Background
Cancer prevention and early detection are the first two of the eight primary goals of the National Cancer Plan released in April 2023. The NCI PREVENT cancer preclinical drug development program is a peer-reviewed program that provides partnership opportunities to extramural researchers, who are interested in advancing innovative cancer preventive interventions and biomarkers towards clinical trials (https://prevention.cancer.gov/major-programs/prevent-cancer-preclinical). One of the program’s major scientific focus areas is cancer immunoprevention and immunointerception. Mounting evidence strongly suggests that the immune system can be harnessed to elicit durable antitumor immunity, for example through cancer vaccines and immunomodulatory agents, which can intercept, arrest, and/or reverse the oncogenic process. This strategy is more effective before invasive cancer develops.
Methods
PREVENT utilizes NCI contract resources to operate its agent development pipeline, which consists of three key stages: confirmation of activity phase, optimization of agents and regimens phase, and advanced preclinical development and IND-enabling study phase. Competitively selected contractor pools with necessary technical expertise are in place to implement approved projects under NCI oversight. Data and materials generated through PREVENT are returned to the applicant researchers for further agent development. A wide array of organ-specific preclinical cancer models is available to assess agent efficacy and toxicity as well as agent production and regulatory support.
Results
Since the Program’s inception, a total of 34 immunoprevention projects have been selected for support. Of those, two vaccines have progressed to the clinical trial stage with two additional projects in the advanced development phase. The PREVENT immunoprevention portfolio includes a variety of vaccination approaches, such as recombinant protein-, peptide-, DNA-, and RNA-based vaccines, targeting oncogenic drivers, early tumor associated antigens, and oncogenic pathogens such as Fusobacterium nucleatum. These vaccines are developed for clinically identifiable high-risk cohorts, including those who have been exposed to carcinogens (e.g., former or current smokers), genetically predisposed populations (e.g., individuals with Lynch syndrome, BRCA1/2 mutations, and familial adenomatous polyposis, etc.) and those diagnosed with pre-cancerous lesions.
Conclusions
While the expanded knowledge base in tumor immunology has uncovered the potential hurdles for developing effective cancer immunoprevention strategies, it has also helped better understand the key determinants, including the selection of optimal antigenic epitopes, vaccine delivery and scheduling strategies, relevant adjuvant selection process, immune biomarkers for vaccine immunogenicity and immune durability assessment, and immune correlates of antitumor protection. PREVENT seeks researchers interested in developing novel cancer vaccines and immunomodulatory agents toward clinical applications.