Preclinical Development of TVAX: An Advanced Multiantigen Vaccine for Therapy and Prevention of Malignant Mesothelioma
Abstract
Project objective: Malignant mesothelioma (MM) is a cancer caused by exposure to asbestos, a mineral fiber used between the 1930s and 1980s, particularly on naval bases and shipyards. With a latency period of 20 to 50 years, MM-related deaths in the United States are currently on the rise. MM is an extremely aggressive and fatal cancer that is often diagnosed too late for a cure. For such patients, treatment is strictly to ease pain and discomfort and improve quality of life. Efforts to understand the underlying mechanisms of disease progression have shown that certain proteins provide a survival advantage to MM tumors. These proteins are Survivin, Metastasin, Midkine, WT-1, Brachyury, VEGFR2, and FAP. Eliminating tumor cells or tumor-supportive cells that have increased levels of these proteins may lead to novel and more effective cures for MM. Cancer immunotherapy aims to activate the patient s immune system to attack the tumor cells that are responsible for disease. In order for the immune system to attack only the cancer cells and not normal cells, the immune system must recognize unique proteins present only in the tumor. The proteins that we have chosen are overexpressed in MM cancers and poorly expressed in normal tissues. Therefore, they are good candidates to target for MM. We propose to explore vaccination against these proteins as a strategy to induce activation of the immune system against cancerous mesothelioma cells. For this proposal, we designed an advanced vaccine called mTvax that is able to stimulate the immune system against several target proteins. Strong preliminary data suggest that this novel vaccine generates effective anti-cancer responses. In this proposal, we aim to characterize the specific immune responses stimulated by mTvax and evaluate its efficacy in eradicating MM tumors in mice. In addition, we aim to produce a prototype vaccine for human immunization (Tvax) and evaluate its capacity in stimulating immune cells isolated from human donors. This highly innovative project will advance the field of immunotherapy by producing a new-generation vaccine that is robust, efficacious, and safe. Principal Investigator s Career Goals: Dr. Pietro Bertino primary career goal is to become an independent investigator and a translational research scientist focused on the development of treatment and prevention therapies for MM and other cancers. To achieve this goal, he has organized a "scientific career training program" that includes seminars, academic courses, and international meetings. To support his transition from postdoctoral trainee to independent tenure-track researcher, Dr. Bertino has also organized a "professional career training program" to enrich his teaching experience and specific courses in grant writing, public speaking skills, laboratory management, job search skills, and negotiations. By conducting the proposed research, Dr. Bertino will acquire adequate expertise in immunological methodology to successfully design and conduct investigations that will enable him to pursue his goal of becoming an independently funded cancer investigator. Applicability of the Research: As a therapeutic vaccine, Tvax may be used to induce tumor regression in patients with MM at the early stages of disease. In the case of most late-state tumors, chemotherapy or surgery is used to reduce tumor burden. After these treatments, vaccination with Tvax may be applied to stimulate the immune system in killing remaining MM cells. We expect that once the preclinical studies are performed as a part of this proposal, successful strategies could be translated to clinical trials within 5 years. Tvax vaccines may also have the potential to prevent MM. In the prophylactic setting, persons at high risk for developing MM may be vaccinated prior to MM development. If successful, this approach has the potential to change how MM is managed. Instead of treating patients when it is too late, we su
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610357
Entities
People
- Pietro Bertino
Organizations
- Mauna Kea Observatories
- United States Army