Breast cancer immunotherapy: monoclonal antibodies and peptide-based vaccines

Abstract

Recently, immunotherapy has emerged as a treatment strategy in the adjuvant setting of breast cancer. In this review, monoclonal antibodies in passive and peptide-based vaccines, as one of the most commonly studied in active immunotherapy approaches, are discussed. Trastuzumab, a monoclonal antibody against HER-2/neu, has demonstrated considerable efficacy. However, resistance to trastuzumab has led to development of many targeted therapies which have been examined in clinical trials. Monoclonal antibodies against immune-checkpoint molecules that are dysregulated by tumors as an immune resistance mechanism are also explained in this review. Additionally, monoclonal antibodies with the ability to target breast cancer stem cells that play a role in cancer recurrence are mentioned. Here, clinical trials of HER-2/neu B and T cells, MUC1 and hTERT cancer peptide vaccines are also presented. In addition, various strategies for enhancing vaccine efficacy including combination with monoclonal antibodies and using different delivery systems for peptide/protein-based vaccine are described.

Keywords::

• breast cancer
• delivery system
• human epidermal growth factor receptor 2/neuregulin
• monoclonal antibody
• peptide-based cancer vaccine

Financial & competing interests disclosure

The authors are grateful to Shahid Beheshti University of Medical Sciences (School of Pharmacy) for their support. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Passive monoclonal antibodies therapies show short half-life and need frequent and prolonged duration of administration. Active immunotherapy can stimulate the adaptive immune system and generate T-cell memory responses, which can potentially cause long-term benefit. However, various vaccines had limited clinical efficacy due to cancer- or treatment-related anergy.

• To circumvent trastuzumab resistance, novel therapeutic strategies including newer tyrosine kinase inhibitors, heat shock protein 90 inhibitors, anti-angiogenic therapies, PI3K and mTOR inhibitors and IGF-1R inhibitors are currently examined in clinical trials.

• Since use of trastuzumab is significantly hampered by cardiac dysfunction, monitoring and minimizing cardiac toxicity is essential in HER-2-targeted therapies.

• Further to HER-2, overexpression of IGF-1 and VEGF receptors occurs in breast cancer (BC). So agents targeting these receptor pathways represent rational approaches in the management of HER-2-positive BC.

• To avoid the tumor- and treatment-mediated immunosuppression, it is suggested to examine the cancer vaccine in adjuvant setting in not heavily pretreated patients with minimal residual disease state.

• HER-2/neu peptide-based vaccines are categorized into B- and T-cell peptide epitopes. T-cell peptide vaccines include CD8⁺ cell (MHC class I-binding) and CD4⁺ T cell (MHC class II-binding) epitopes.

• Dual CD4⁺ (AE37) and CD8⁺ (GP2) T-cell peptide epitopes are applied to evoke a more robust immunity of both CD4⁺ and CD8⁺ T cells.

• The combination of anti-HER-2 vaccine strategy and trastuzumab pre-treatment may lead to avoidance or delay of recurrence.

• Recently, peptide delivery systems including liposome, virosome and nanogel are used in BC immunotherapy to enhance the potency of the tumor-associated antigen.

• An innovative HER-2/neu multi-peptide virosome vaccine was developed. Virosomes, the reconstituted membrane of an enveloped virus, are safe due to lack of nucleocapsid and the genetic material.

Notes