Paper Spotlight: Therapeutic Efficacy of H2aL2a, H3L3 in Xenograft Models of Human Breast, Lung Cancer

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October 25, 2022

Oncotarget published this research paper in Volume 13, entitled, "Therapeutic efficacy of the humanized JAA-F11 anti-Thomsen-Friedenreich antibody constructs H2aL2a and H3L3 in human breast and lung cancer xenograft models" by researchers from For-Robin, Inc, Williamsville, NY; Department of Biotechnical and Clinical Laboratory Sciences, University at Buffalo, Buffalo, NY; Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, NY; Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY; Department of Medicine, Roswell Park Comprehensive Cancer Center Buffalo, NY. DOI - https://doi.org/10.18632/oncotarget.28282 Correspondence to - Kate Rittenhouse-Olson - krolson@buffalo.edu Abstract The Thomsen-Friedenreich antigen (TF-Ag-α) is found on ~85% of human carcinomas but is cryptic on normal tissue. The humanized highly specific hJAA-F11-H2aL2a and -H3L3 antibodies target TF-Ag-α without binding to TF-Ag-beta (found on surface glycolipids of some normal cells). The relative affinity of H3L3 is 17 times that of H2aL2a, which would seem to favor superior efficacy, however, increased affinity can result in less tumor penetration. To assess the potential therapeutic efficacy of these antibodies, four human cancer- mouse xenograft models were treated with H2aL2a and H3L3. The tumor xenograft models used were human non-small cell lung cancer, H520, and small cell lung cancer, HTB171 in nude mice and human triple negative breast cancer, MDA-MB-231 and HCC1806 in SCID mice. H2aL2a significantly decreased tumor growth in both breast and both lung cancer models. H2aL2a showed statistically equal or better efficacy than H3L3 and has superior production capabilities. These results suggest that H2aL2a may be superior as a naked antibody, as an antibody drug conjugate or as a radiolabeled antibody, however the higher affinity of H3L3 may lead to better efficacy in bi-specific therapies in which the binding is decreased due to the presence of only one TF-Ag-α binding site. Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28282 Press release - https://www.oncotarget.com/news/pr/oncotarget-therapeutic-efficacy-of-humanized-jaa-f-anti-thomsen-friedenreich-antibody-constructs-hala-and-hl-in-human-breast-and-lung-cancer-xenograft-models/ Keywords - breast cancer, lung cancer, xenograft, antigen, antibodies, hJAA-F11, TF-Ag, Thomsen-Friedenreich antigen, tumor immunotherapy, translational oncology About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

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