Synthetic Antitumor Vaccines Containing MUC1 Glycopeptides with Two Immunodominant Domains—Induction of a Strong Immune Response against Breast Tumor Tissues

Abstract

A shot in the arm for cancer treatment: two MUC1 tetanus toxoid vaccines were synthesized and induced a strong immune response in mice. The antibodies elicited by the vaccines show a high selectivity for the tumor cells in mammary carcinoma tissues and also distinguish between tumor tissues at different stages.

L-BLP25 Vaccine plus Letrozole Induces a TH1 Immune Response and Has Additive Antitumor Activity in MUC1-Expressing Mammary Tumors in Mice

“…Overall expression of MUC1 increases on cancer cells and it is underglycosylated revealing variable number of tandem repeat regions (VNTR) on a peptide backbone. T cells specific for antigenic epitopes of MUC1 that bind to HLA class I molecules have been identified and isolated from the blood and bone marrow of patients with breast cancer and myeloma, making MUC1 a potential target for a cellular immune response (4)(5)(6)(7)(8)(9)(10). In addition, the immunodominant peptides from the VNTR region are recognized by CTLs that are thought to destroy tumor cells expressing the underglycosylated form of MUC1 (11)(12)(13)(14).…”

Convergent Solid-Phase Synthesis of Macromolecular MUC1 Models Truly Mimicking Serum Glycoprotein Biomarkers of Interstitial Lung Diseases

“…Merit of this strategy is clear because the repertories of synthetic glycoproteins with highly complex glycans can be expanded when combined complementarily with the powerful synthetic methods directing macromolecular peptides and glycopeptides. [32][33][34][35][36] Considering accumulated evidences that epimerization of Asp and Ser residues are often detected in proteins implicated to some neurodegenerative diseases, 37,38 it is of emerging importance to pay particular attention to the effects of chiral purity of synthetic peptides/glycopeptides on the focused biological activities to be tested. The present results may motivate us to challenge the synthesis of various mucin domains towards insights into the significance of the posttranslational glycosylations [10][11][12]39,40 and the discovery of the disease-relevant glycopeptidic epitopes of the antibodies/vaccines against cancers, neurodegenerative diseases, and inflammatory diseases.…”

Synthetic Vaccines against Cancers

“…In another report, new synthetic MUC1-based vaccines containing two immunodominant domains have been elaborated [16]. As nuclear magnetic resonance (NMR) spectroscopic analyses revealed, the glycan side chains in the Ser-Thr-Ala-Pro-Pro-Ala sequence strongly influence the peptide conformation and tumor selectivity, and the authors decided to incorporate the STn antigen at the serine or the threonine at positions [17] and [18] (3) (Fig.…”

“…This result prompted the authors to design new structures containing combinations of human leukocyte antigen (HLA)-restricted T-helper epitopes, i.e. PV, TTox, or universal Pan DR (PADRE) with trimeric Tn antigens (16) linked to serine, threonine [46], or homoserine [47] (Fig. 14.12).…”