|
|
Vaccine Detail
|
DC Vaccine Transduced with Recombinant Ad5 with F35 Fiber Modification Encoding MUC1 cDNA (7VNTR) (rAd5F35-MUC1) |
| Vaccine Information |
- Vaccine Name: DC Vaccine Transduced with Recombinant Ad5 with F35 Fiber Modification Encoding MUC1 cDNA (7VNTR) (rAd5F35-MUC1)
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Dendritic cell vaccine
- Status: Research
- Host Species for Licensed Use: Human
- Antigen: MUC1 (van Leeuwen et al., 2006)
- Immunization Route: Intramuscular injection (i.m.)
- Description: A dendritic cell-based vaccine using fiber-modified recombinant adenovirus serotype 5 with serotype 35 fiber chimera (rAd5F35) to transduce human monocyte-derived dendritic cells with full-length MUC1 containing 7 tandem repeats. Fiber modification enables efficient DC transduction (≥93%, ≥60% viability, 3 days). High-level MUC1 expression (≥500-1000 vp/cell) generates tumor-associated MUC1 glycoforms (Tn, T, sialyl-T; STn negative) on DC surface—the first demonstration of MUC1-transgenic DCs expressing cancer-associated glycoforms without glycosylation inhibitors. Transduced DCs maintain normal maturation with marked upregulation of HLA-DR, CD80, CD86, CD40, CD83; preserve naïve T-cell stimulation; and show 500-fold increased IL-12 production favorable for Th1/cytotoxic responses. Surface sialyl-T MUC1 does not shed or impair DC function, contrasting with recombinant ST-MUC1 studies. Tumor-associated MUC1 glycoforms may enhance antigen presentation through MHC class II-restricted presentation, direct T-cell recognition via MHC-unrestricted receptors, and B-cell activation. These glycoforms may bypass central tolerance as thymic medullary epithelial cells express fully glycosylated MUC1, not truncated forms. MUC1, a membrane-bound glycoprotein expressed by glandular and ductal epithelial cells, is overexpressed in aberrant or deglycosylated form in cancers including breast, pancreatic, and other carcinomas. This preclinical system provides basis for clinical dendritic cell vaccines targeting MUC1-expressing tumors (van Leeuwen et al., 2006).
|
| Host Response |
|
|
| References |
van Leeuwen et al., 2006: van Leeuwen EB, Cloosen S, Senden-Gijsbers BL, Agervig Tarp M, Mandel U, Clausen H, Havenga MJ, Duffour MT, García-Vallejo JJ, Germeraad WT, Bos GM. Expression of aberrantly glycosylated tumor mucin-1 on human DC after transduction with a fiber-modified adenoviral vector. Cytotherapy. 2006; 8(1); 24-35. [PubMed: 16627342].
|
|
