An adapted anti-CTLA4 therapeutic aimed at mitigating the toxicities of checkpoint inhibition

Research output: Contribution to journalReview article

Abstract

Antibodies that target immune checkpoint molecules, such as CTLA4, provide robust antitumor effects in a subset of patients. Unfortunately, not all patients respond to immune checkpoint inhibition, and some develop life-threatening immune-related adverse events (irAEs). The mechanisms that underlie irAEs from immune checkpoint inhibition are not fully understood, and treatment strategies are currently limited to targeting inflammatory mediators. In this issue of the JCI, Pai et al. report on their development of a modified CTLA4 antibody that shields the inner CTLA4-binding domain until the antibody is within the protease-rich tumor microenvironment. In a lymphopenic murine model reconstituted with naive CD4+ T cells, adapted anti-CTLA4 reduced the occurrence of irAEs and enhanced antitumor effects. This thought-provoking study lays the groundwork for further exploration of this adapted antibody in immunocompetent hosts and introduction of this adaptation to other immune checkpoint molecules. It also suggests that this approach may reduce the incidence of irAEs.

LanguageEnglish (US)
Article numberCI125800
JournalJournal of Clinical Investigation
Volume129
Issue number1
DOIs
StatePublished - Jan 2 2019

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Antibodies
Tumor Microenvironment
Therapeutics
Peptide Hydrolases
T-Lymphocytes
Incidence

ASJC Scopus subject areas

  • Medicine(all)

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An adapted anti-CTLA4 therapeutic aimed at mitigating the toxicities of checkpoint inhibition. / Naidoo, Jarushka; Dykema, Arbor; D'Alessio, Franco.

In: Journal of Clinical Investigation, Vol. 129, No. 1, CI125800, 02.01.2019.

Research output: Contribution to journalReview article

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