Oncotarget

Research Papers:

Therapeutic efficacy of the humanized JAA-F11 anti-Thomsen-Friedenreich antibody constructs H2aL2a and H3L3 in human breast and lung cancer xenograft models

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 _

PDF  |  Full Text  |  Supplementary Files  |  How to cite  |  Press Release  |  Order a Reprint

Oncotarget. 2022; 13:1155-1164. https://doi.org/10.18632/oncotarget.28282

Metrics: PDF 209 views  |   Full Text 959 views  |   ?  


Abstract

Diala Ghazal1,2, Fatma Zalzala1, John C. Fisk1, Swetha Tati1, Loukia G. Karacosta1, Susan Morey1,2, James R. Olson1,3, Sally Quataert1,4, Grace K. Dy5 and Kate Rittenhouse-Olson1,2

1 For-Robin, Inc, Williamsville, NY 14221, USA

2 Department of Biotechnical and Clinical Laboratory Sciences, University at Buffalo, Buffalo, NY 14214, USA

3 Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, NY 14203, USA

4 Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY 14642, USA

5 Department of Medicine, Roswell Park Comprehensive Cancer Center Buffalo, NY 14203, USA

Correspondence to:

Kate Rittenhouse-Olson, email: krolson@buffalo.edu

Keywords: hJAA-F11; TF-Ag; Thomsen-Friedenreich antigen; tumor immunotherapy; translational oncology

Received: August 10, 2022     Accepted: October 03, 2022     Published: October 19, 2022

Copyright: © 2022 Ghazal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 28282