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Dendritic cells targeted CEA tumor antigen through DEC205 in combination with oncolytic reovirus stimulate strong immune response in colorectal cancer model
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DOI：10.1016/j.cellimm.2026.105074.png)
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Abstract
En 中文
Background: Colorectal cancer is one of the most common cancers worldwide. Current treatments, including surgery, chemotherapy, and radiotherapy, have limitations due to their non-specific action, drug resistance, and inability to induce memory immune responses. The use of combination therapies for effective treatments appears to be more effective. In this study, the single and combined anti-tumor effects of immunotherapy targeting the CEA tumor antigen to dendritic cells and virotherapy with Reovirus were investigated in a mouse colorectal cancer model. Method: A recombinant adenovirus expressing the CEA gene fused to DEC205 was constructed to target dendritic cells (DCs). The single and combined effects of immunotherapy and virotherapy together with PD1/PDL1 inhibitor, lenalidomide, and CEA CT26 necrotic cells as adjuvants in the treatment of colorectal tumor models, were evaluated by assessing tumor growth, histological changes, and immune responses. The prophylactic effects of CEA immunization were also investigated. Results: Under pre-treatment conditions, CEA-targeted DCs, along with all three adjuvants, significantly reduced tumor growth (p-value<0.05) and enhanced cellular immune responses compared to the untreated group. Immunotherapy alone and in combination with virotherapy in tumor-bearing mice produced a stronger antitumor effect when injected with each of the three adjuvants compared to the untreated group. Conclusion: CEA-targeted immunotherapy and immune-virotherapy induced potent antitumor immune responses. Considering all measured parameters, there was not enough evidence to support the superiority of any single adjuvant; however, lenalidomide in combination therapy enhanced specific immune and antitumor effects. All the combination protocols used in this study were able to induce a strong antitumor immunity, and could be further optimized with additional adjunctive therapies for complete tumor remission.
Keywords:
Adjuvant
Dendritic cell
DEC205
Immunotherapy
Lenalidomide
Oncolytic reovirus
Prophylaxis
PD1-PDL1 inhibitor
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