Abstract
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.
Highlights
Cancer represents one of the most frequent causes of mortality worldwide, with an estimated 20 million new cases expected annually as early as 2025 [1]
Humanization was performed in silico by replacing mouse sequences outside the complementarity-determining regions (CDRs) of the Fab region of both heavy and light chain proteins with human Fab sequences, and retaining the three mouse CDR sequences from each chain
We have previously reported the preclinical antitumor activity [17] as well as clinical safety and efficacy [18, 19] for a monoclonal antibodies (mAbs) generated against the Hollinshead allogeneic colorectal cancer vaccine platform, termed ensituximab (NPC-1C/NEO-102)
Summary
Cancer represents one of the most frequent causes of mortality worldwide, with an estimated 20 million new cases expected annually as early as 2025 [1]. The immunoediting process occurs in three phases; elimination, equilibrium, and escape. During the elimination and equilibrium phases, respectively, immune rejection of cancer cells either predominates or balances with cancer cell proliferation to control malignant growth. Cancer cells that escape immune recognition are able to more freely proliferate and grow into clinically apparent disease [4]. The aim of cancer immunotherapy is to keep cancer cells in the elimination and/or equilibrium phase by generating and/or amplifying antitumor immune responses to counteract tumor growth, delay tumor recurrence, and prolong survival [5,6,7,8]. Common approaches include treating patients with checkpoint inhibitory antibodies, antitumor vaccines, and chimeric antigen receptor-T cells, all of which leverage adaptive immunity by T cells. Innate immunity can generate and potentiate antitumor responses, and tumor-targeting monoclonal antibodies (mAbs) can be used to stimulate innate antitumor immunity [9]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call