{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:03:38Z","timestamp":1789625018467,"version":"build-2803163510"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We have evaluated PBA-0111, a fully human antibody targeting Glycoprotein A Repetitions Predominant (GARP), designed to induce both antibody-dependent cellular cytotoxicity (ADCC) as well as blockage of Transforming Growth Factor Beta 1 (TGF-\u03b21) activation. Functional assessments included\n                      <jats:italic>in vitro<\/jats:italic>\n                      cytotoxicity assays, inhibition of GARP\/TGF-\u03b21 complex formation and inhibition of TGF-\u03b21 signaling. PBA-0111 was compared with clinically tested anti-GARP antibodies, including DS-1055a- and ABBV-151-like antibodies. Lack of significant binding to human platelets was confirmed by flow cytometry. Anti-tumor efficacy\n                      <jats:italic>in vivo<\/jats:italic>\n                      was assessed in CD34\n                      <jats:sup>+<\/jats:sup>\n                      human stem cell humanized mice xenograft models, including models where GARP was expressed both on tumor cells and regulatory T cells as well as models where GARP was expressed exclusively on regulatory T cells. The potential of PBA-0111 to stimulate immune cell activation inside tumors was further studied in a placebo-controlled Phase 0 clinical study in soft tissue sarcoma patients receiving intra-tumoral injections.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and discussion<\/jats:title>\n                    <jats:p>Our findings demonstrate that PBA-0111 exhibits ADCC activity comparable to DS-1055a-like antibody, which was not observed for ABBV-151-like antibody. PBA-0111 effectively blocks TGF-\u03b21 activation, similar to ABBV-151-like antibody but unlike DS-1055a-like antibody. In contrast to ABBV-151, which blocks TGF-\u03b21 activation within the pre-formed GARP\/TGF-\u03b21 complex, PBA-0111 prevents GARP\/TGF-\u03b21 complex formation itself. Importantly, PBA-0111 did not demonstrate significant binding to human platelets. In humanized mice, whether GARP was expressed on tumor cells or exclusively on Tregs, PBA-0111 treatment induced robust inhibition of tumor growth, whereas DS-1055a-like antibody did not demonstrate any statistically significant anti-tumor efficacy in these models. Tumor growth inhibition by PBA-0111 was accompanied by cytotoxic T cell activation. A similar trend of T cell activation was observed in soft tissue sarcoma patients receiving intra-tumoral injections of PBA-0111 in the Phase 0 clinical trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These results underscore the therapeutic potential of PBA-0111 as a dual-functioning immunotherapy and a promising candidate for the treatment of GARP-positive cancers. This integrated mechanism may amplify anti-tumor immunity, improve synergy with checkpoint inhibitors, and provide more durable reprogramming of the tumor microenvironment than either approach alone.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1921265","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:31:30Z","timestamp":1789623090000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A fully human afucosylated anti-GARP antibody PBA-0111 drives anti-tumor immunity through combined ADCC induction and TGF-\u03b21 pathway blockade"],"prefix":"10.3389","volume":"17","author":[{"given":"Pieter","family":"Spee","sequence":"first","affiliation":[{"name":"MultiQure S.A (Formely Pure Biologics)","place":["Wroc\u0142aw, 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