Grant: Project Grant

Ovarian cancer is the most fatal gynecological cancer in Canada, largely due to the lack of effective treatments. Recently, a novel type of antibody approach called a Bi-specific T Cell Engager (BiTE) has shown promising preclinical efficacy for treating ovarian cancer. BiTE therapies work directing the patient's own immune cells to the tumors where they can most effectively fight the cancer. While extremely promising, there are roadblocks that prevent widespread use of BiTEs in the clinic. First, they have short half-lives, which means that patients must receive frequent treatments. Second, unlike more common types of antibodies BiTE are more difficult to manufacture. Therefore, we need a novel breakthrough to fully realize the therapeutic potential of BiTE antibodies. Here we propose an approach as new strategy for the treatment of ovarian cancer. We propose to make RNA formulations that allow patients' own cells to act as a bioreactor and manufacture the BiTE antibodies. The strategy is an elegant modification of the mRNA vaccine strategy that allowed billions of people to develop immunity to COVID-19. Our therapy uses a special type of messenger RNA, called self-amplifying RNA (saRNA), which results in longer duration of BiTE expression and requires a much lower dose of RNA. By engineering saRNA BiTE therapeutics we can minimize the frequency of administration of these anti-cancer therapeutics to patients and effectively treat ovarian cancer. Our goal is to optimize the design of saRNA-based therapeutics and deliver them in a way that gives maximal effectiveness in the patient's cells. We will mimic production of the patients own immune molecules and maximizes the magnitude and duration of BiTE production. This preclinical research will generate novel saRNA-launched BiTE therapeutics for the treatment of ovarian cancer to be tested in clinical trials and make BiTE antibody therapies more affordable and accessible for people in Canada and worldwide.