CD47/SIRPα checkpoint blockade in combination with HER2 antibody for the treatment of HER2-positive breast cancer
Approximately 20% of breast cancers overexpress the human epidermal growth factor receptor type 2 (HER2), which is recognized as an oncogenic driver of an aggressive cancer phenotype with a poor prognosis. The clinical benefit associated with trastuzumab, a humanized monoclonal antibody specific for patients with HER2-positive breast cancer remains heterologous and metastatic HER2-positive breast cancer remains incurable. Accordingly, there is a great need to dissect the precise mechanisms of the antitumor mechanisms of action of trastuzumab in order to improve outcomes in patients with HER2-positive breast cancer.
Researchers at Duke have identified a novel strategy to overcome resistant to anti-HER2 therapy utilizing macrophage checkpoint blockade. Blocking the CD47–SIRPα checkpoint augmented trastuzumab therapeutic outcomes through enhanced antibody-dependent cellular phagocytosis of tumor cells. Human HER2-positive breast cancer xenografts treated with trastuzamab together with CD47 blocking antibody underwent complete tumor regression. Furthermore, CD47 blockade increased therapeutic efficacy of anti-HER2 monoclonal antibody and improved antitumor responses and prolonged survival in orthotopic murine model of HER2-positive breast cancer.
CD47-SIRPα checkpoint blockade in combination with trastuzumab can be used to treat
other HER2-positive cancers, including gastric cancer.
- CD47 may be functioning in trastuzumab-treated breast cancer patients to mediate therapeutic resistance
- CD47 blockade can improve outcomes for HER2-positive breast cancer