Accession Number:

ADA612829

Title:

Evaluation of the Immunologic Impact of RAF Inhibitors to Guide Optimal Combination of RAF Inhibitors and Immunotherapy for the Treatment of Advanced Melanoma

Descriptive Note:

Annual rept. 15 Sep 2012-14 Sep 2013

Corporate Author:

MEMORIAL SLOAN-KETTERING CANCER CENTER NEW YORK

Personal Author(s):

Report Date:

2013-10-01

Pagination or Media Count:

14.0

Abstract:

,During this first year of funding, we have made the following important observations. 1 T cells activated in vitro in the presence of BRAF inhibitors demonstrate a pattern of paradoxical activation characterized by upregulation of activation markers CD69, PD-1, ICOS and hyperactivation of the ERK signaling pathway. 2 T cells activated in vivo in the presence of BRAF inhibitors also demonstrate a pattern of paradoxical activation demonstrated by increased T cell expansion in vivo and hyperactivation of the ERK signaling pathway. 3 T cells activated in vitro in the presence of MEK inhibitors demonstrate inhibited upregulation of activation markers CD69, PD-1, ICOS and inhibition of the ERK signaling pathway. 4 T cells activated in vivo in the presence of MEK inhibitors also demonstrate a pattern of diminished activation demonstrated by lower T cell expansion in vivo and inhibition of the ERK signaling pathway. These first two observations have been reported in a manuscript that has been accepted for publication in the Journal Cancer Immunology Research. In addition, we have completed the following milestones that will form the foundation for future work 1 regulatory approval for mouse studies, 2 regulatory approval for human correlative studies and 3 expansion of the BRAFPTEN mouse colony.

Subject Categories:

  • Medicine and Medical Research
  • Pharmacology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE