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Vaccine Detail
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pcDNA3.1-MUC1 plasmid vaccine |
| Vaccine Information |
- Vaccine Name: pcDNA3.1-MUC1 plasmid vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: DNA vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 extracellular domain (Wang et al., 2024)
- Immunization Route: Intramuscular injection (i.m.)
- Description: A plasmid DNA vaccine encoding the extracellular domain of human MUC1, cloned into the pcDNA3.1(−) expression vector and delivered by intramuscular injection with electroporation (electric square porator) into pre-anaesthetized (0.5% procaine) posterior tibialis muscle at 20 µg per dose, with a booster at 2 weeks. It was tested as monotherapy and in combination with anti-PD1 antibody (clone 29F.1A12, 200 µg/mouse i.v., days 7, 10, 14) in BALB/c mice bearing subcutaneous CT26/MUC1 colon carcinoma tumours. PD1 antibody monotherapy produced no tumour growth reduction, no survival improvement, no change in PD1 expression on intratumoural CD4+ or CD8+ T cells, no change in IFN-γ production, and no change in the CD8+/CD4+ ratio, establishing this model as fully PD1 antibody-resistant. A reduction in MDSCs (CD11b+Gr-1+) was observed (p<0.05) but had no impact on tumour growth kinetics. MUC1 DNA vaccine monotherapy produced no body weight change relative to wild-type controls. Splenic IFN-γ+CD8+ T cells were increased at 16.20% vs. 10.83% WT and GzmB+CD8+ T cells at 11.02% vs. 3.26% WT, while IFN-γ+CD4+ T cells increased to 5.20% vs. 1.55% vector and GzmB+CD4+ T cells remained unchanged (2.97% vs. 2.23%). MUC1-specific CD8+ T cell proliferation reached 41.17% vs. 0.29% (p<0.01) and LDH cytotoxicity was significantly enhanced at 10:1, 50:1, and 100:1 E:T ratios (p<0.05). Combination therapy inhibited tumour growth versus all monotherapy arms (p<0.05) and prolonged survival (p<0.001). Intratumoural IFN-γ+CD8+ T cells reached 45.33% vs. 22.7%, IFN-γ+CD4+ T cells 23.8% vs. 8.91%, GzmB+CD8+ T cells 49.98% vs. 39.22%, while GzmB+CD4+ T cells remained unchanged. MDSCs were reduced to 5.1% vs. 40.1% (p<0.01) and Treg cells to 8.61% vs. 21.21% (p<0.05), with the CD8+/CD4+ ratio significantly elevated (p<0.05). Absolute CD8+ T cells increased to 6.12×10⁵/g vs. 1.16×10⁵/g (p<0.05), CD4+ T cells increased (p<0.01), and MDSCs per gram were reduced (p<0.05). Immunohistochemistry confirmed a CD8+ cell density of 612.33±44.51 vs. 215.66±17.81 cells/mm². CXCL13 mRNA and protein were significantly upregulated (p<0.05), and CXCR5+CD8+ T cells increased to 70.96% vs. 20.43% of infiltrating CD8+ T cells (p<0.05). CXCL13 blockade reduced CD8+ infiltration to 9.68% vs. 18.36% of CD45+ intratumoural cells and CXCR5+CD8+ T cells to 59.39% vs. 71.55%, attenuating combination therapy efficacy (p<0.05). CD8+ T cell depletion similarly attenuated combination therapy efficacy (p<0.05), confirming CD8+ T cells as the central effectors of the anti-tumour response (Wang et al., 2024).
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| Host Response |
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| References |
Wang et al., 2024: Wang X, Miao Y, Shen J, Li D, Deng X, Yang C, Ji Y, Dai Z, Ma Y. Unlocking PD-1 antibody resistance: The MUC1 DNA vaccine augments CD8(+) T cell infiltration and attenuates tumour suppression. Scandinavian journal of immunology. 2024; 99(5); e13356. [PubMed: 38605549].
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