Toxicological and pharmacological assessment of AGEN1884, a novel human IgG1 anti-CTLA-4 antibody Journal Article


Authors: Gombos, R. B.; Gonzalez, A.; Manrique, M.; Chand, D.; Savitsky, D.; Morin, B.; Breous-Nystrom, E.; Dupont, C.; Ward, R. A.; Mundt, C.; Duckless, B.; Tang, H.; Findeis, M. A.; Schuster, A.; Waight, J. D.; Underwood, D.; Clarke, C.; Ritter, G.; Merghoub, T.; Schaer, D.; Wolchok, J. D.; van Dijk, M.; Buell, J. S.; Cuillerot, J. M.; Stein, R.; Drouin, E. E.; Wilson, N. S.
Article Title: Toxicological and pharmacological assessment of AGEN1884, a novel human IgG1 anti-CTLA-4 antibody
Abstract: CTLA-4 and CD28 exemplify a co-inhibitory and co-stimulatory signaling axis that dynamically sculpts the interaction of antigen-specific T cells with antigen-presenting cells. Anti-CTLA-4 antibodies enhance tumor-specific immunity through a variety of mechanisms including: blockade of CD80 or CD86 binding to CTLA-4, repressing regulatory T cell function and selective elimination of intratumoral regulatory T cells via an Fcγ receptor-dependent mechanism. AGEN1884 is a novel IgG1 antibody targeting CTLA-4. It potently enhanced antigen-specific T cell responsiveness that could be potentiated in combination with other immunomodulatory antibodies. AGEN1884 was well-tolerated in non-human primates and enhanced vaccine-mediated antigen-specific immunity. AGEN1884 combined effectively with PD-1 blockade to elicit a T cell proliferative response in the periphery. Interestingly, an IgG2 variant of AGEN1884 revealed distinct functional differences that May have implications for optimal dosing regimens in patients. Taken together, the pharmacological properties of AGEN1884 support its clinical investigation as a single therapeutic and combination agent. © 2018 Gombos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Journal Title: PLoS ONE
Volume: 13
Issue: 4
ISSN: 1932-6203
Publisher: Public Library of Science  
Date Published: 2018-04-04
Start Page: e0191926
Language: English
DOI: 10.1371/journal.pone.0191926
PROVIDER: scopus
PMCID: PMC5884502
PUBMED: 29617360
DOI/URL:
Notes: Article -- Export Date: 1 May 2018 -- Source: Scopus
Altmetric
Citation Impact
MSK Authors
  1. Jedd D Wolchok
    823 Wolchok
  2. Taha Merghoub
    297 Merghoub
  3. David A Schaer
    25 Schaer