A new research paper was published in Oncotarget's Volume 13 on October 19, 2022, entitled, “Therapeutic efficacy of the humanized JAA-F11 anti-Thomsen-Friedenreich antibody constructs H2aL2a and H3L3 in human breast and lung cancer xenograft models.”
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.”
In a new study, researchers Diala Ghazal, Fatma Zalzala, John C. Fisk, Swetha Tati, Loukia G. Karacosta, Susan Morey, James R. Olson, Sally Quataert, Grace K. Dy, and Kate Rittenhouse-Olson from For-Robin, Inc, University at Buffalo, University of Rochester, and Roswell Park Comprehensive Cancer Center Buffalo aimed to assess the potential therapeutic efficacy of these antibodies by treating four human cancer- mouse xenograft models 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.
“In conclusion, both H2aL2a and H3L3 humanized antibodies to TF-Ag-α show efficacy in in vivo xenograft models of human tumors in SCID and nude mice and thus hold promise as therapeutics for breast and lung cancer. H2aL2a significantly decreased tumor growth rate in both breast cancer and both lung cancer models tested. H2aL2a is equal to or better than H3L3 in four of the four models and H2aL2a cell lines have far superior antibody production capabilities under the conditions tested.”
DOI: https://doi.org/10.18632/oncotarget.28282
Correspondence to: Kate Rittenhouse-Olson - krolson@buffalo.edu
Keywords: hJAA-F11, TF-Ag, Thomsen-Friedenreich antigen, tumor immunotherapy, translational oncology
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