gamma delta T cells for cancer immunotherapy A systematic review of clinical trials

gamma delta T cells contribute to the front line of lymphoid antitumor surveillance and bridge the gap between innate and adaptive immunity. They can be readily expanded to high numbers in vivo and in vitro, starting from the blood of cancer patients, and a number of Phase I trials have demonstrated that these cells can be employed in cancer immunotherapy. Sufficient patients have received gamma delta T cell-based immunotherapies in the context of clinical trials to evaluate their utility, and to inform the direction of new trials. A systematic approach was used to identify Phase I, Phase II, and feasibility studies testing gamma delta T cell-based immunotherapy in cancer patients. Studies were excluded from further analysis if they did not provide patient-specific data. Data were compiled to evaluate efficacy, with stratification by treatment approach. When possible, comparisons were made with the efficacy of second-line conventional therapeutic approaches for the same malignancy. Twelve eligible studies were identified, providing information on 157 patients who had received gamma delta T cell-based immunotherapy. The comparison of objective response data suggests that gamma delta T cell-based immunotherapy is superior to current second-line therapies for advanced renal cell carcinoma and prostate cancer, but not for non-small cell lung carcinoma. An evaluation of pooled data from 132 published in vitro experiments shows a consistent improvement in the cytotoxicity of gamma delta T cells in the presence of antitumor antibodies. Immunotherapy using gamma delta T cells alone shows promising clinical activity, but there is a strong preclinical rationale for combining this treatment modality with cancer-targeting antibodies to augment its efficacy.