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Vaccine Detail
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MUC1-maltose-binding protein (MBP)/BCG vaccine |
| Vaccine Information |
- Vaccine Name: MUC1-maltose-binding protein (MBP)/BCG vaccine
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Subunit vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: Maltose binding protein (MBP); 7 MUC1 VNTRs, 140aa; SAPDTRPAPGSTAPPAHGVT (Fang et al., 2014), GVTSAPDTRPAPGSTAPPAH (Hu et al., 2016)
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Adjuvant:
BCG (Fang et al., 2014; Hu et al., 2016)
- Immunization Route: subcutaneous injection
- Description: A recombinant fusion protein vaccine consisting of seven human MUC1 VNTR tandem repeats (140 amino acids) fused to Escherichia coli maltose-binding protein (MBP), yielding a 62 kDa fusion protein, combined with BCG as adjuvant. In C57BL/6 mice (Fang et al., 2014), MUC1-MBP/BCG induced the highest Th1-associated IgG2c titers and lowest IgG1 levels among all tested formulations, with significantly elevated IFN-γ from MUC1-restimulated splenocytes vs. MUC1/BCG and MUC1-MBP alone, and no changes in IL-4 or TNF-α. Only MUC1-MBP/BCG elicited MUC1-specific CTL killing of B16-MUC1 melanoma cells at E/T ratios of 50:1 and 25:1, with no cytotoxicity against B16-neo cells, and synergistically higher NK cytotoxicity against YAC-1 targets at 100:1 and 50:1. In prophylactic challenge, MUC1-MBP/BCG reduced B16-MUC1 melanoma tumor weight by 61% (1.51±0.67 g vs. 3.87±1.01 g; P<0.05) with sustained inhibition through day 21; therapeutic immunization produced similar MUC1-specific inhibition but with reduced magnitude (Fang et al., 2014). In pre-clinical safety studies across mice, rats, and cynomolgus monkeys (Hu et al., 2016), the vaccine was well tolerated with no organ toxicity; BCG-attributable injection site reactions and transient elevations in WBC, neutrophils, monocytes, and spleen weight resolved during recovery. In rats, 100% seroconversion was achieved by day 7 with peak IgG titers of 1:6400 at day 14, persisting in 9/10 high-dose animals after four-week recovery, with significantly elevated IFN-γ at four weeks post-final immunization and no changes in IL-4 or TNF-α (Hu et al., 2016). In cynomolgus monkeys, MUC1-specific IgG peaked at 1:3200 on day 29 with IgG1 as the dominant subclass, declining to 26% of peak titers eight weeks post-immunization (Hu et al., 2016).
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| Host Response |
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| References |
Fang et al., 2014: Fang F, Ma J, Ni W, Wang F, Sun X, Li Y, Li Q, Xie F, Wang J, Zhai R, Liu Z, Gao S, Tai G. MUC1 and maltose‑binding protein recombinant fusion protein combined with Bacillus Calmette‑Guerin induces MUC1‑specific and nonspecific anti‑tumor immunity in mice. Molecular medicine reports. 2014; 10(2); 1056-1064. [PubMed: 24912810].
Hu et al., 2016: Hu B, Wang J, Guo Y, Chen T, Ni W, Yuan H, Zhang N, Xie F, Tai G. Pre-clinical toxicity and immunogenicity evaluation of a MUC1-MBP/BCG anti-tumor vaccine. International immunopharmacology. 2016; 33; 108-118. [PubMed: 26896668].
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