Preclinical Characterization of a Novel Monoclonal Antibody NEO-201 for the Treatment of Human Carcinomas
| Autor: | Massimo Fantini, Philip M. Arlen, Christina M. Annunziata, Kwong Y. Tsang, Olga Saric, Andrew Bristol, Sharon Mavroukakis, Alexander Dubeykovskiy, Justin M. David, Yongzhi Cui |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy medicine.drug_class tumor-associated antigen Immunology Monoclonal antibody Peripheral blood mononuclear cell Natural killer cell 03 medical and health sciences 0302 clinical medicine Antigen In vivo Immunology and Allergy Medicine complement-dependent cytotoxicity Original Research Antibody-dependent cell-mediated cytotoxicity biology business.industry natural killer cell Complement-dependent cytotoxicity 030104 developmental biology medicine.anatomical_structure monoclonal antibody 030220 oncology & carcinogenesis biology.protein Cancer research Antibody business lcsh:RC581-607 antibody-dependent cellular cytotoxicity |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 8 (2018) |
| ISSN: | 1664-3224 |
| Popis: | NEO-201 is a novel humanized IgG1 monoclonal antibody that was derived from an immunogenic preparation of tumor-associated antigens from pooled allogeneic colon tumor tissue extracts. It was found to react against a variety of cultured human carcinoma cell lines and was highly reactive against the majority of tumor tissues from many different carcinomas, including colon, pancreatic, stomach, lung, and breast cancers. NEO-201 also exhibited tumor specificity, as the majority of normal tissues were not recognized by this antibody. Functional assays revealed that treatment with NEO-201 is capable of mediating both antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against tumor cells. Furthermore, the growth of human pancreatic xenograft tumors in vivo was largely attenuated by treatment with NEO-201 both alone and in combination with human peripheral blood mononuclear cells as an effector cell source for ADCC. In vivo biodistribution studies in human tumor xenograft-bearing mice revealed that NEO-201 preferentially accumulates in the tumor but not organ tissue. Finally, a single-dose toxicity study in non-human primates demonstrated safety and tolerability of NEO-201, as a transient decrease in circulating neutrophils was the only related adverse effect observed. These findings indicate that NEO-201 warrants clinical testing as both a novel diagnostic and therapeutic agent for the treatment of a broad variety of carcinomas. |
| Databáze: | OpenAIRE |
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