Rendering of combination pembrolizumab (green form at top center) and T-VEC (green circles with red centers) in action. Image: Courtesy of UCLA Jonsson Comprehensive Cancer Center
In a two-year study at UCLA, nearly two-thirds of people with advanced melanoma responded positively to a treatment that combines the immunotherapy drug pembrolizumab with a herpes virus called talimogene laherpareovec, or T-VEC. Researchers found that the side effects of the treatment were manageable and comparable to side effects for people who took either pembrolizumab or T-VEC as a standalone treatment.
UCLA scientists are testing the combination of pembrolizumab and T-VEC as a treatment option for people with advanced melanoma who do not fully respond to either treatment separately. T-VEC is a genetically modified version of the herpes simplex virus that causes cold sores but is safe to use. T-VEC already has been approved for the treatment of melanoma, and it works both by directly killing cancer cells and using a protein that attracts immune cells into the cancers.
Pembrolizumab has become a standard-of-care treatment for advanced melanoma, and it also is being used to treat non-small-cell lung cancer; cancers of the head, neck, kidney and bladder; and Hodgkin's disease. It works by taking the “brakes” off the body's immune system, enabling it to attack cancer.
Antoni Ribas, MD, professor of molecular and medical pharmacology and director of the Tumor Immunology Program at the Jonsson Comprehensive Cancer Center, says people whose melanoma does not respond to pembrolizumab often lack a type of T cell called CD8+ in their tumors; the lack of CD8+ cells seems to prevent immunotherapy drugs from working. But the researchers believe those people might benefit from a combination therapy because T-VEC attracts CD8+ immune cells to the tumors, and pembrolizumab allows them to attack the cancer cells.
The phase 1 clinical trial evaluated 21 people with advanced melanoma. Researchers injected patients' melanoma tumors with T-VEC for six weeks and then gave them infusions of pembrolizumab. Sixty-two percent of the patients had a partial or complete response, meaning that their tumors either shrank or were no longer detectable. The combination therapy could provide an alternative treatment for people with melanoma whose tumors don't respond to other therapies. It also is being tested in people with head, neck and colon cancers.
“Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy,” Cell, September 7, 2017
