Immune engineering for the treatment of childhood acute lymphoblastic leukemias

• Grant number: 14/04412-4
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2014
• End date: October 31, 2017
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Pedro Otavio de Campos Lima
• Grantee: Pedro Otavio de Campos Lima
• Host Institution: Centro Infantil de Investigações Hematológicas Dr Domingos A Boldrini (CIB). Campinas , SP, Brazil
• Associated researchers: Alexandre Eduardo Nowill ; José Andrés Yunes ; Maria Lucia de Martino Lee ; Silvia Regina Brandalise ; Vitória Régia Pereira Pinheiro

Abstract

There has been considerable progress in the approach adopted for the treatment of acute lymphoblastic leukemias over the past decades partly due to the stratification of patients by risk groups. The incorporation of new tools into the therapeutic arsenal, such as rituximab and allogeneic bone marrow transplantation has also contributed to this success. However, an important group of patients still present poor prognosis: mainly those with relapsing acute lymphoblastic leukemia unresponsive to intensive salvage chemotherapy and allogeneic bone marrow transplantation. Thus, there is a clear need to develop new treatments for these patients. Among the alternative options being successfully tested in clinical trials, are various protocols for cancer immunotherapy that capitalize on the proven involvement of the immune system in antitumor surveillance. This project aims to develop a new immunotherapeutic strategy that is based on the ex vivo genetic modification of lymphocytes from cancer patients to give them a designed antitumor specificity. The research activities will address preclinical aspects that precede an eventual phase I clinical trial. We intend to characterize the phenotype of the modified lymphocytes, their proliferative capacity, and their effector function in vitro. We will use mouse models to test the efficacy of antitumor effector cells in vivo. Our approach differs significantly from existing platforms and we believe that it can be more effective. (AU)