Unmet Need: Prostate cancer remains one of the leading causes of cancer-related death among men. Clinical translation of PSMA-CAR-T cell therapies under investigation is hindered by questions as to their tumor infiltration, efficacy, and durability. Immature myeloid cells deficient in the p50-subunit of NF-κB (p50-IMCs) enhance T cell activation. As such, this invention discloses novel compositions comprising PSMA-targeted p50-IMCs as a novel immunotherapy capable of effectively inducing proinflammatory T cell activation at the tumor site.
Value Proposition:
· PSMA-targeted p50-IMC cell therapy for prostate cancer
· Engineered p50-IMCs expressing a fully humanized Chimeric Antigen Receptor (CAR) for selective PSMA targeting
· Effectively induces a proinflammatory phenotype and enhanced T cell activation resulting in potent anti-tumor response
· Platform adaptable to other antigens and broad use in various cancer types
Technology Overview: Johns Hopkins researchers developed an engineered PSMA-targeting p50-IMC CAR as a novel cell therapy for prostate cancer. Prior work demonstrated the ability of p50-IMC to effectively reach the tumor site and activate T cell immunity to slow tumor growth. Here, p50-IMC was engineered to express a fully humanized CAR that recognizes PSMA, therefore increasing localization to prostate cancer tumors and phagocytosis of PSMA-expressing prostate cancer cells. This new approach presents a versatile platform to engineer proinflammatory myeloid cell immunotherapies targeting antigens of choice for broad application in prostate cancer or other types of malignancies.
Stage of Development: Data from animal models is available. A fully humanized PSMA CAR has been validated for inducing myeloid cell tumor localization and PSMA-dependent phagocytosis.
Publications
Alzubi MA et al. Impact of PSMA antibody or chimeric antigen receptor on phagocytosis and tumor localization by wild-type and NF-κB p50-deficient macrophages. J. Immunoth. Cancer 2023; 11(Suppl. 1; SITC meeting abstract).
