{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:01:51Z","timestamp":1789664511664,"version":"4.0.1"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"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>Introduction<\/jats:title>\n                    <jats:p>B-cell malignancies, including chronic lymphocytic leukemia (CLL), pose a significant clinical challenge due to high relapse rates and dose-limiting toxicities seen with current therapies, particularly in elderly patients. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an attractive therapeutic target due to its high expression on malignant B-cells and minimal presence in normal adult tissues, allowing the development of more potent and safer drugs for cancer treatment. PBA-0405 (called 2.0405.aF in this manuscript) is a novel, fully human afucosylated anti-ROR1 monoclonal antibody, specifically engineered for optimal induction of antibody-dependent cellular cytotoxicity (ADCC) to improve treatment of cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We evaluated 22.0405.aF for ADCC activity and tumor-cell killing in comparison with clinically tested anti-ROR1 antibodies, including zilovertamab and R12. Functional assessment included\n                      <jats:italic>in vitro<\/jats:italic>\n                      cytotoxicity assays,\n                      <jats:italic>ex vivo<\/jats:italic>\n                      killing of patient-derived malignant B cells, and in vivo testing in humanized mice and murine xenograft models of hematologic and solid tumors. Safety was assessed through monitoring of healthy B-cell viability and toxicity\n                      <jats:italic>in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and discussion<\/jats:title>\n                    <jats:p>\n                      Our findings demonstrate that 22.0405.aF exhibits far superior ADCC activity compared to anti-ROR1 antibodies, e.g. zilovertamab and R12, tested in clinical trials  thus far. 22.0405.aF displayed potent tumor cell killing, both\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      , and induced more potent killing of patient-derived malignant B-cells\n                      <jats:italic>ex vivo<\/jats:italic>\n                      compared to rituximab, without affecting healthy B-cells. Furthermore, in humanized mice, in murine xenograft models of both hematological and solid tumors, 22.0405.aF treatment induced robust inhibition of tumor growth without detectable toxicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These results underscore the therapeutic potential of 22.0405.aF as a promising immunotherapy for treatment of ROR1-positive B-cell malignancies. Notably, 22.0405.aF has recently completed Phase 0 clinical trials in patients with head and neck carcinomas and soft tissue sarcomas, paving the way for further clinical development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1711509","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T06:44:29Z","timestamp":1765953869000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["A novel fully human anti-ROR1 antibody PBA-0405 optimized for ADCC, induces potent anti-tumor activity against both solid and hematological 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