Exploring therapeutic benefit of immunomodulatory vaccines derived from genetically modified human cells, to potentiate antitumor response in triple negative breast cancer model

• Grant number: 23/12245-0
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2024
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Marcio Chaim Bajgelman
• Grantee: Marcio Chaim Bajgelman
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil
• Associated scholarship(s): 25/02507-2 - Investigation of the terapeutical efects of immunomodulatory vaccines, derived from human cells modified with viral vectors, to poencialize antitumoral response in human triple negative breast cancer model, BP.TT; 25/01083-4 - Tecnical practice in animal experiment, BP.TT; 24/13185-3 - training in molecular biology and cell culture, BP.TT

Abstract

Triple negative breast cancer is characterized by the absence of estrogen, progesterone receptors and low production of the her-2 protein. In this way, hormonal therapies or anti-her2 targeted immunotherapy are ineffective. The available treatment is based on surgical removal, radiotherapy, chemotherapy and currently new protocols have also been explored with the use of PD1 checkpoint inhibitor antibodies. Nevertheless, existing therapies are not effective in many cases, which justifies the investigation of new strategies that could benefit non-responsive individuals. Immunomodulatory therapeutic vaccines can be used to enhance the antitumor response, such as the treatment of prostate cancer with the personalized drug Sipuleucel-T, which derives from autologous dendritic cells, pulsed with a tumor antigen and the GM-CSF protein. Previous data from our group demonstrate that vaccine combinations of immunomodulators that act on the co-stimulation of T cells and activation of presenting cells can strengthen antitumor immunity, stimulating an increase in lymphocytic infiltrate, a reduction in regulatory T cells and also providing long-term protection in immunocompetent animal models challenged with syngeneic tumors. In this project, we aim to investigate the use of antitumor vaccines derived from triple-negative human breast cancer cells, genetically modified with viral vectors, derived from lentiviruses and adenoviruses, for the expression of the immunomodulators 4-1BBL, OX40L and GM-CSF. We will evaluate the effect of vaccine monotherapies and combinations, by cell culture and also using a humanized animal model. The success of the project may provide new insights to the research and development of therapeutic strategies for the treatment of triple negative human breast cancer. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ROSA, RHUBIA S. M.; PALAMETA, SOLEDAD; TOSCARO, JESSICA M.; MILLER, MICHAEL E.; LOPES-DE-OLIVEIRA, PAULO S.; BAJGELMAN, MARCIO C.. Harnessing endogenous miRNA targeting ZIKV: A cutting-edge strategy to inhibit virus infection. MOLECULAR THERAPY-NUCLEIC ACIDS, v. 36, n. 2, p. 12-pg., 2025-06-10. (21/09107-9, 23/12245-0)