Journal
SCIENCE TRANSLATIONAL MEDICINE
Volume 7, Issue 315, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aac4925
Keywords
-
Categories
Funding
- Wilhelm Sander-Stiftung fur Krebsforschung
- Swiss Group for Clinical Cancer Research (SAKK)/Amgen research grant
- Swiss National Science Foundation
- Krebsliga beider Basel
- Sassella-Stiftung
- Huggenberger-Bischoff Stiftung zur Krebsforschung
- Freiwillige Akademische Gesellschaft Basel
- Whitaker International Scholars Program
- Roche
Ask authors/readers for more resources
Targeted drug delivery with antibody-drug conjugates such as the HER2-directed ado-trastuzumab emtansine (T-DM1) has emerged as a powerful strategy for cancer therapy. We show that T-DM1 is particularly effective in eliciting antitumor immunity in patients with early breast cancer (WSG-ADAPT trial) and in a HER2-expressing orthotopic tumormodel. In the latter, despite primary resistance to immunotherapy, combined treatment with T-DM1 and anti-CTLA-4/PD-1 (cytotoxic T lymphocyte-associated protein-4/programmed cell death protein-1) was curative because it triggered innate and adaptive immunity. Tumor rejection was accompanied bymassive T cell infiltration, T(H)1 (T helper 1) cell polarization, and, notably, a substantial increase in regulatory T cells. Depletion of regulatory T cells resulted in inflammation and tissue damage, implying their essential role in protecting the host during therapy. This study provides insights into the mechanisms of T-DM1' s therapeutic activity and a rationale for potential therapeutic combination strategies with immunotherapy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available