Reviews & Reports

News From The AACR’s Frontiers In Cancer Prevention Research Meeting

Novel Vaccine Shows Promise in Breast Cancer

Reviewed by Nicholas J. Vogelzang, MD

Investigators have identified multiple genetic targets that may help fight breast cancer, including BRCA, estrogen receptors, and HER-2/neu, which can predict the severity of the disease, recurrence, and overall survival. Developing novel therapies that target these specific genetic variances may be helpful in preventing breast cancer in many women.

“We are confident that targeted treatment with this vaccine may effectively fight not only DCIS, but may extend to prevention of breast cancer entirely.”

A recent small study reported at the AACR’s Frontiers in Cancer Prevention Research Meeting, held in Boston in November 2006, investigated an candidate vaccine that targets HER-2/neu overexpression in early-stage breast cancer (ductal carcinomas in situ [DCIS]). An estimated 50% to 60% of DCIS is directly related to HER-2/neu overexpression.

Patients with HER-2/neu overexpressing DCIS were given neoadjuvant therapy of autologous dendritic cells (DCs) that were polarized to secret high levels of IL-12 pulsed with HER-2/neu to evoke an immune response. The study participants received 4 weekly vaccinations into normal lymph nodes in the groin area and were evaluated both pre- and postvaccination for immune response, level of HER-2/neu expression, and cell infiltrates.

Most patients had a good response to the vaccine. Eleven of 12 (92%) demonstrated an initial immune response (shown by the presence of anti-HER-2/neu specific CD4+ T cells), and CD8+ T cells with the ability to recognize HER-2/neu-expressing breast cancer. In addition, many developed complement-fixing antibodies against the HER-2/neu cells that could sometimes be detected binding to the DCIS lesions. Patients began to build up white blood cell reserves post-treatment and appeared to develop long-term immune responses to HER-2/neu as a result of the vaccine therapy. Of the 12 study participants, 6 (50%) showed markedly reduced levels of HER-2/neu expression following vaccination; as a result, there was an improvement in their disease severity.

“The results demonstrate for the first time that this dendritic cell vaccination may have significant clinical activity against certain types of breast cancer,” said Brian J. Czerniecki, MD, PhD, of the University of Pennsylvania, Philadelphia, who led the study. “We are confident that targeted treatment with this vaccine may effectively fight not only DCIS, but may extend to prevention of breast cancer entirely,” he noted.

The fact that the DCs administered have the potential to produce a second burst of interleukin-12 following administration when they encounter activated CD4+ T cells makes this approach appealing for use in other cancers such as melanoma, according to Dr. Czerniecki. These DC1 vaccines are activated by toll-like receptors that make them resistant to many of the immune suppressive mechanisms at play in cancer patients and the tumor environment. The investigators currently are finalizing a similar vaccine using these DC1 to treat patients with melanoma. “It is anticipated that such DC1 vaccines can be manipulated with other antigens to use in therapy for other cancers as well, especially in the early primary disease before the tumor may be removed,” Dr. Czerniecki told Advances in Targeted Cancer Therapies.

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Reviews & Reports

News From The AACR’s Frontiers In Cancer Prevention Research Meeting

Novel Vaccine Shows Promise in Breast Cancer