“This is one of the first studies in humans to show an effective treatment for cancer with adoptive gene therapy,” said Bert W. O’Malley, Jr., MD, in a phone interview. “Although only two patients responded, the key is that patients did respond. Two of 17 are over 10 percent, which is remarkable considering the deadly nature of melanoma.” Dr. O’Malley, who was not involved in the study, is the Gabriel Tucker Professor and Chair of the Department of Otorhinolaryngology–Head and Neck Surgery at the University of Pennsylvania Health Systems in Philadelphia, where he is the co-director of both the Center for Head and Neck Cancer and the Center for Cranial Based Surgery.
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November 2006
“Gene immunotherapy had not left preclinical studies in head and neck,” he said, noting that it was somewhat understandable that a breakthrough would occur in melanoma. “Melanomas tend to be immune-responsive, unlike squamous cell carcinomas. We still have no data to show whether this approach would be effective in squamous cell carcinoma, or in salivary or thyroid tumors, the most common cancers that we treat.”
Another gene therapy strategy, adoptive gene therapy, uses autologous tumor-infiltrating lymphocytes (TILs). Although this approach is associated with up to a 50% objective response rate, not all patients have harvestable TILs, Dr. Sikora said.
“The unique factor of this study is its novel approach: to take T-cells from the patient’s blood and increase the number of tumor-specific T-cells before injecting them back into the patient,” he said. “It’s a way to help patients whose TILs can’t be harvested, and it’s one of the first cases of using gene therapy against cancer that’s been successful. It’s an important proof-of-principle study.”
Potential to Complement other Approaches
The approach could be used to complement other gene therapy or immunotherapy approaches, Dr. Sikora said. For example, it could be used in combination with vaccine therapy or with a stronger lymphodepletion regimen. Lymphodepletion uses chemotherapy, radiation, or a combination to reduce the number of nonspecific T-cells so that the body’s capacity for cancer-specific T-cells is increased. Adding radiation to the lymphodepletion regimen would be another way to modify the technique to make it more effective, he said.
Dr. Sikora’s and his colleagues’ research is investigating translational work that uses a mouse model of adoptive immunotherapy and vaccination that is similar in many respects to adoptive cell therapy in human trials, and they also are involved in melanoma immunotherapy clinical trials.
Beyond Melanoma
The research involving gene therapy as a way to address melanoma should interest head and neck surgeons, Dr. Sikora said. “This approach may one day improve outcomes in patients with metastatic disease or regional disease at high risk of metastasis,” he said. “It’s just as relevant to head and neck melanoma as it is to melanoma at any other site of the body. We should be involved in this and other gene therapy techniques.”