The key to immune-based cancer therapies lies in the ability to exploit some weakness within the tumor and its environment or to elude cancer’s offenses. Researchers led by a group from the Roswell Park Cancer Institute (RPCI) Center for Immunotherapy have shared new insights about a subset of T cells that appear to do both those things, inhibiting cancer growth at the same time that they enhance the tumor-killing powers of 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 (pictured top), 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 (pictured middle), 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 (pictured bottom), 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.
Illustration: Roswell Park Cancer Institute.
Roswell Park Cancer Institute News Release (10/15/15)
Science Daily (10/15/15)
Abstract (Scientific Reports; 5, 14896 (10/08/15))