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Directing p50-IMC to tumors using Fc receptor-bound antibodies (Abs) or surface chimeric antigen receptors (CARs) may increase tumor localization and subsequent phagocytosis of cancer cells by their mature myeloid progeny, potentiating anti-tumor T cell activation. PSMA and EGFR are found on aggressive human prostate cancers, and p50-IMC express receptors that bind the antibody Fc domain. p50-IMC combined with PSMA Ab, EGFR Ab (Cetuximab), or fully humanized PSMA.CAR10.3 manifest increased localization to Myc-CaP murine prostate cancer tumors expressing PSMA or EGFR. Tumor localization is further increased when myelo-depleting 5-fluorouracil precedes p50-IMC administration. Additionally, we find that PSMA Ab, EGFR Ab, or PSMA.CAR10.3 increase in vitro phagocytosis of Myc-CaP cells expressing PSMA or EGFR by p50-IMC-derived macrophages, including in M2-promoting IL-4, which is a component of the immune-suppressive tumor microenvironment. Lack of tolerance of human PSMA or EGFR by immune-competent mice and lack of expression of human PSMA protein in the prostate of AR\n                    <jats:sub>2<\/jats:sub>\n                    -Probasin-hPSMA transgenic mice precluded our ability to determine whether human-specific PSMA or EGFR antibody or PSMA.CAR10.3 increases anti-tumor efficacy of murine p50-IMC. Nevertheless, this study indicates the potential clinical utility of adding a tumor-directing antibody or CAR, including the novel, fully humanized PSMA.CAR10.3, to proinflammatory p50-IMC to optimize the activation of anti-tumor immunity in prostate cancer and other malignancies, and understanding PSMA toxicity in normal but not malignant prostate epithelium may reveal a novel therapeutic opportunity.\n                  <\/jats:p>","DOI":"10.1007\/s00262-024-03939-4","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T11:51:30Z","timestamp":1738669890000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["PSMA antibody, humanized PSMA.CAR10.3, or Cetuximab increases prostate cancer localization of NF-\u03baB p50-deficient immature myeloid cells (p50-IMC) and phagocytosis by their macrophage progeny"],"prefix":"10.1007","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3953-8436","authenticated-orcid":false,"given":"Mohammad A.","family":"Alzubi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7816-1969","authenticated-orcid":false,"given":"Theresa","family":"Barberi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5615-7061","authenticated-orcid":false,"given":"Alan D.","family":"Friedman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,4]]},"reference":[{"key":"3939_CR1","doi-asserted-by":"publisher","first-page":"1126752","DOI":"10.3389\/fonc.2023.1126752","volume":"13","author":"H Liang","year":"2023","unstructured":"Liang H, Liu Y, Guo J, Dou M, Zhang X, Hu L, Chen J (2023) Progression in immunotherapy for advanced prostate cancer. 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