HER-2 dendritic cell vaccine linked to tumor eradication

Koski GK. J Immunother. 2012;35:54-65.

A course of vaccination with an anti–HER-2 dendritic cell vaccine created from a patient’s own cells triggered complete tumor eradication in 18% of women with ductal carcinoma in situ, according to an article published in the Journal of Immunotherapy.

Researchers at the Perelman School of Medicine at the University of Pennsylvania formulated an integrated dendritic cell-based immunization system, in which they obtained peripheral blood monocytes from ductal carcinoma in situ (DCIS) patients, then isolated and activated into fully functional dendritic cells in vitrowith interferon and the clinical-grade bacterial endotoxin lipopolysaccharide. As key regulators of the immune systems, the dendritic cells would be primed with HER-2/neu protein and administered directly to the lymph nodes of the patient with the expectation the activated dendritic cells would treat the tumor as an infection.

To assess the effectiveness of the system, researchers conducted a safety and immunogenicity trial of a HER-2/neu-based dendritic cell immunization strategy for patients with HER-2/neu overexpressing DCIS. Twenty-seven patients with HER-2–positive DCIS were enrolled in the study to receive dendritic cell vaccinations intranodally four times in weekly intervals. Surgical resection of the remaining tumor occurred after vaccinations had been terminated.

According to the study results, 18% (5/27) of the patients exhibited no evidence of remaining disease during surgical observation. Among patients who continued to demonstrate residual DCIS, expression of the HER-2/neu protein was observed to have been eradicated in 50% (11/22). After comparing ER-negative with ER-positive DCIS lesions, vaccination was observed to be more effective in hormone-independent DCIS. After vaccination, no residual DCIS was found in 40% of ER-negative patients compared with 5.9% of ER-positive patients.

In addition, sustained HER-2/neu expression was found in 10% of ER-negative patients compared with 47.1% of ER-positive patients (P=.04).

“I think these data more than prove that vaccination works in situations where the target is right,” researcher Brian Czerniecki, MD, PhD, surgical director of the Rena Rowan Breast Center at the University of Pennsylvania and surgical director of the immunotherapy program for the Abramson Cancer Center, said in a press release. “Previous vaccines targeted tissue antigens that were expressed on the cancer cells but were not necessary for tumor survival. So a vaccine response would cause the tumor to just stop expressing the antigen and the tumor would be fine. Here we’re going after HER-2/neu, which is critical for survival of early breast cancers. If we knock it out with the immune response, we cripple the tumor cells.”

Disclosure: The researchers report funding support from the National Institutes of Health R01 CA096997, the Harrington Foundation, Pennies-in-action.org and the Mistler Foundation.

Earn CME this spring at the HemOnc Today Breast Cancer Review & Perspective meeting to be held March 23-24, 2012 at the Hilton San Diego Bayfront. See details at HemOncTodayBreastCancer.com.

Adam M. Brufsky, MD

These are very interesting data as a proof of concept that Her2 pulsed DC vaccinations can impact the presence of Her2 (+) DCIS. It is interesting that the ER positive DCIS in the Cancer manuscript was not affected greatly by the vaccination, and still overexpressed Her2. Finally, these procedures are somewhat cumbersome for prevention purposes. Interestingly, there is an ongoing adjuvant protocol, NSABP B43, which treats women with two doses of traztuzumab during radiation therapy. DFS is the primary endpoint. These proof of concept studies give us some hope that B43 may in the end turn out to be a positive trial as secondary prevention. Perhaps someday a simplified Her2 vaccine could be used as prevention as well.

Adam M. Brufsky, MD, PhD
HemOnc Today Editorial Board member

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