cell transfer there were no more lesions to be found. Interestingly, eight of the 11 neoantigen-reactive T cell clones persisted in the patient’s blood at least 17 months after infusion.
This particular paper shows a hyper-personalized approach with cell therapy, but the lessons learned from it may pave the way for a slightly less personalized future version of the approach where instead of using TILs, one could engineer the found mutation-specific TCRs into autologous T cells from peripheral blood.
Learn more about why ELISpot and FluoroSpot are key immunoassays to use in cell and gene therapy evaluation and get inspired!
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