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A study of the role of neoantigens in the modulation of the anti-tumor response promoted by the treatment of B16 cells with p19Arf and IFN-beta.

Grant number: 17/25290-2
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): November 01, 2018
Effective date (End): March 09, 2022
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal Investigator:Bryan Eric Strauss
Grantee:Nayara Gusmão Tessarollo
Host Institution: Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). Coordenadoria de Serviços de Saúde (CSS). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated research grant:15/26580-9 - Cancer gene therapy: strategic positioning for translational studies, AP.TEM

Abstract

Melanoma is the most aggressive type of skin cancer and has a high lethality. A growing number of works have shown the relevance and benefits of gene therapy in treating cancer, including melanoma. In this context, recent research points to vaccination involving neoantigens as a promising strategy in the treatment of this malignancy. Previous results from the research group conducted by Professor Bryan Strauss at the Viral Vector Laboratory (ICESP) have shown that the combined gene transfer of p19Arf and IFN² acts with synergism on the immune system promoting the attraction of neutrophils, natural killer cells and CD4+ T lymphocytes and CD8+, in addition to modulating the expression of genes involved in important cell signaling pathways such as the p53 pathway. However, the mechanisms of activation of the immune system have not been fully elucidated. Thus, we theorize that treatment with the adenoviral vectors may alter the expression of the neoantigens and these may present an important role in the induction of the immune response. Since there are already published articles that describe the neoantigens important for the lineage B16, we will start by evaluating alterations in the expression of these neoantigens upon treatment with the adenoviral vectors p19Arf and IFN², as well as their participation in the antitumor immune response. In addition, we seek to reveal the performance of these neoantigens as vaccinogenic agents when associated with treatment with p19Arf and IFN². This association is expected to provide regression of metastatic tumors in murine models of melanoma immunotherapy.

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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)
TESSAROLLO, NAYARA GUSMAO; DOMINGUES, ANA CAROLINA M.; ANTUNES, FERNANDA; DOS SANTOS DA LUZ, JEAN CARLOS; RODRIGUES, OTAVIO AUGUSTO; DUTRA CERQUEIRA, OTTO LUIZ; STRAUSS, BRYAN E.. Nonreplicating Adenoviral Vectors: Improving Tropism and Delivery of Cancer Gene Therapy. CANCERS, v. 13, n. 8, . (17/25290-2, 17/23068-0, 17/25284-2, 18/25555-9)
LUZ, JEAN CARLOS DOS SANTOS DA; ANTUNES, FERNANDA; CLAVIJO-SALOMON, MARIA ALEJANDRA; SIGNORI, EMANUELA; TESSAROLLO, NAYARA GUSMAO; STRAUSS, BRYAN E.. Clinical Applications and Immunological Aspects of Electroporation-Based Therapies. VACCINES, v. 9, n. 7, . (17/25290-2)
LANA, M. V. G.; ANTUNES, F.; TESSAROLLO, N. G.; STRAUSS, B. E.. Stable expression of shRNA for the control of recombinant adenovirus replication. Brazilian Journal of Medical and Biological Research, v. 56, p. 8-pg., . (18/04800-5, 17/25290-2, 12/05066-7, 15/26580-9)

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