There have been promising results in a few patients with human papillomavirus (HPV)-positive epithelial cancers who were treated with innovative T-cell therapies, according to a study published in the Journal of Clinical Oncology.1
“The idea behind the treatment is to target a constitutively expressed tumor antigen expressed only in tumor cells and not healthy tissue,” said Christian Hinrichs, MD, investigator in the experimental transplantation and immunology branch at the National Cancer Institute, NIH Lasker Clinical Research Scholar, and lead author of the research.
T cells are taken from the patient and genetically engineered to express a T-cell receptor (TCR) targeting an HPV viral oncoprotein expressed on HPV-associated cancers. They are then expanded to huge numbers (up to 100 billion cells) and infused back into the patient.
“The main toxicities are related to the chemotherapy given in the conditioning regimen — cyclophosphamide and fludarabine,” said Dr Hinrichs, noting that these toxicities included bone marrow toxicity, bleeding, and an increased risk of infection.
Any significant clinical benefit of engineered T cells so far has generally been limited to their use in hematological cancers. Why has progress been so slow for other cancer types?
“This approach is similar to [chimeric antigen receptor] CAR T-cell approaches, but the difference is that we don’t use a CAR that can only target antigens on the surface of the cell. We use a TCR that can target intracellular antigens. Many of the most attractive antigens in oncology such as KRAS and BRAF are intracellular, hence, can’t be targeted with CARs,” said Dr Hinrichs.
Two patients enrolled in the trial were described as having an objective response to the therapy, with 1 patient, in particular, having a remarkable response.
“The best response was in a woman with metastatic anal cancer where 1 of her lesions went away completely and another 2 shrank completely. We then operated to remove the residual disease; she’s now 4 years out with no disease. She had metastatic cancer; it’s remarkable and [she] has gone years with no cancer,” said Dr Hinrichs.