Research Projects

B-cell non-Hodgkin lymphoma (B-NHL) is a prevalent cancer in India, with relapsed or refractory NHL having poor prognosis. CD19 CAR-T therapy is a potentially curative immune cell therapy approved for treating r/r B-NHL, but the emergence of CD19 negative relapse due to mutation necessitates the development of CAR T cells targeting an alternate tumor antigen. CD37, a tetraspanin overexpressed in B-NHL but not in progenitor cells, is also expressed in multiple B lineage cancers and weakly expressed in T cells. Antibodies and peptides targeting CD37 are currently in clinical evaluation. The source of T cells significantly influences the expansion and function of CAR T cells. Peripheral Blood (PB) and Cord Blood (CB) are the two major sources of T cells. PB is preferred due to its availability and abundance of memory T cells, while CB T cells have a immunosuppressive phenotype due to the abundance of regulatory T cells. There is no systematic comparison of therapeutic T cells derived from PB and CB T cells. This in vitro study aims to generate second-generation CAR with CD28 co-stimulatory domain and antigen-binding domain derived from murine anti-humanCD37 hybridoma MB-1. The project will streamline an indigenous workflow to expand T cells engineered to express anti-CD37 CAR in Cord Blood and Peripheral Blood derived T cells from normal donors. The proliferation, phenotype, and anti-tumor effector functions of PB/CB-derived CAR-T cells will be assessed. The hypothesis is that anti-CD37 CAR T cells will target CD19 escape variants positive for CD37 antigen.

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