Vaccines based on dendritic cells transfected with RNA from tumor biopsies or circulating tumor cells: a new immunotherapeutic strategy in the context of breast cancer?

• Grant number: 22/06056-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2023
• Status: Discontinued
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Jose Alexandre Marzagão Barbuto
• Grantee: Giovanna Manga Guimarães
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 24/22431-8 - Beyond a prognostic factor: uncovering the use of CTCs as a source of tumor RNA for cancer therapy, BE.EP.DR

Abstract

Breast cancer, the main neoplasm that affects women in the world, despite having high cure rates when detected in its initial state still ranks in second among causes for cancer related death in women. Among the current standard-treatment possibilities, chemotherapy and hormone therapy are the ones who stand out the most, however, patients with metastatic, aggressive and/or relapsed disease remain a challenge to clinicians and so, new therapeutic approaches are needed. In this sense, immunotherapy has been considered as an interesting strategy, more specifically, the development of dendritic cells-based vaccines. This kind of therapy considers the high efficiency of dendritic cells for antigen presentation, resulting in T lymphocyte activation and differentiation, allowing the establishment of specific immune responses, including to tumor-related antigens. Thus, considering the current challenges in the field, especially in regard to the few possibilities of treatment for advanced disease cases, the present work focus on the development of a new therapeutic approach for breast cancer. For this, it is aimed to investigate the feasibility of transfecting tumor RNA, extracted from tumor samples of breast cancer patients, into dendritic cells as a strategy for vaccine production. The viability, phenotype and the capacity of the transfected-dendritic cells in inducing an antigen-specific response will be further analyzed in vitro. Additionally, considering the simplification of this approach by making the need of biopsy resection unnecessary, it is intended to evaluate the use of circulating tumor cells as a source of tumor RNA. This personalized strategy would be, therefore, based on a minimally invasive approach. Also, it could be developed concurrently to the patient's clinical evolution and contribute for the establishment of an immunological memory, possibly diminishing the chances of relapses.