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Vaccine Detail
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Site-Specifically Conjugated CRM197-MUC1 APDTRP Glycopeptide Vaccine with S-Glycosidic Tn and (4S)-4-Fluoro-L-Proline |
| Vaccine Information |
- Vaccine Name: Site-Specifically Conjugated CRM197-MUC1 APDTRP Glycopeptide Vaccine with S-Glycosidic Tn and (4S)-4-Fluoro-L-Proline
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Conjugate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 (Guerreiro et al., 2024)
- Immunization Route: subcutaneous injection
- Description: A chemically defined glycoconjugate vaccine consisting of a synthetic non-natural MUC1 glycopeptide site-specifically conjugated to CRM197 carrier protein via disulfide re-bridging at Cys186-Cys201. The glycopeptide antigen contains the immunogenic APDTRP epitope with two non-natural modifications: (4S)-4-fluoro-L-proline and S-?-D-GalNAc (S-glycosidic Tn antigen), designed for enhanced immunogenicity and enzymatic resistance. Site-specific conjugation produces a homogeneous 1:1 conjugate, eliminating batch-to-batch variability while maintaining CRM197 structural integrity. Vaccination elicits a robust Th1-type immune response with predominantly IgG2a/IgG2b antibodies, elevated IL-2, IFN-?, and TNF-?, and low IL-4, IL-10, and IL-13. Generated antibodies selectively recognize tumor-associated MUC1 on human cancer cells (T47D) and activate cytotoxic T-lymphocytes with ~20% tumor cell killing activity. In murine colon adenocarcinoma (MC38-MUC1) and pancreatic cancer (Panc02-MUC1) models, prophylactic vaccination reduced tumor volume by ~55% with complete prevention in 1/5 mice. Therapeutic vaccination achieved ~40-75% tumor reduction and 25-40% survival. Combined with anti-PD-1 checkpoint inhibitor, efficacy improved to ~70-84% tumor reduction, >20-80% survival, and one complete regression. MUC1 antigen, a membrane-bound glycoprotein expressed by glandular and ductal epithelial cells, is overexpressed in aberrant or truncated glycosylated forms in various cancers including breast, colon, pancreatic, and ovarian cancers (Guerreiro et al., 2024).
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| References |
Guerreiro et al., 2024: Guerreiro A, Compañón I, Lazaris FS, Labão-Almeida C, Oroz P, Ghirardello M, Marques MC, Corzana F, Bernardes GJL. Non-Natural MUC1 Glycopeptide Homogeneous Cancer Vaccine with Enhanced Immunogenicity and Therapeutic Activity. Angewandte Chemie (International ed. in English). 2024; 63(49); e202411009. [PubMed: 39275921].
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