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.
- Established market need and regulatory path – following Accelerated Approval of Inotuzumab ozogamicin in 2017.
- T cells expressing the CD22 TCR (CD22 TCR-T cells) mediate dose-dependent anti-tumor activity in leukemia and lymphoma models in vivo.
- CD22 TCR-T cells, but not T cells expressing a comparable CAR (CD22 CAR-T cells), clear leukemia at clinically-relevant doses and without causing systemic cytokine elevation.
- CD22 TCR-T cells are not cross-reactive against other human proteins.
Therapeutic against B-cell malignancies such as non-Hodgkin’s lymphoma, chronic lymphocytic leukemia and acute lymphoblastic leukemia
- CD22-expressing malignancies, even if the CD22 antigen escapes the surface of the tumor cells and resides within intracellular compartments or is only partially expressed
- CD22-expressing malignancies, even if the diseases are resistant to existing anti CD22 antibodies through resistance to antibody-specific cytotoxicity mechanisms (such as antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity).