Anti-mCTLA-4 treatment results in early and late immune response effects in a murine model of colorectal carcinoma

Date: 2019

Authors: David Draper, Alden Wong, Stacey Roys, Scott Wise, and Maryland Rosenfeld Franklin

AACR Annual Meeting

POSTER | Anti-mCTLA-4 Treatment Results in Early and Late Immune Response Effects in Murine Model of Colorectal Carcinoma (PDF)

Introduction and Background:

  • During pre-clinical research, analysis of the tumor immune response at a single post-treatment timepoint is often standard when therapeutic mechanism of action is investigated.
  • The use of a single sampling point for analysis can limit research on new immune modulation therapies as it provides only a partial view into the dynamic nature of the developing immune response in the tumor.
  • In this study we examined the kinetics of tumor-directed immune infiltration and activation on day 11 and day 17 post-implantation using the CT26 model for colorectal carcinoma.
  • The CT26 model is moderately responsive to checkpoint inhibition. To examine early and late effects that checkpoint inhibition has on the immune response, tumor-bearing mice were treated with anti-mCTLA-4. Tumor analysis corresponded to day 4 and day 10 post-treatment.
  • Endpoints analyzed consisted of:
    • 11 distinct tumor-infiltrating subsets
    • CD8+ T cell activation marker expression
    • T cell cytokine analysis
    • Effector/Memory T cell phenotype
  • We hypothesized that multiple sampling points would uncover unique immune subset specific profiles of infiltration and activation in the CT26 tumor.

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