{
  "abstract": "BackgroundColorectal 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.MethodsWe 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).ResultsImmunodominant epitopes (CD66c76–92 and CD66c141–156) 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.ConclusionCD40-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.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "name": "Dhanapal Yogananthan"
    },
    {
      "name": "Ashok Raj Kattur Venkatachalam"
    },
    {
      "name": "Ramanathan Muthiah"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5vm552a8tqzs3.bib",
  "cited_by": 0,
  "doi": "10.3389/fonc.2026.1848758",
  "fulltext_url": null,
  "id": "5vm552a8tqzs3",
  "issns": [
    "2234-943X"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1848758",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "feed-journal",
      "medicine/oncology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-09",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/5vm552a8tqzs3.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T06:20:10Z",
      "native_id": "10.3389/fonc.2026.1848758",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1848758"
    },
    {
      "first_seen": "2026-11-09T12:23:35Z",
      "native_id": "10.3389/fonc.2026.1848758",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1848758/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "feed-journal:medicine/oncology",
      "subfield": "oncology"
    }
  ],
  "title": "CD66c-targeted CD40B adaptive transfer to enhance cytotoxic T cell responses in colorectal cancer",
  "title_text": "CD66c-targeted CD40B adaptive transfer to enhance cytotoxic T cell responses in colorectal cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:23:35Z",
  "url": "https://research.draconitic.com/paper/5vm552a8tqzs3",
  "venue": "Frontiers in Oncology",
  "versions": []
}