The Society for Immunotherapy of Cancer (SITC) is pleased to present highlights
from the first day of the 32nd Annual Meeting in National Harbor, Md. (Scroll to the bottom of this blog post to view the Glossary)
Co-administration of novel anti-sMIC antibody increases anti-CTLA-4 therapeutic response in TRAMP/MIC mice (O22)
Jennifer Wu, PhD (Northwestern
University, Chicago, IL) presented recently-published data investigating the
efficacy of a novel antibody targeting the highly immunosuppressive human
activation immune receptor natural killer group 2D (NKG2D) ligand, sMIC, with
the goal of increasing anti-CTLA-4 therapeutic response. Using a TRAMP
(transgenic adenocarcinoma of the mouse prostate)/MIC mouse model, Wu’s group
found that mice with increased circulation of tumor-derived sMIC receiving
anti-CTLA-4 had ~25% decrease in survival over 8 weeks compared to mice
receiving placebo (p < 0.05), as well as an increased risk of immune-related
colitis. TRAMP/MIC mice receiving anti-CTLA-4 in combination with anti-sMIC had
reduced prostate tumor burden (~0.25g vs ~6g, respectively; p < 0.001),
increased DC activation, enhanced TCR/CD3 signaling, and increased T cell
clonality in tumor infiltrates compared to mice receiving anti-CTLA-4 alone (P
< 0.05). CR was observed in 4/5 combination-treated mice for at least 120
days post-therapy, with no cases of immune-related colitis. These pre-clinical
anti-sMIC/anti-CTLA-4 data align with clinical observations in patients with
mCRPC, melanoma and multiple myeloma who have demonstrated improved responses
to anti-CTLA-4 therapy if they develop sMIC autoantibodies during the course of
treatment. These results suggest that sMIC may act as a predictive biomarker
for anti-CTLA-4 response. Furthermore, including anti-sMIC antibodies in
CTLA-4-targeted therapies may reduce irAES and increase treatment efficacy.
