Developing an Effective Breast Cancer Vaccine

Hatem Soliman, MD

Disclosures

Cancer Control. 2010;17(3):183-190. 

In This Article

Abstract and Introduction

Abstract

Background: Harnessing the immune response in treating breast cancer would potentially offer a less toxic, more targeted approach to eradicating residual disease. Breast cancer vaccines are being developed to effectively train cytotoxic T cells to recognize and kill transformed cells while sparing normal ones. However, achieving this goal has been problematic due to the ability of established cancers to suppress and evade the immune response.
Methods: A review of the literature on vaccines and breast cancer treatment was conducted, specifically addressing strategies currently available, as well as appropriate settings, paradigms for vaccine development and response monitoring, and challenges with immunosuppression.
Results: Multiple issues need to be addressed in order to optimize the benefits offered by breast cancer vaccines. Primary issues include the following: (1) cancer vaccines will likely work better in a minimal residual disease state, (2) clinical trial design for immunotherapy should incorporate recommendations from expert groups such as the Cancer Vaccine Working Group and use standardized immune response measurements, (3) the presently available cancer vaccine approaches, including dendritic cell-based, tumor-associated antigen peptide-based, and whole cell-based, have various pros and cons, (4) to date, no one approach has been shown to be superior to another, and (5) vaccines will need to be combined with immunoregulatory agents to overcome tumor-related immunosuppression.
Conclusions: Combining a properly optimized cancer vaccine with novel immunomodulating agents that overcome tumor-related immunosuppression in a well-designed clinical trial offers the best hope for developing an effective breast cancer vaccine strategy.

Introduction

The notion of cancer immunotherapy is hardly new. Associations between tumor regressions and infections date back to the 1700s. In 1893, Coley[1] reported injecting sarcomas with Gram-positive bacteria to induce a local inflammatory response and subsequent tumor regression. Subsequent breast cancer chemoimmunotherapy trials performed at the M.D. Anderson Cancer Center in the 1970s combined bacillus Calmette-Guérin (BCG) injections with 5-fluorouracil-Adriamycincyclo phosphamide (FAC) chemotherapy.[1,2] Responding patients who received BCG injections plus FAC had longer periods of progression-free and overall survival than those treated with FAC alone. The field has advanced considerably since then, with an increased understanding of candidate antigens, adjuvants, tumor-related immunosuppression pathways, and techniques. However, this improved understanding has yet to translate into a US Food and Drug Administration (FDA)-approved cancer vaccine for breast cancer.

While breast cancer cure rates with current multimodality therapy have improved, an estimated 20% to 30% of patients will have a recurrence of their disease. A safe, effective breast cancer vaccine strategy may reduce this recurrence risk significantly and prevent more costly palliative treatments later on. Several reviews have discussed the scientific rationale and data behind specific breast cancer vaccines.[3,4] There are many promising candidates, but the main challenges will be to properly select the vaccines that offer the greatest clinical benefit and to implement these treatments on a large scale. This article provides an overview of these considerations and attempts to put them into perspective.

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