Novel Cancer Vaccine Shows Promise in Ovarian Cancer and Mesothelioma
A novel approach to cancer immunotherapy may provide a new and cost-effective strategy against ovarian cancer and mesothelioma. In a study published in the Journal of Hematology & Oncology, Yuan et al reported that a fusion protein engineered to combine a molecule targeting a tumor-cell-surface antigen with another protein that stimulates several immune functions prolonged survival in animal models of both tumors.
"Some approaches to creating cancer vaccines begin by extracting a patient's own immune cells, priming them with tumor antigens, and returning them to the patient, a process that is complex and expensive," said Mark Poznansky, MD, PhD, Director of the Massachusetts General Hospital Vaccine and Immunotherapy Center and senior author of the report. "Our study describes a very practical, potentially broadly applicable, and low-cost approach that could be used by oncologists everywhere, not just in facilities able to harvest and handle patient's cells."
Fusion Protein Activates Immune Cells Against Tumors
The Jantibody fusion protein, which combines an antibody fragment targeting an antigen found on tumor cells with an immune response–inducing protein (MTBhsp70), activates dendritic cells against several tumor antigens and induces a number of T-cell–based immune responses.
The approach developed by the research team starts with the engineered protein, which in this case fuses an antibody fragment targeting mesothelin—expressed on the surface of such tumors as mesothelioma, ovarian cancer, and pancreatic cancer—to a protein from the tuberculosis bacteria that stimulates the activity of dendritic and other immune cells. In this system, the dendritic cells are activated and targeted against tumor cells while remaining inside the patient's body.
In the study, the investigators confirmed that their mesothelin-targeting fusion protein binds to mesothelin on either ovarian cancer or mesothelioma cells, activates dendritic cells, and enhances the cells' processing and presentation of several different tumor antigens, inducing a number of T-cell–based immune responses. In mouse models of both tumors, treatment with the fusion protein significantly slowed tumor growth and extended survival, probably through the activity of cytotoxic CD8 T cells.
Potentially Safe and Cost-Effective Approach
"Many patients with advanced cancers don't have enough functioning immune cells to be harvested to make a vaccine, but our protein can be made in unlimited amounts to work with the immune cells patients have remaining," explained study coauthor Jeffrey Gelfand, MD, Senior Scientist at the Vaccine and Immunotherapy Center. "We have created a potentially much less expensive approach to making a therapeutic cancer vaccine that, while targeting a single tumor antigen, generates an immune response against multiple antigens. Now if we can combine this with newly described ways to remove the immune system's ‘brakes’—regulatory functions that normally suppress persistent T-cell activity—the combination could dramatically enhance cancer immunotherapy."
Dr. Poznansky added that the tumors that might be treated with the mesothelin-targeting vaccine—ovarian cancer, pancreatic cancer, and mesothelioma—are all associated with poor survival rates. "Immunotherapy is generally nontoxic, so this vaccine has the potential of safely extending survival and reducing the effects of these tumors, possibly even cutting the risk of recurrence. We believe that this approach could ultimately be used to target any type of cancer and are currently investigating an improved targeting approach using personalized antigens."
Dr. Poznansky is the corresponding author for the Journal of Hematology & Oncology article. The study was dedicated to Janet Gelfland, wife of Jeffrey Gelfand, who died of ovarian cancer and inspired the investigation.
The study was funded by grants from the Edmund Lynch Jr Cancer Fund, Arthur Luxenberg Esq, Perry Weitz Esq, the VIC Mesothelioma Research and Resource Program, and the Friends of VIC Fund. The study authors reported no potential conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
