CD66c-targeted CD40B adaptive transfer to enhance cytotoxic T cell responses in colorectal cancer
Year: 2026
Type: article
Abstract: Background Colorectal cancer (CRC), particularly microsatellite-stable (MSS) CRC, shows a limited response to immune checkpoint inhibitors (ICIs). Novel strategies are needed to enhance antigen-specific T cell immunity. CD66c (CEACAM6) is a tumour-associated antigen overexpressed in CRC and involved in immune evasion. CD40-activated B cells (CD40B) can function as effective antigen-presenting cells (APCs) in adoptive immunotherapy. Methods We screened a CD66c-derived peptide library using IFN-γ ELISpot assays in peripheral blood mononuclear cells (PBMCs) from patients with CRC and healthy controls to identify immunodominant epitopes. We isolated antigen-specific B cells, activated them with CD40 ligand, and characterised them by flow cytometry. Their capacity to induce T-cell activation was assessed in-vitro . In-vivo efficacy was evaluated in CT-26 syngeneic murine models following adoptive transfer of peptide-loaded CD40B cells, with or without anti–PD-1 therapy (pembrolizumab). Results Immunodominant epitopes (CD66c 76–92 and CD66c 141–156 ) elicited robust IFN-γ responses in vitro . CD40B cells showed enhanced expression of co-stimulatory molecules (CD80/CD86) and MHC class I/II. In vitro , CD66c-loaded CD40B induced significant CD4 + and CD8 + T-cell proliferation and activation. In vivo , adoptive transfer of CD66c-loaded CD40B cells augmented antigen-specific CD8 + T-cell responses, tumour-specific cytolysis of up to ~96% under optimised conditions, and tumour growth inhibition. Combination therapy with pembrolizumab showed synergistic effects, including enhanced intratumoral CD8 + T-cell infiltration, increased CD66c-specific IgG1 levels, and improved survival. Conclusion CD40-activated B cells targeting CD66c peptides may represent a promising preclinical platform for inducing antigen-specific cytotoxic T cell responses in CRC. This approach may improve responses to checkpoint blockade in preclinical settings; however, further validation in humanised models and clinical systems is required to establish its translational applicability.
Source: Frontiers in Oncology
Institutions: PSG College of Pharmacy, PSG College of Arts & Science
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7225658132