Abramson Cancer Center
Researchers at the Perelman School of Medicine and the Abramson Cancer Center at the University of Pennsylvania reported last month that a short course of vaccination with an anti-Her2 dendritic cell vaccine made partly from the patient’s own cells triggered complete tumor eradication in nearly 20% of women with ductal carcinoma in situ (DCIS). Brian Czerniecki, M.D., Ph.D., surgical director of the immunotherapy program for the Abramson Cancer Center, enrolled 27 women with Her2-positive DCIS in the vaccine study.
The investigators isolated lymphocytes from patients’ blood, then activated dendritic cells, priming them with small segments of the Her2/neu protein. Each patient then received four injections one week apart. After two weeks patients had surgery to remove any remaining disease, the standard of care for DCIS patients.
At surgery, 5 of 27 (18.5%) vaccinated subjects had no evidence of remaining disease. In the 22 subjects with residual DCIS, Her2/neu expression was eradicated in 11 (50%) of them, and reduced by 20 percent or more in another two. “We are continuing to see this pattern in our second, ongoing trial,” Dr. Czerniecki says. When comparing estrogen receptor (ER) negative with ER-positie DCIS lesions, vaccination was more effective in hormone-independent DCIS. After vaccination, no residual DCIS was found in 40% of ER-negative subjects compared with 5.9% in ER-positive patients.
In analyzing patient immune responses, the investigators found that 85% had Her2-reactive CD4 and CD8 T cells. This suggests that the patients developed a robust and relatively complete immune response after vaccination. Some patients maintained their immune responses for as long as 52 months.
“Previous vaccines targeted tissue antigens that were expressed on the cancer cells but were not necessary for tumor survival,” Dr. Czerniecki noted. “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 Her2/neu, which is critical for survival of early breast cancers. If we knock it out with the immune response, we cripple the tumor cells.”
Regarding Herceptin, Dr. Czerniecki told GEN, “Herceptin is an anti-Her2/neu antibody. This autologous vaccine activates anti-Her2 CD4, CD8, and antibodies.” Because of the nature of the vaccine, patients’ immune responses are maintained against Her2. “Herceptin lasts few months and is gone; it is only antibody therapy,” Dr. Czerniecki explained.
“Eventually if we get this working a little better with some combinations such as vaccine plus trastuzumab or lapatinib, this could be a standalone therapy alternative, allowing the immune response to last longer,” Dr. Czerniecki added. “Ultimately the goal is to prevent disease recurrence and avoid radiation therapy.”