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
Vani LakshminarayananSandra J Gendler

Abstract

It remains challenging to produce decisive vaccines against MUC1, a tumor-associated antigen widely expressed by pancreas, breast and other tumors. Employing clinically relevant mouse models, we ruled out such causes as irreversible T-cell tolerance, inadequate avidity, and failure of T-cells to recognize aberrantly glycosylated tumor MUC1. Instead, every tested MUC1 preparation, even non-glycosylated synthetic 9mer peptides, induced interferon gamma-producing CD4(+) and CD8(+) T-cells that recognized glycosylated variants including tumor-associated MUC1. Vaccination with synthetic peptides conferred protection as long as vaccination was repeated post tumor challenge. Failure to revaccinate post challenge was associated with down-regulated tumor MUC1 and MHC molecules. Surprisingly, direct admixture of MUC1-expressing tumor with MUC1-hyperimmune T-cells could not prevent tumor outgrowth or MUC1 immunoediting, whereas ex vivo activation of the hyperimmune T-cells prior to tumor admixture rendered them curative. Therefore, surrogate T-cell preactivation outside the tumor bed, either in culture or by repetitive vaccination, can overcome tumor escape.

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Citations

Jul 30, 2016·Vaccines·Md Kamal Hossain, Katherine A Wall
Mar 27, 2019·Cancers·Md Kamal Hossain, Katherine A Wall
Aug 2, 2017·Medicinal Research Reviews·Maryam Sadat NabaviniaKhalil Abnous
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Jul 15, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Md Kamal HossainKatherine A Wall
Mar 12, 2021·Glycoconjugate Journal·Inka Brockhausen, Jacob Melamed
Sep 12, 2020·Chemical Reviews·Wen-Hao Li, Yan-Mei Li

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Methods Mentioned

BETA
transgenic
glycosylation
flow cytometry
confocal microsopy
Assay

Software Mentioned

DIVA
Cosmc
Zeiss LSM image browser
FlowJo star

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