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Vaccine Detail
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MUC1-VNTR1 Peptides with Asn Substitutions at O-Glycosylation Sites: T3N, T10,18N (PD Context) and T3,11,16N, S2,T3,11,S12,T16N (GS Context) Variants |
| Vaccine Information |
- Vaccine Name: MUC1-VNTR1 Peptides with Asn Substitutions at O-Glycosylation Sites: T3N, T10,18N (PD Context) and T3,11,16N, S2,T3,11,S12,T16N (GS Context) Variants
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Peptide vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 VNTR (PDTRPAPGSTAPPAHGVTSA); MUC1 VNTR (GSTAPPAHGVTSAPDTRPAP) (Wright et al., 2010)
- Immunization Route: Ex vivo
- Description: A synthetic MUC1 variable number tandem repeat (VNTR1) peptide with asparagine (N) substitutions at O-linked glycosylation sites (threonine and/or serine residues) tested ex vivo using human PBMC from three breast adenocarcinoma patients against MCF-7 target cells. Peptides were evaluated in two sequence contexts (PD: PDTRPAPGSTAPPAHGVTSA; GS: GSTAPPAHGVTSAPDTRPAP) with substitutions ranging from single (T3N) to full replacement of all five glycosylation sites (S2,T3,11,S12,T16N). Stimulation of PBMC on days 0 and 7 with 1μg/mL peptide generated MUC1-specific CTL achieving 23–58% specific lysis of MCF-7 cells at 2.5–10:1 E:T ratios, with lysis slope increasing with E:T ratio for specific but not nonspecific targets. Tumor-selective lysis was 1.5- to 8-fold greater than nonspecific NK (K562) and LAK (Raji) targets with minimal NK/LAK activity. T3N exceeded IL-2 alone (13%) and unrelated gp120 peptide (14%) in ADC-1. T10,18N was equivalent to T3N across two donors. T3,11,16N was equivalent to T3N and T10,18N, and full substitution of all five sites (S2,T3,11,S12,T16N) was equivalent to one, two, or three substitutions, demonstrating that increasing substitutions from one to five did not inhibit CTL generation. Native GS produced markedly higher IFN-γ (439 pg/mL) compared to N-substituted peptides (20–117 pg/mL), with variable GM-CSF and TNF-α between donors. No IL-10 was detected with any N-substituted peptide, whereas native GS induced IL-10 rising from 11 to 30 pg/mL by day 8 (Wright et al., 2010).
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