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Vaccine Detail
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MUC1 Rotating Tumor Lysate Vaccines (C57mg, KCM, EL4, B16) |
| Vaccine Information |
- Vaccine Name: MUC1 Rotating Tumor Lysate Vaccines (C57mg, KCM, EL4, B16)
- Target Pathogen: Cancer
- Target Disease: Cancer
- Type: Whole tumor lysate vaccine
- Status: Research
- Host Species for Licensed Use: Mouse
- Antigen: MUC1 (Lakshminarayanan et al., 2016)
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Adjuvant:
CpG 1826/IFA (Lakshminarayanan et al., 2016)
- Immunization Route: subcutaneous injection
- Description: A whole tumor cell lysate vaccine composed of rotating lysates from four MUC1-expressing tumor cell lines (C57mg, KCM, EL4, B16) representing diverse tissue origins (mammary, pancreatic, lymphoma, melanoma), adjuvanted with CpG 1826 oligonucleotide and Incomplete Freund's Adjuvant (IFA). Lysates were prepared by freeze-thaw cycles and contain full-length, naturally glycosylated MUC1 with tumor-associated glycoforms. The rotating vaccination strategy (1st: C57mg; 2nd: KCM; 3rd: EL4; 4th: C57mg) generates the most diverse T-cell repertoire, with increased CD4+ and CD8+ interferon-gamma producing responses recognizing all 19 tested MUC1 peptides from both tandem repeat and non-tandem repeat regions, including preferential CD4+ recognition of glycosylated epitopes (19% for SAP Tn-9mer vs 9% for non-glycosylated SAP 9mer). In prophylactic settings, vaccination achieved 40-50% B16.MUC1 tumor rejections with significantly delayed tumor growth in non-rejecting mice (p<0.001), and prolonged survival in Panc02.MUC1 and MC38.MUC1 challenges. Adoptive transfer of lysate-primed T-cells after ex vivo activation achieved 100% cures in Winn assays. However, MUC1.Tg mice demonstrated incomplete immunological memory upon rechallenge, with tumor outgrowth showing decreased MUC1 and MHC expression. MUC1 is a membrane-bound glycoprotein overexpressed in an aberrant or underglycosylated form in approximately 75% of lethal human cancers including breast, pancreatic, and ovarian cancers (Lakshminarayanan et al., 2016).
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| Host Response |
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| References |
Lakshminarayanan et al., 2016: Lakshminarayanan V, Supekar NT, Wei J, McCurry DB, Dueck AC, Kosiorek HE, Trivedi PP, Bradley JM, Madsen CS, Pathangey LB, Hoelzinger DB, Wolfert MA, Boons GJ, Cohen PA, Gendler SJ. MUC1 Vaccines, Comprised of Glycosylated or Non-Glycosylated Peptides or Tumor-Derived MUC1, Can Circumvent Immunoediting to Control Tumor Growth in MUC1 Transgenic Mice. PloS one. 2016; 11(1); e0145920. [PubMed: 26788922].
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