Combinatorial therapy
The meeting featured many examples of combining CAR T cell therapy with other substances to improve its efficacy and safety:
- Carl June (USA) discussed how adding Ibrutinib to the CAR T therapy appears to result in increased safety and substantially better efficacy in CLL patients.
- Michael Hudecek (Germany) mentioned that scientists are exploring FMS-like tyrosine kinase 3 (FLT3) as a target in AML. The results are encouraging, with potent anti-leukemia activity of FLT3 CAR T cells in vitro and in vivo. Combining the CAR T cell therapy with an FLT3 inhibitor appears to result in enhanced recognition of tumor cells by the CAR T cells. This is because the tumor cells upregulate the expression of FLT3 upon encountering the FLT3 inhibitor. The scientists are currently exploring the optimal combination of various types of FLT3 inhibitors.
- Stanley Riddell (USA) presented a trial with BCMA CAR T cells in very advanced MM patients. The researchers showed that tumor recurrence was associated with loss of BCMA expression. Surface expression of BCMA is regulated by gamma secretase. Therefore, Riddell’s laboratory is testing a small molecule inhibitor of this enzyme (GSI) to prevent shedding of BCMA. Indeed, GSI upregulates BCMA on patient myeloma cells in vitro and enhances CAR T cell recognition. Based on these data, they have initiated a clinical trial where they treat patients with GSI before and after CAR T cell infusion.
- In a ‘best abstracts’ session, Beatrice Greco (Italy) discussed how combining de-glycosylating agents with CAR T Cells may be used for targeting solid tumors and reducing toxicity.
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