Published 6 issues per year
ISSN Print: 1040-8401
ISSN Online: 2162-6472
Indexed in
Cellular Mucins: Targets for Immunotherapy
ABSTRACT
Mucins are attracting great interest as potential targets for immunotherapy in the development of vaccines for cancers expressing Mucinl (MUC1) (e.g., breast, pancreas, ovary, and others) as there is (1) a 10-fold increase in the amount in adenocarcinomas; (2) an alteration in expression where they become ubiquitous, and (3) due to altered glycosylation, new epitopes appear on the cell surface that are absent in normal tissues. These new epitopes can be carbohydrate; others are peptide in nature. The cloning of the cDNAs from mucins, particularly MUC1, has led to rapid advances being made, and it is clear that a highly immunogenic peptide exists within the variable number of tandem repeats (VNTR) found in all mucins. This peptide is immunogenic in mice, giving rise to strong antibody production, and most monoclonal antibodies made to breast cancer, which react with the protein core, react with the peptide APDTR. It is now also clear that humans with breast cancer have, in their draining lymph nodes, precursors of cytotoxic T cells that can be stimulated in vitro to react against breast cancer and indeed against the APDTR or a closely related peptide − shown from antibody-blocking studies. These CTLs are unique in that they are non-MHC restricted. The identification of suitable targets, coupled with the known immunogenicity of both the peptide and neo-carbohydrate epitopes, has led to the development of several different programs to immunize humans against breast cancer using either synthetic carbohydrates or peptides conjugated with adjuvants, and clinical trials are now in progress to evaluate their immunogenicity and anti-cancer effects.
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Barriga Vanessa, Kuol Nyanbol, Nurgali Kulmira, Apostolopoulos Vasso, The Complex Interaction between the Tumor Micro-Environment and Immune Checkpoints in Breast Cancer, Cancers, 11, 8, 2019. Crossref
-
Fini M. Elizabeth, Jeong Shinwu, Gong Haiyan, Martinez-Carrasco Rafael, Laver Nora M.V., Hijikata Minako, Keicho Naoto, Argüeso Pablo, Membrane-associated mucins of the ocular surface: New genes, new protein functions and new biological roles in human and mouse, Progress in Retinal and Eye Research, 75, 2020. Crossref
-
Reily Colin, Stewart Tyler J., Renfrow Matthew B., Novak Jan, Glycosylation in health and disease, Nature Reviews Nephrology, 15, 6, 2019. Crossref
-
Jonckheere Nicolas, Vincent Audrey, Neve Bernadette, Van Seuningen Isabelle, Mucin expression, epigenetic regulation and patient survival: A toolkit of prognostic biomarkers in epithelial cancers, Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1876, 1, 2021. Crossref
-
Berriel Edgardo, Freire Teresa, Chiale Carolina, Rodríguez Ernesto, Morón Gabriel, Fernández-Graña Gabriel, Crispo Martina, Berois Nora, Osinaga Eduardo, Human hydatid cyst fluid-induced therapeutic anti-cancer immune responses via NK1.1+ cell activation in mice, Cancer Immunology, Immunotherapy, 70, 12, 2021. Crossref
-
Vafaei Rana, Samadi Mitra, Hosseinzadeh Aysooda, Barzaman Khadijeh, Esmailinejad MohammadReza, Khaki Zohreh, Farahmand Leila, Comparison of mucin-1 in human breast cancer and canine mammary gland tumor: a review study, Cancer Cell International, 22, 1, 2022. Crossref
-
Lath Amit, Santal Anita Rani, Kaur Nameet, Kumari Poonam, Singh Nater Pal, Anti-cancer peptides: their current trends in the development of peptide-based therapy and anti-tumor drugs, Biotechnology and Genetic Engineering Reviews, 2022. Crossref
-
Panasiuk Mirosława, Zimmer Karolina, Czarnota Anna, Narajczyk Magdalena, Peszyńska-Sularz Grażyna, Chraniuk Milena, Hovhannisyan Lilit, Żołędowska Sabina, Nidzworski Dawid, Żaczek Anna J., Gromadzka Beata, Chimeric virus-like particles presenting tumour-associated MUC1 epitope result in high titers of specific IgG antibodies in the presence of squalene oil-in-water adjuvant: towards safe cancer immunotherapy, Journal of Nanobiotechnology, 20, 1, 2022. Crossref
-
Lumibao Jan C., Tremblay Jacob R., Hsu Jasper, Engle Dannielle D., Altered glycosylation in pancreatic cancer and beyond, Journal of Experimental Medicine, 219, 6, 2022. Crossref
-
Brockhausen Inka, Melamed Jacob, Mucins as anti-cancer targets: perspectives of the glycobiologist, Glycoconjugate Journal, 38, 4, 2021. Crossref
-
Pollini Tommaso, Adsay Volcan, Capurso Gabriele, Dal Molin Marco, Esposito Irene, Hruban Ralph, Luchini Claudio, Maggino Laura, Matthaei Hanno, Marchegiani Giovanni, Scarpa Aldo, Wood Laura D, Bassi Claudio, Salvia Roberto, Mino-Kenudson Mari, Maker Ajay V, The tumour immune microenvironment and microbiome of pancreatic intraductal papillary mucinous neoplasms, The Lancet Gastroenterology & Hepatology, 2022. Crossref
-
Chavda Vivek P., Solanki Hetvi K., Davidson Majid, Apostolopoulos Vasso, Bojarska Joanna, Peptide-Drug Conjugates: A New Hope for Cancer Management, Molecules, 27, 21, 2022. Crossref