Special class of T cells shown to both attack cancer cells and enlist other immune cells

The researchers identified a subset of CD4+ "helper" T cells that they call "tumor-recognizing CD4+ T cells" or TR-CD4 because of their unique ability to recognize and respond to cancer cells. These special CD4+ T cells are antigen-specific: they recognize the tumor antigen NY-ESO-1, which is expressed by many solid tumors, including ovarian, melanoma, prostate, lung, breast and synovial sarcoma cancers.

"While most studies today involving adoptive T-cell immunotherapy focus on CD8+ 'killer' T-cells, our team's findings highlight a significant role for CD4+ 'helper' T cells, which can also play a central role in promoting antitumor immune responses," says Kunle Odunsi, MD, PhD, Cancer Center Deputy Director, Executive Director of Roswell Park's Center for Immunotherapy and senior author on the new study.

In preclinical studies involving models of human ovarian cancer and melanoma, the TR-CD4 cells proved to be potent inhibitors of cancer growth, working both alone and in collaboration with CD8+ T cells. Conventional CD4+ T cells, meanwhile, showed no such effects.

The findings help explain the robust immune responses generated through vaccination with an NY-ESO-1 peptide in earlier preclinical studies, and add further evidence to suggest that adoptive T cell therapy targeting the NY-ESO-1 antigen may have strong and lasting efficacy.

"We also demonstrated that we can generate a large number of these special T cells, TR-CD4, from a patient's blood by gene engineering in a matter of days, and we expect that when we infuse these re-engineered cells back into the patient, they will recognize and attack tumors," says the paper's first author, Junko Matsuzaki, PhD, Assistant Professor of Oncology and Director of the Immune Analysis Facility within the Roswell Park Center for Immunotherapy.

"Our findings suggest that this approach -- gene-engineered TR-CD4 gene transduction in combination with CD8 adoptive T-cell therapy -- holds great promise as a cancer immunotherapy, one that may have benefit for patients with several types of cancer," adds Takemasa Tsuji, PhD, Assistant Professor of Oncology and co-corresponding author of the study.

The researchers are now designing a clinical research study to further develop and assess these concepts.