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Review
. 2020 Mar 12:6:10.
doi: 10.1038/s41523-020-0153-3. eCollection 2020.

Clinical development of immunotherapies for HER2+ breast cancer: a review of HER2-directed monoclonal antibodies and beyond

Ricardo L B Costa  1 , Brian J Czerniecki  1
Affiliations
Review

Clinical development of immunotherapies for HER2+ breast cancer: a review of HER2-directed monoclonal antibodies and beyond

Ricardo L B Costa et al. NPJ Breast Cancer. .

Abstract

Human epidermal growth factor receptor 2-positive (HER2+) breast cancer accounts for ~25% of breast cancer cases. Monoclonal antibodies (mAbs) against HER2 have led to unparalleled clinical benefit for a subset of patients with HER2+ breast cancer. In this narrative review, we summarize advances in the understanding of immune system interactions, examine clinical developments, and suggest rationales for future investigation of immunotherapies for HER2+ breast cancer. Complex interactions have been found between different branches of the immune system, HER2+ breast cancer, and targeted treatments (approved and under investigation). A new wave of immunotherapies, such as novel HER2-directed mAbs, antibody drug conjugates, vaccines, and adoptive T-cell therapies, are being studied in a broad population of patients with HER2-expressing tumors. The development of immunotherapies for HER2+ breast cancer represents an evolving field that should take into account interactions between different components of the immune system.

Keywords: Breast cancer; Metastasis.

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Conflict of interest statement

Competing interestsR.L.B.C. received honorarium from Bristol Meyers Squib and Pfizer; he has also received a research grant from Bristol Meyers Squib. B.J.C. has intellectual property potential on the DC1 vaccine.

Figures

Fig. 1
Fig. 1. Depiction of immune response to breast cancer expressing HER2.
HER2 antigen is processed by APC, leading to activation of cellular cytotoxic adaptive response (i.e., Th1 response mediated by CD4+ helper lymphocytes). CD8+ CTL can recognize the HER2 antigen through MHC I, leading to cytotoxic activity; breast cancer PD-L1 inhibitory activity and NK activation and function are also shown. The arrow depicts stimulatory effect.
Fig. 2
Fig. 2. Preparation of HER2-pulsed dendritic cells vaccines.
Preparation of the vaccine is a multi-step process starting with leukapheresis and countercurrent centrifugal elutriation to obtain the relevant monocyte pool. This monocyte pool is then treated with GM-CSF and IL-4, then pulsed with HER peptides and matured with IFN-γ and LPS for conversion into type 1 dendritic cells.
Fig. 3
Fig. 3. Possible areas of HER2 immunotherapy clinical development.
Th1 response against HER2 breast cancer cells supported by CD8+, CD4+, NK lymphocytes, and DC.
See this image and copyright information in PMC

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