Evaluating of immune function of dendritic cell-tumor hybrid: in vitro study with oral melanoma canine

• Grant number: 16/17528-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2016
• End date: November 30, 2017
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Cristina de Oliveira Massoco Salles Gomes
• Grantee: Cícero Júlio Silva Costa
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

An alternative for cancer of difficult treatment has been the developing of antitumor immunotherapeutic vaccines based on dendritic cells (DCs) that come from idea to stimulate a greater response of T cells, thereby inducing a more effective activity against malignant cells. Among these, several studies have shown that vaccination from the fusion of autologous tumor cells with allogeneic DCs generates an adjuvant effect due to break of tolerance already established between immune cells and the tumor. The use of dendritic-tumor hybrid cells has been explored in human medicine and clinical studies with this approach showed promising result in human patients with melanoma and renal cell carcinoma. In veterinary medicine, the development of effective immunotherapies for the treatment of cancer of malignant nature, invasive and with high metastatic potential, for example, oral melanoma in dogs, will benefit both oncological clinical, animal medicine as human medicine, because it is a condition analogous to human melanoma and both share clinical similarities as resistance to radio-chemotherapy treatments. However, tumor evasion mechanisms may negatively modulate DCs function aiming system tolerance. In this context, the clinical use of these vaccines in veterinary medicine has a barrier that is the lack of understanding of evasion mechanisms of tumor cells to this immunotherapeutic approach. Thus, the aim of this study is to analyze the behavior of canine dendritic-tumor hybrid cells in vitro, checking their phenotypic characteristics, ability to induce lymphoproliferation (function) and secretion of cytokines in co-cultures with cells of oral melanoma canine (OMC) and lymphocytes. For this, canine DCs will be differentiated from peripheral blood monocytes of healthy dogs, then the cells obtained will be fused with cells OMC, to continue the phenotypic and function analyzes of DCs. The data obtained from this study can generate information relevant to new therapeutic methods against cancer refractory to conventional treatments. (AU)