Development and characterization of antitumor vaccines derived from adenovirus-modified human triple-negative Breast Cancer cells encoding TNFSF immunomodulators and GM-CSF cytokine

• Grant number: 23/11023-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2024
• End date: June 30, 2026
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Marcio Chaim Bajgelman
• Grantee: Karina Danielle Pereira
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil

Abstract

Cancer is a multifactorial disease, in which cells acquire mutations, that may lead to proliferative advantages that allow their establishment and escape from the immune system. The therapeutic strategies developed for the treatment of cancer are based on surgery, radiotherapy, chemotherapy, and immunotherapy. Immunotherapy has revolutionized clinical oncology, enabling the treatment of individuals who do not respond to chemotherapy. In the case of triple-negative breast cancer, that cells are deficient in progesterone and estrogen receptors and exhibit low Her-2 expression, treatment with existing therapies does not present a good prognosis, justifying the exploration of new approaches. The use of monoclonal antibodies to inhibit immunological checkpoints has been explored in therapeutics, showing promising results. In this project, we propose to investigate a new antitumor strategy driven to triple negative breast cancer cells using antitumor vaccines, to enhance the infiltration of immune cells and strengthening the antitumor response. In this sense, our proposal is to develop and characterize recombinant adenoviral vectors that harbor immunomodulators, as TNFSF 4-1BBL, OX40L and the cytokine GM-CSF. TNFSF immunomodulators act in lymphocyte costimulation, and the cytokine GM-CSG contributes to the activation of presenting cells. Previous data from our group, using syngeneic animal models, challenged with low-immunogenic tumors, demonstrate that vaccine combinations with these immunomodulators induce a potent and long-term antitumor response. Therefore, we plan to explore the development of antitumor vaccines derived from human cells, genetically modified with adenoviral vectors encoding these human immunomodulators, evaluating the effectiveness of the strategy using in vitro models and humanized animals. The results of this project may contribute to the development of new therapeutic approaches for the treatment of human cancer. (AU)