CD22 is a protein expressed by normal B cells and B-lymphoid malignancies. Its limited tissue expression pattern makes it a safe antigen for targeted therapies, such as T-cell Receptor (TCR)-T cell therapy. CD22-targeting therapies already on the market, mainly antibody-immunotoxin conjugates and chimeric antigen receptors (CAR)-T cells, have limitations such as resistance to treatment and/or side effects. Resistance mechanisms to the current CD22 therapies involve loss or modulation of target antigen on the cell surface. TCRs are expected to overcome these resistance mechanisms as they use distinct target recognition mechanism. TCRs instead recognize epitopes derived from proteins processed intracellularly and presented in the context of Human Leukocyte Antigens (HLA), enabling detection of broad antigens inaccessible to antibodies or CAR-T’s – including neoantigens, cancer germline antigens, and intracellular viral oncoproteins. Investigators at the National Cancer Institute (NCI) developed a TCR recognizing a CD22-derived epitope presented in context of the highly prevalent HLA-A*02:01. The TCR was not cross-reactive against unintended target antigens. T cells expressing the TCR (CD22 TCR-T cells) show anti-tumor activity at clinically-relevant doses without causing systemic cytokine elevation in pre-clinical, in vivo models. The inventors are translating their findings into the clinic. NCI seeks parties interested in licensing and/or collaborations to further develop this technology.
Therapeutic against B-cell malignancies such as non-Hodgkin’s lymphoma, chronic lymphocytic leukemia and acute lymphoblastic leukemia Therapeutic for: