Principal Investigator:
Bruno Sarmento
Leader Institution:
CESPU
Funding entity:
CESPU
Budget:
4.500 euros
Period covered:
2023-2025
Abstract:
| Rectal cancer (RC) is one of the most incident cancers worldwide, accounting for more than one-third of colorectal cancers. Current RC chemotherapy regimens are based on 5-fluorouracil (5-FU), but their low selectivity and limited bioavailability at the tumor site restrict their efficacy. CD8+ T cells play a crucial role in tumor immune surveillance. In RC, increased CD8+ T-cell infiltration into the tumor microenvironment (TME) is associated with better outcomes. This project proposes a novel therapeutic combination based on the co-administration of 5-FU nanoparticles (NPs) targeting RC cells and NPs carrying recombinant CCL2 (rCCL2) with radiotherapy to eliminate RC cells and stimulate an immunogenic tumor microenvironment, improving RC patient’s outcome. Solid lipid nanoparticles (SLN) conjugation with an anti-carcinoembryonic antigen (CEA) scFV will bestow NPs with RC targetability. Functionalized NPs will be characterized, and their biological impact as a single therapy or in combination with radiotherapy assessed in three-dimensional (3D) tumor spheroids based on RC cells, human intestinal fibroblasts (HIF), macrophages, and CD8+ T cells, to better mimic the RC environment. |
Program:
GI2-CESPU-2023