Unmet Need: Prostate cancer is one of the most commonly diagnosed cancers in the male population; roughly one out of ten men will be diagnosed at some point in their lives. Despite extending survival, androgen depravation therapy invariably leads to the development of lethal castration resistant prostate cancer. Similarly, pancreatic ductal carcinoma and glioblastoma brain tumors are also almost universally fatal. These tumors recruit and transforms beneficial immune macrophages into pro-tumor agents that encourage cancer cell proliferation and metastasis in part due to suppression of the patient’s immune response. Reverting pro-tumor macrophages into immune-stimulating macrophages is an attractive approach to cancer immunotherapy, for patients with prostate cancer or other malignancies.
Technology Overview: Johns Hopkins researchers developed a methodology to convert patient’s immune cells from pro-tumor macrophages to immune-stimulatory cells using genetic manipulation. Mice lacking p50, a subunit of NF-κB, display slower tumor growth after being challenged with a number of different cancers. The investigators isolated stem cells from the bone marrow of p50 deficient mice. These cells were expanded and then differentiated into immature myeloid cells with immune-stimulatory macrophage and dendritic cell potential, in culture, and injected into mice harboring various cancers. Mice receiving the p50 deficient myeloid cells demonstrated decreased prostate cancer, pancreatic ductal carcinoma, neuroblastoma, and glioblastoma growth compared to those receiving wild-type myeloid cells cultured in the same conditions. The researchers have developed CRISPR/Cas9 approaches to knockout p50 in human bone marrow stem cells thus enabling this technology for clinical application in multiple cancer indications.
Stage of Development: Data from animal models and human p50-deficient myeloid cells is available.
Publications
Suresh et al. NF-κB p50-deficient immature myeloid cell (p50-IMC) adoptive transfer slows the growth of murine prostate and pancreatic ductal carcinoma. J. Immunother. Cancer 2020;8(1).
Cui et al. Adoptive transfer of immature myeloid cells lacking NF-κB p50 (p50-IMC) impedes the growth of MHC-matched high-risk neuroblastoma. Mol. Oncol. 2021;15.
Beck PJ et al. Adoptive transfer of NF-κB p50 knockout immature myeloid cells shows a trend towards slower glioblastoma tumor growth in an orthotopic mouse model. Cancer Res. 2022; 83(Suppl. 7; AACR meeting abstract).
Barberi T, Friedman AD. Human macrophages lacking NF-κB p50 display increased proinflammatory cytokine expression. J. Immunoth. Cancer 2023; 11(Suppl. 1; SITC meeting abstract).
