{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:42:21Z","timestamp":1791513741678,"version":"4.3.4"},"reference-count":46,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T00:00:00Z","timestamp":1621900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Folate receptor beta (FR\u03b2) is a folate binding receptor expressed on myeloid lineage hematopoietic cells. FR\u03b2 is commonly expressed at high levels on malignant blasts in patients with acute myeloid leukemia (AML), as well as on M2 polarized tumor-associated macrophages (TAMs) in the tumor microenvironment of many solid tumors. Therefore, FR\u03b2 is a potential target for both direct and indirect cancer therapy. We demonstrate that FR\u03b2 is expressed in both AML cell lines and patient-derived AML samples and that a high-affinity monoclonal antibody against FR\u03b2 (m909) has the ability to cause dose- and expression-dependent ADCC against these cells in vitro. Importantly, we find that administration of m909 has a significant impact on tumor growth in a humanized mouse model of AML. Surprisingly, m909 functions in vivo with and without the infusion of human NK cells as mediators of ADCC, suggesting potential involvement of mouse macrophages as effector cells. We also found that TAMs from primary ovarian ascites samples expressed appreciable levels of FR\u03b2 and that m909 has the ability to cause ADCC in these samples. These results indicate that the targeting of FR\u03b2 using m909 has the potential to limit the outgrowth of AML in vitro and in vivo. Additionally, m909 causes cytotoxicity to TAMs in the tumor microenvironment of ovarian cancer warranting further investigation of m909 and its derivatives as therapeutic agents in patients with FR\u03b2-expressing cancers.<\/jats:p>","DOI":"10.3390\/ijms22115572","type":"journal-article","created":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T13:14:21Z","timestamp":1621948461000},"page":"5572","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Folate Receptor Beta as a Direct and Indirect Target for Antibody-Based Cancer Immunotherapy"],"prefix":"10.3390","volume":"22","author":[{"given":"Allison G.","family":"Roy","sequence":"first","affiliation":[{"name":"Ovarian Cancer Research Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Center for Cellular Immunotherapies, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Michael","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Zimmer Cancer Center, New Hanover Regional Medical Center, Wilmington, NC 28401, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prannda","family":"Sharma","sequence":"additional","affiliation":[{"name":"Ovarian Cancer Research Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Center for Cellular Immunotherapies, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Rodriguez-Garcia","sequence":"additional","affiliation":[{"name":"Ovarian Cancer Research Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Center for Cellular Immunotherapies, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4603-3508","authenticated-orcid":false,"given":"Mathilde A.","family":"Poussin","sequence":"additional","affiliation":[{"name":"Ovarian Cancer Research Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Center for Cellular Immunotherapies, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Nickerson-Nutter","sequence":"additional","affiliation":[{"name":"Three Lakes Foundation, Northbrook, IL 60062, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5966-8908","authenticated-orcid":false,"suffix":"Jr.","given":"Daniel J.","family":"Powell","sequence":"additional","affiliation":[{"name":"Ovarian Cancer Research Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Center for Cellular Immunotherapies, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.7150\/jca.24577","article-title":"Current status and future directions of cancer immunotherapy","volume":"9","author":"Zhang","year":"2018","journal-title":"J. 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