Development of a Canine MHC-I neoantigen prediction model in cancer cells

• Grant number: 18/06217-5
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: July 01, 2018
• End date: June 29, 2019
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Heidge Fukumasu
• Grantee: Pedro Ratto Lisboa Pires
• Supervisor: Morten Nielsen
• Host Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
• Institution abroad: Technical University of Denmark (DTU), Denmark
• Associated to the scholarship: 16/19307-7 - Characterization of neoantigens associated to epithelial-mesenchymal transition as potential immunotherapeutic targets, BP.PD

Abstract

Cancer is one of the diseases that concerns the most in human and veterinary medicine taking an important role at scientific research. In 2012, more than 14 million people died of different types of cancer and it is expected that this number increases up to 20 million in 2025. Cancer is responsible for about 50% of deaths of dogs older than 10 years and mammary neoplasias are the most common, corresponding to 52% of the cases. Veterinary oncology it is still fairly timid when compared to human oncology research, however therapeutic target research focused on veterinary cancer diagnosis and prognosis has increased on the past few years. Immunotherapy is one of those therapeutic strategies capable of inducing the immune system to combat cancer cells. Recent immunotherapy approachs based on neoantigens aim to increase antigenicity of imunotherapeutic vaccines to induce the immune response. This propose focuses on detection of neoepitopes exhibition by major histocompatibility complex 1 (MHC1) in canine cancer cells. The project aims to develop and validate a canine MHC epitope prediction model to indentify potential immunotherapeuctic targets in cancer cells. To achieve the aim of the propose, we divided the project in two diferent studies; Study 1, construction of a canine MHC-I prediction model based on MHC-I peptidomic data, and the Study 2, the characterization and validation of the MHC predicting model using a mutation profile based on exome and transcriptome analysis. The development of this technology has a huge impact on veterinary medicine in general and canine immunology in particular since no prediction model has yet been described, focusing on this kind of research. Besides, this technology will improve the way of the immunotherapy against cancer in veterinary medicine, expanding new T Cell-dependent therapies crossing from human to veterinary medicine. (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)

SANTOS, MARIANA RODRIGUES; PORFIRIO XAVIER, PEDRO LUIZ; LISBOA PIRES, PEDRO RATTO; ROCHETTI, ARINA LAZARO; ROSIM, DANIELE FERNANDA; SCAGION, GUILHERME PEREIRA; PIRES DE CAMPOS ZUCCARI, DEBORA APARECIDA; MUNIR, MUHAMMAD; FERREIRA, HELENA LAGE; FUKUMASU, HEIDGE. Oncolytic effect of Newcastle disease virus is attributed to interferon regulation in canine mammary cancer cell lines. VETERINARY AND COMPARATIVE ONCOLOGY, v. 19, n. 3, p. 593-601, SEP 2021. (18/06217-5, 19/05778-6, 16/19307-7, 18/06216-9, 14/02493-7)