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Vaccine Detail
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Ad5 Vector Signal-hMUC1/CD40L Extracellular Domain Vaccine |
| Vaccine Information |
- Vaccine Name: Ad5 Vector Signal-hMUC1/CD40L Extracellular Domain Vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Recombinant vector vaccine
- Status: Clinical trial
- Host Species for Licensed Use: Human
- Antigen: MUC1 VNTR (20aa) (Tan et al., 2022)
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Adjuvant:
CD40L (CD40 ligand extracellular domain) (Tan et al., 2022)
- Immunization Route: subcutaneous injection
- Description: A recombinant Adenovirus 5 (Ad5) viral vector vaccine encoding a fusion protein of human MUC1 (20aa tandem repeat) and the extracellular domain of CD40 ligand (CD40L) under a CMV promoter with a human growth hormone signal peptide (45,000 nt plasmid). Administered subcutaneously in a first-in-human Phase I dose-escalation trial (NCT02140996) across single and multiple injection cohorts (up to 5 injections) at doses ranging from 1×10⁹ to 1×10¹¹ viral particles in 21 patients with locally recurrent or metastatic MUC1-overexpressing adenocarcinomas (breast, ovary, and lung [n=1, 5%]). MUC1 is a tumour-associated antigen ubiquitously overexpressed and hypoglycosylated in epithelial adenocarcinomas, while CD40L enhances dendritic cell licensing, promotes Th1 responses, and may directly inhibit tumour growth. The vaccine demonstrated safety and tolerability with no dose-limiting toxicities; all drug-related adverse events were Grade 1–2, most commonly injection site reactions (71%). MUC1-specific IFNγ ELISpot responses were significantly induced; 15/21 patients had pre-existing anti-adenovirus seropositivity. Mass cytometry (CyTOF) revealed significant post-vaccination increases in IFNγ+/GZMB+/TNFα+ cytotoxic CD8+ T cells (p=0.0387) and CD14+ monocytes (p=0.0459), with CD1c+ dendritic cells also increased by unsupervised analysis. Network analysis showed increased positive immune correlations (260→281), decreased negative correlations (101→76), and reduced modularity (0.118→0.104), indicating broader immune integration post-vaccination. In stable disease patients (n=6), vaccination significantly increased GZMB+/TIGIT+ cytotoxic CD8+ T cells (p=0.0087) and CXCR5+ B cells (p=0.0411). Of 17 patients with measurable disease, 10 (48%) achieved stable disease and 7 (33%) had progressive disease with no confirmed partial or complete responses (Tan et al., 2022).
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| Host Response |
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| References |
Tan et al., 2022: Tan TJ, Ang WXG, Wang WW, Chong HS, Tan SH, Cheong R, Chia JW, Syn NL, Shuen WH, Ba R, Kaliaperumal N, Au B, Hopkins R, Li X, Tan AC, Seet AOL, Connolly JE, Arkachaisri T, Chew V, Lajam ABM, Guo D, Chew MZW, Wasser M, Kumar P, Albani S, Toh HC. A phase I study of an adenoviral vector delivering a MUC1/CD40-ligand fusion protein in patients with advanced adenocarcinoma. Nature communications. 2022; 13(1); 6453. [PubMed: 36307410].
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