Preclinical Characterization of a Novel Monoclonal Antibody NEO-201 for the Treatment of Human Carcinomas

Frontiers in Immunology

Yongzhi Cui¹  Philip M. Arlen¹  Sharon A. Mavroukakis¹  Olga Saric¹  Kwong Y. Tsang¹  Massimo Fantini¹  Justin M. David¹  Alexander Dubeykovskiy¹  Andrew Bristol²  Christina M. Annunziata³ 

[1] Precision Biologics, Inc., Rockville, MD, United States;Synthetic Biologics, Inc., Rockville, MD, United States;Women’s Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States;

关键词: monoclonal antibody;    tumor-associated antigen;    antibody-dependent cellular cytotoxicity;    complement-dependent cytotoxicity;    natural killer cell;   

DOI  :  10.3389/fimmu.2017.01899

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown