Vaccines for Breast Cancer: Real Challenge or Reality?
Walter Sall, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 13, 2003
Faculty Disclosure: Nuhad K. Ibrahim, MD
This presentation by Dr. Ibrahim discusses the use of the STn vaccine for the treatment of breast cancer which has not been approved by the FDA.
Presenter: Nuhad K. Ibrahim, MD
Affiliation: M.D. Anderson Cancer Center
Vaccine mediated cancer therapies are theoretically attractive for many reasons: augmentation of native anti-tumor immunity, specific targeting of tumor antigens, low toxicity enabling combination with cytotoxic chemotherapy, and induction of anti-tumor immunologic memory providing for a surveillance effect. These theoretical benefits have been difficult to realize clinically, though progress has been made. The limitations of vaccine therapies are many and include: the fact that most tumor antigens are self antigens and not tumor specific, that tumors secrete immunosuppressive cytokines, and that anergy may exist limiting T cell amplification.
Several tumor epitopes are currently the targets of vaccine research. These include: CEA, Her2-neu, p53, MUC-1 and STn. STn vaccine is furthest along in the development process. The STn antigen is formed by the aberrant glycosylation of a normally occuring membrane bound polysaccharide. Naturally occuring antibodies to this epitope have been found in breast cancer patients making it a good choice for vaccine development. In clinical trials, synthetic STn is used to immunize patients after pretreatment with low dose cyclophosphamide, the intent of which is to inhibit suppressor T-cells. Phase I/II trials have shown induction of anti-STn IgG antibodies. In the metastatic setting, clinical responses appear to have been seen. A phase III trial is underway, with accrual goal of over 1000 patients.
In order to improve the vaccine, several strategies are being pursued: use of dexasomes to bolster the immunologic response to the vaccine, novel viral vectors to deliver the vaccine epitope and improvement of the inherent immunogenicity of the vaccine epitope. Surrogate endpoints other than survival and tumor response must be developed to help monitor efficacy of these vaccines. One such test is the ELISPOT test.
Future directions of this research will help to determine how vaccines will fit into the standard cytotoxic chemotherapy regimens being used today. It is unclear whether sequential or concommitant use will be best.
Preliminary research shows that breast cancer vaccines have anti-tumor activity and little toxicity. Further investigation is needed to evaluate the magnitude of the benefit and to develop new, more specific and potent vaccine agents.