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Vaccine Detail
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Recombinant Vaccinia Virus Encoding Human MUC1 and IL-2 (TG1031) |
| Vaccine Information |
- Vaccine Name: Recombinant Vaccinia Virus Encoding Human MUC1 and IL-2 (TG1031)
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Recombinant vector vaccine
- Status: Clinical trial
- Host Species for Licensed Use: Human
- Antigen: 5 MUC1 VNTRs (Scholl et al., 2000)
- Immunization Route: Intramuscular injection (i.m.)
- Description: A live recombinant vaccinia virus (Copenhagen strain) encoding human MUC1 cDNA with five tandem-repeated VNTR sequences and human IL-2 under the p7.5 promoter, attenuated through thymidine kinase inactivation. MUC1 is overexpressed and aberrantly glycosylated in most breast tumors; co-expressed IL-2 was designed to overcome MUC1-mediated T-cell inhibition and shift responses toward cellular immunity. Administered intramuscularly at three dose levels (5×10⁵, 5×10⁶, and 5×10⁷ PFU) with optional boost in nine patients with advanced inoperable breast cancer chest wall recurrences. No significant adverse events occurred and all viral cultures and PCR assays were negative. Five patients showed increased anti-vaccinia antibody titers; no MUC1-specific antibody responses were detected. Cellular immune responses occurred in 3/9 patients: patient 2 showed MUC1-specific CTLs at day 14 (survived 30+ months); patient 4 showed vaccinia proliferative response (SI 6) and transient MUC1-specific CTLs at day 14, with highest CD4⁺ counts and lowest M-CSF (232 pg/mL), surviving 20 months; patient 5 showed MUC1-specific PBMC stimulation indices of 7 and 14 after first and boost injections, with CEA decreasing from 158 to 115 ng/mL and chest wall lesions stable for 10 weeks. MUC1 peptide stimulation induced TNF-α (6/9), IL-6 (5/9), and IFN-γ (patient 9, day 23). Minor cervical lymph node regression occurred in patient 1. Tumor deposit inflammation in all patients days 2–5 coincided with transient VEGF and TGF-β decreases at days 2–4. Immunohistochemistry revealed increased CD45RO⁺ T memory cells, transient CD1a⁺ dendritic cells, and HLA class II expression on tumor-infiltrating cells in five patients. Favorable responders had CD4⁺>400, low M-CSF, TGF-β1, IL-6, and CRP; high M-CSF (>1,245 pg/mL) and elevated soluble IL-2R (120–180 pmol/L) correlated with poor immune response. Eight of nine patients died of progressive disease (Scholl et al., 2000).
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| Host Response |
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| References |
Scholl et al., 2000: Scholl SM, Balloul JM, Le Goc G, Bizouarne N, Schatz C, Kieny MP, von Mensdorff-Pouilly S, Vincent-Salomon A, Deneux L, Tartour E, Fridman W, Pouillart P, Acres B. Recombinant vaccinia virus encoding human MUC1 and IL2 as immunotherapy in patients with breast cancer. Journal of immunotherapy (Hagerstown, Md. : 1997). 2000; 23(5); 570-580. [PubMed: 11001550].
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