Targeting cytotoxic T-lymphocyte antigen 4 in immunotherapies for melanoma and other cancers

Immunotherapy
David PageJedd D Wolchok

Abstract

The immune system can simultaneously protect against tumor growth and sculpt resistant tumor strains. By a variety of mechanisms, anti-cytotoxic T-lymphocyte antigen (CTLA)-4 therapy may shift such opposing forces towards tumor elimination. In recent clinical trials, anti-CTLA-4 therapy induces durable responses that correlate with markers of immune activity, such as antigen-specific CD4(+) or CD8(+) cytokine release, antitumor antibody formation or cellular phenotype differentiation. However, some patients exhibit atypical responses to anti-CTLA-4 therapy, demonstrating transient/delayed responses or heterogeneity by lesion site. Such atypical responses may offer insight into the mechanism of anti-CTLA-4 therapy. The immunogram - a newly described graphical synthesis of treatment data and immune correlates in individual patients - may help us to confirm, reject or formulate new hypotheses regarding the mechanism of anti-CTLA-4 activity.

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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
flow cytometry
hormone replacement
ISA
biopsies

Clinical Trials Mentioned

NCT00636168
NCT00836407
NCT00871481
NCT00050102
NCT00527735
NCT00170157

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