Open AccessCombining CD47 blockade with trastuzumab eliminates HER2-positive breast cancer cells and overcomes trastuzumab tolerance
Author(s) -
Rosalynd Upton,
Allison Banuelos,
Dongdong Feng,
Tanuka Biswas,
Kevin S. Kao,
Kelly M. McKenna,
Stephen B. Willingham,
Po Y. Ho,
Benyamin Rosental,
Michal Caspi Tal,
Tal Raveh,
Jens-Peter Volkmer,
Mark D. Pegram,
Irving L. Weissman
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2026849118
Subject(s) - trastuzumab , antibody dependent cell mediated cytotoxicity , breast cancer , cancer research , medicine , monoclonal antibody , cd47 , cancer , antibody , immunology
Significance This study demonstrates the efficacy of combining macrophage-checkpoint inhibition with tumor-specific antibodies for cancer immunotherapy. The combination of anti-CD47 (magrolimab) and anti-HER2 (trastuzumab) antibodies eliminated HER2+ breast cancer cells with increased efficacy due to the enhancement of antibody-dependent cellular phagocytosis by macrophages, even when the cancer cells were tolerant to trastuzumab-induced antibody-dependent cellular cytotoxicity by natural killer cells. We believe these findings present a promising therapeutic approach for treating HER2+ breast cancer patients whose tumors are either sensitive or resistant to trastuzumab treatment, as long as the cells harbor the HER2 trastuzumab-binding epitope. This study supports the notion that combining CD47 blockade with existing macrophage FcR-engaging tumor-specific antibodies may be an effective approach for treating a wide range of cancers.