Current status of autologous breast tumor cell-based vaccines

Abstract

Approximately nine out of ten breast cancer-related deaths are attributable to metastasis. Yet, less than 4% of breast cancer patients are initially diagnosed with metastatic cancer. Therefore, the majority of breast cancer-related deaths are due to recurrence and progression of non-metastatic disease. There is tremendous clinical opportunity for novel adjuvant strategies, such as immunotherapies, that have the potential to prevent progressive recurrences. In particular, autologous tumor cell-based vaccines (ATCVs) can train a patient’s immune system to recognize and eliminate occult disease. ATCVs have several advantages including safety, multivalency and patient specificity. Furthermore, because lumpectomy or mastectomy is indicated for the vast majority of breast cancer patients, resected tumors offer a readily available, patient-specific source of tumor antigen. Disadvantages of ATCVs include poor immunogenicity and production inconsistencies. This review summarizes recent progress in the development of autologous breast tumor vaccines and offers insight for overcoming existing limitations.

Keywords::

• autologous vaccine
• breast cancer
• cell-based vaccine
• immunotherapy
• tumor vaccine

Financial & competing interests disclosure

This report was supported by grants from the National Institutes of Health (R01CA172631, R15CA176649) and the Arkansas Breast Cancer Research Programs. The University of Arkansas for Medical Sciences Translational Research Institute (CTSA Grant Award # UL1TR000039) provided resources during the review and selection process. The authors have no relevant affiliation or involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

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

Key issues

• Approximately 40,000 women will die from breast cancer in the US in 2014. The vast majority of these deaths are due to progressive recurrences of non-metastatic breast cancer.

• Current adjuvant therapies, in addition to being toxic, fail to protect against recurrence in tens of thousands of breast cancer patients each year.

• ATCVs have a number of advantages as an adjuvant therapy for breast cancer, including being multivalent, patient-specific and safe.

• Several clinical trials in breast cancer and other cancers have demonstrated that ATCVs are safe and effective in extending survival for some cancer patients.

• Preclinical studies show that insertion of genes expressing IL-2, MHC II, B7.1 or Staphylococcal aureus enterotoxin B can enhance the immunogenicity of tumor cells and lead to their effective use as therapeutic vaccines.

• Investments in preclinical research aimed at overcoming key obstacles will likely help ATCVs achieve widespread clinical application as an adjuvant therapy for breast cancer.