Development of a new immunoadjuvant for the treatment of glioblastoma: molecule characterization and synthesis, preclinical and translational trials

Abstract

I. Overview: The use of products of natural origin is considered strategic in the context of cancer treatment. It was recently demonstrated that components of the venom of the Phoneutria nigriventer (PnV) spider have antitumor effects in vitro and in vivo models, with emphasis on the modulation of the immune response against glioblastomas. Recently, the composition containing dendritic cells (DCs), tumor cell lysate and an adjuvant peptide isolated from PnV (1600 Da) was the subject of a patent filing by our research group.II. Strategy: Continuing this line of investigation, the present project aims to: 1. Characterize and synthesize the 1600 Da peptide, which has an immunomodulatory effect; 2. Carry out the proof of concept through in vivo assays in a murine model of glioblastoma; and, finally, 3. Perform a translational assay in patients with glioblastoma to confirm the activation of DCs (differentiated from monocytes in the patient's blood) with cell lysate from their own tumor in the presence of the synthesized immunoadjuvant (peptide), which would be a DC vaccine production protocol.III. Integration and feasibility: The integrative strategy of the present proposal involves researchers from different areas. The project development will involve already consolidated collaborations with other research groups, with expertise that complement each other: characterization and synthesis of peptides, basic and applied immunology, study of animal venoms, pre-clinical analyzes in animal models, and a neurosurgery group that will help in the translational step. Therefore, the team enables the execution of all the proposed steps, bringing different areas together in a coordinated manner.IV. Development and social impact: Cancer treatment still represents a major clinical challenge, and glioblastomas are a challenge in their own right. This brain tumor is highly lethal, and its treatment involves surgical resection, radiotherapy and chemotherapy with temozolamide, a protocol that promotes palliative improvement, increasing patient survival for up to 15 months after diagnosis. The present line of investigation could result in an effective contribution to the treatment of glioblastomas. (AU)