Hybrid dendritic-tumor cell immunotherapy in dogs with solid neoplasia: emphasis on immunogram and liquid biopsy evaluation

• Grant number: 20/01004-3
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2020
• End date: June 30, 2022
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Cristina de Oliveira Massoco Salles Gomes
• Grantee: Cristina de Oliveira Massoco Salles Gomes
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• City of the host institution: São Paulo
• Associated researchers: Jose Alexandre Marzagão Barbuto

Abstract

This project aims to verify the clinical outcome of an experimental immunotherapy associated with conventional treatments used in veterinary oncology and to evaluate the influence of the immunological context represented by an "immunogram" as a predictive factor in the clinical response of dogs with solid neoplasia. It will be based on a prospective clinical safety study comparing survival time between groups and those described in the literature for the malignancies included in this study. Patients will be allocated according to the presence or absence of metastasis and association with conventional therapies, namely: 1- surgery + dendritic cell hybrid vaccine + electrochemotherapy (no metastasis = VDCEqM-) (n = 10); 2- surgery + electrochemotherapy + dendritic cell hybrid vaccine (with metastasis = VDCEqM +) (n = 10); 3- surgery + electrochemotherapy + tumor lysate vaccine (no metastasis = VLiEqM-) (n = 10) and 4- surgery + electrochemotherapy + tumor lysate vaccine (with metastasis = VLiEqM +) (n = 10). To assess toxicity, physical examinations will be performed to evaluate the application site and, for a systemic evaluation, laboratory tests will be performed (blood count, renal and hepatic profile). To assess the clinical response, patients will be followed by physical, imaging and screening of circulating tumor cells using the liquid biopsy technique based on the physical properties of cells by comparing the quantification of circulating tumor cells before and after. during treatment. The evaluation of antitumor immune response will be performed by an "immunogram" based on a multivariate analysis of circulating blood biomarkers which will be correlated with disease and survival free time, namely: 1- the immunophenotypic profile obtained from the frequency of cytotoxic T lymphocytes (CTL), regulatory T lymphocytes (Treg) and blood suppressive myeloid cells (MSDCs); 2- the inflammatory profile by measuring neutrophil lymphocyte ratio (NRL), platelet lymphocyte ratio (PLR), monocyte lymphocyte ratio (MLR) and inflammatory systemic index immune system inflammation (SII) obtained by blood count; 3- levels of serum cytokines IFN-gamma, IL-2, IL-12 and IL-10 and 4- serum levels of lactate dehydrogenase (LDH). This project seeks to contribute new perspectives to the development of an active antineoplastic therapy aiming at increasing the therapeutic chances for patients refractory to conventional therapies and to demonstrate that the clinical benefit has been achieved due to the induction of an effector immune response. (AU)