Table 1.
Strategies for activation of the immune system against breast cancer.
| Class | Mechanism | Examples |
|---|---|---|
| Cytokines | Bind to cytokine receptors to initiate cell signaling pathways and stimulate immune cell trafficking and effector function | Interleukin-2 Interleukin-12 |
| Growth factors | Increase number of circulating granulocytes | G-CSF GM-CSF |
| Toll-like receptor agonists | Bind TLRs to activate antigen-presenting cells (dendritic cells) to upregulate expression of cytokines and co-stimulatory molecules to attract and stimulate effector immune cells (cytotoxic T lymphocytes) | Polyadenylic-polyuridylic acid (Poly A:U) Polyinosinic-polycytidylic acid (Poly I:C) |
| Immune checkpoint inhibitors | Antibody to CTLA-4, PD-1, or PD-L1 molecules releases T cells from inhibitory signals, thereby unleashing cytotoxic T-cell activity | Ipilimumab (CTLA-4 antibody) Nivolumab (PD-1 antibody) Pembrolizumab (PD-1 antibody) Atezolizumab (PD-L1 antibody) Avelumab (PD-L1 antibody) Durvalumab (PD-L1 antibody) |
| Bispecific, multispecific antibodies | Simultaneously interact with a cancer-specific epitope and stimulatory molecule(s) on effector cell(s) | HER2/CD3 bispecific antibodies |
| Adoptive cell transfer | Infusion of T cells stimulated or engineered to have antitumor effector functions | Chimeric antigen receptor (CAR) T cells expressing HER2/neu |
| Oncolytic viruses | Viruses with specific tropism for cancer cells that induce cancer cell death and activate tumor-directed immune responses | JX-594 (pexastimogene devacirepvec) vaccinia poxvirus expressing GM-CSF) |
| Vaccines | Active immunization against tumor-specific antigens | Nelipepimut-S vaccine against HER2/neu |
Therapeutic strategies to harness the innate and adaptive immune system against breast cancer cells include nonspecific immune system stimulation with cytokines, growth factors, and Toll-like receptor agonists, release of T cells from inhibitory PD-L1 signals, use of antibodies to transmembrane tyrosine kinase receptor HER2 to tag HER2+ breast cancer cells for immune-mediated destruction, stimulation of T cells within the HER2+ breast tumor microenvironment, active vaccination or in vitro reprogramming of T cells against HER2/neu, and injection of oncolytic viruses. See text for details.
G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; HER2, human epidermal growth factor receptor 2; TLR, Toll-like receptor.