Tumor cryoablation coupled with immunotherapy amplifies tumor immunity

Scientists at the Barbara Ann Karmanos Cancer Institute in Detroit today presented data at the American Association for Cancer Research's 102nd Annual Meeting 2011 showing that when tumor cryoablation – or the freezing of tumor tissue while preserving tumor-associated antigens – is coupled with immune system modulation, the procedures have the potential to initiate or amplify tumor immunity.

The title of the poster presentation is, "Amplification of tumor immunity with cryoablation." The presentation was given by Jesse Veenstra, a student in the M.D./Ph.D. program at the Barbara Ann Karmanos Institute and Wayne State University School of Medicine (WSU SOM) and co-author of the study. His fellow authors are Peter Littrup, M.D., radiologist and director of the Imaging Core and Radiological Research at Karmanos and WSU SOM, and Wei-Zen Wei, Ph.D., associate center director of Basic Sciences at Karmanos and professor in the Department of Oncology, WSU SOM.

Veenstra explained that in some cases, tumor cryoablation is capable of inducing an immune response against ablated cancer cells. This immune response has the potential to fight the cancer throughout the entire body. It is, however, not a response that is consistently seen in patients. Karmanos doctors perform tumor ablation mostly for patients who aren't candidates for surgical resection of their tumor due to metastasis of the disease. In these situations, cryoablation is used mostly for decreasing tumor size to promote a patient's physical comfort.

"In most cases, the cancer is fairly far along in its stage," Veenstra said. "What we are trying to accomplish is treating tumors that aren't that far developed and we are hoping to promote an immune response through this process by vaccination. Our goal is to develop a more consistent clinical response to cryoablation. Right now, you can't get that consistent immune upregulation with cryoablation alone."

Researchers are utilizing an exclusive DNA vaccine that was developed at Karmanos to target HER-2 positive breast cancer cells to bolster the effectiveness of cryoablation on metastasized tumors.  HER-2 positive cancer cells are present in about 25 percent of breast cancers and other cancer types such as head and neck cancer, according to Veenstra.

"By using the DNA vaccine, we pre-stimulate the immune system against the antigen of our choice (HER-2 neu) and then when we perform cryoablation, it's a boost against that specific tumor antigen," he said. "It's a more effective cryoablation."

Research was conducted in the laboratory and scientists found that the best results for tumor death and immunity resulted from the combined modalities of DNA vaccine and cryotherapy, in contrast to when these methods were used individually.

Effectiveness, Veenstra noted, is dependent on tumor type, stage and location in the body.

Another component of the research project is the depletion of Tregs (or T regulator cells), which typically inhibit anti-tumor response.

"We use a depleting antibody that recognizes markers fairly specific to those Treg cells," he said. "When you deplete them, you get a better overall immune response. When we did that in conjunction with cryoablation, we did see an improved survival."

Researchers intend to pair Treg depletion with the DNA vaccine in future experiments with cryotherapy.

"We are very excited so far by the results of combining cryotherapy with the DNA vaccine and believe that it will eventually have implications in the clinic," Veenstra said. "We want to use the combination of both so they can synergistically work to create a good systemic immune response that's capable of fighting metastasis and preventing any tumor recurrence. The potential to consistently develop a targeted anti-tumor immune response could offer a substantial benefit to patients."

SOURCE Barbara Ann Karmanos Cancer Institute