New Task Order Request for Proposal Solicitation for PREVENT R&D Project Titled "Triple Negative Breast Cancer Vaccines"

This Task Order (TO) aims to continue testing the safety and efficacy of RNA cancer vaccines specifically designed for women who are at risk of developing triple negative breast cancer (TNBC). The encoded RNA sequences of vaccine antigens are directly derived from human sequences that have high homology with other species including mice, which will be used for preclinical testing. Patients with TNBC are faced with grim clinical outcomes compared to those with other breast cancer subtypes because TNBC is an aggressive subtype of breast cancer. It accounts for 30-40% of all breast cancer-related deaths. Currently, there are no effective strategies that can prevent or intercept early cancer formation and progression in individuals at risk of developing TNBC, such as those with BReast CAncer gene 1 (BRCA1) mutations. Safe and efficacious TNBC-preventive or interceptive cancer vaccines are urgently needed especially for these high-risk individuals. The TO study is building on the previous work that has clearly shown the superior efficacy of the RNA cancer vaccines than the conventional peptide-based vaccines in a mouse model of TNBC, thus demonstrating a great potential for clinical applications. This TO will carefully determine the safety, confirm the efficacy of the candidate RNA cancer vaccines, and establish the optimal vaccination schedules and immune parameters of human efficacy, all of which will guide future clinical trial planning. The proposed TO project is expected to be completed in 24 months. Lack of continuity of the current cancer vaccine study, which was initiated under the previous TO (TO# 75N91024D00005-75N91024F00002), will stop the progress of the development of urgently needed efficacious cancer vaccines for women at risk of TNBC. If successfully completed, the data from the TO project can lead to new clinical trials which can ultimately form the basis for improving the lifetime outlook for women who are living with fear of developing TNBC. Clinical translation of these candidate cancer vaccines to clinical trials and subsequent clinical practice would not be possible, should this TO not be approved and funded.