Context of MUC1 epitope: Immunogenicity

Quinlin, Imelda S.; Burnside, Janet S.; Dombrowski, K. E.; Phillips, Chris; Dolby, Nichol; Wright, Stephen E.

doi:10.3892/or.17.2.453

Cited by 13 publications

(25 citation statements)

References 8 publications

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“…The extracellular domain of MUC1 primarily consists of 25-125 various number tandem repeats (VNTR) of 20 amino acids and varies among individuals or directly derived tissues (4), which is the most immunogenic part of MUC1 and many T and B cell antigen recognition sites generated to date almost exclusively recognize epitopes in that immunogenic region (23)(24)(25). Thus, MUC1-VNTR sequences may be expected to induce host immune specific CTL responses and as a possible target treatment approach for MM.…”

Section: Discussionmentioning

confidence: 99%

A unique MUC1-2-VNTR DNA vaccine suppresses tumor growth and prolongs survival in a murine multiple myeloma model

et al. 2012

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Abstract. Multiple myeloma (MM) is a clonal B-cell malignancy charactered by the aberrant proliferation of malignant plasma cells in the bone marrow. MM is still an incurable malignancy. In this regard, novel treatments are urgently required. MUC1 (mucin 1), a type І transmembrane protein, is overexpressed and aberrantly glycosylated in many carcinomas particularly in MM resulting in an antigenically distinct molecule and may be a potential target for specific immunotherapy. In this study, we first designed a unique DNA vaccine, termed MUC1-2-VNTR (various number tandem repeats) to investigate whether the vaccine could specifically suppress tumor growth in a murine multiple myloma model. Our results showed that the constructed DNA vaccine pcDNA3.1-VNTR elicited both humoral and cellular tumor-specific immune responses in the MM mouse model leading to delay in tumor growth and prolonged survival of the mice. Consequently, our study indicates that this DNA vaccine shows promise to be used as a novel strategy for the treatment of MM.

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Section: Discussionmentioning

confidence: 99%

A unique MUC1-2-VNTR DNA vaccine suppresses tumor growth and prolongs survival in a murine multiple myeloma model

et al. 2012

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“…The peptide with substitutions S2,T3,11,S12,T16N was similar to T3N, T10,18N, T3,11,16N and native GS context in generating both specific CTL (58, 54, 50, 52, and 53% lysis of MCF-7, respectively) (Figure 2A), and nonspecific NK cells (14,38,33,36, and 9% lysis of K562, respectively) ( Figure 2B) and LAK cells (24,34,25,32, and 21% lysis of Raji, respectively) ( Figure 2C). The native GS context generated less nonspecific NK cells (9% lysis of K562) ( Figure 2B) and LAK cells (21% lysis of Raji) ( Figure 2C).…”

Section: Immunogenicity Of Substituted Gs Context Muc1-vntr1-stimulatmentioning

confidence: 95%

“…After observing that the GS context was superior to the PD context in inducing cellular immunity, based on target cell lysis and cytokine production, 33 the remaining S and T to N substitutions were performed in the GS context. To determine if all three T to N substitutions affect the ability to generate CTL, the following experiments were performed with ADC-2′s cells.…”

Section: Immunogenicity Of Substituted Gs Context Muc1-vntr1-stimulatmentioning

confidence: 99%

Retention of immunogenicity produced by mucin1 peptides with glycosylation site substitutions

Wright

Quinlin

Dombrowski

et al. 2010

Immunopharmacology and Immunotoxicology

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Mucin1 (MUC1) with altered glycosylation behaves as an antigen unique to adenocarcinomas (ADCs). As a step toward DNA vaccines, the goal of this work was to determine whether MUC1 peptides substituted with an asparagine at O-linked glycosylation sites, might expose MUC1 peptide backbone to serve as immunogens to generate cytotoxic T lymphocytes (CTL) from peripheral blood mononuclear cells of patients with ADCs. Substitution of some or all tyrosine and serine residues by asparagine in MUC1 did not inhibit the generation of mucin-specific CTLs. This suggests that MUC1 tandem repeat altered sequences to prevent O-linked glycosylation may be useful as DNA vaccines with tumor specificity.

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“…Thus, ex vivo stimulated CTL adoptive therapy is a feasible approach. A translational research trial was designed to study in vitro and in vivo effects of ex vivo stimulated CTL with an optimized MUC1 context (Quinlin, 2007). After standard therapy, lymphocytes from subjects were collected, stimulated and expanded ex vivo for use as adoptive immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

Number of Treatment Cycles Influences Development of Cytotoxic T Cells in Metastatic Breast Cancer Patients – A Phase I/II Study

Wright

Quinlin

Phillips

et al. 2010

Immunological Investigations

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The influence of the number of apheresis-stimulation-infusion(s) cycles, and the time in culture before the infusion (one vs. two weeks), on the generation of tumor antigen-specific cytotoxic T-lymphocytes (CTL) was investigated in a phase I/II clinical adoptive immunotherapy trial. Two previously treated metastatic breast cancer patients with no evidence of disease, in complete remission (CR), were enrolled. Each apheretic peripheral blood mononuclear cell (PBMC) sample was stimulated twice with MUC-1 before infusion back into the patients. Killer T-cells responses against MUC-1-expressing MCF-7 (CTL), nonspecific natural killer (NK) and lymphokine-activated killer (LAK) target cell lines, as well as, cytokine production were measured before each infusion. Patients received 2 infusions per month for 4 months. There were no tumor recurrences or toxicity. CTL, NK and LAK cells, type 1 cytokine, gamma-interferon (G-INF), and CD4(+) and CD8(+) memory T-lymphocytes were initially generated, produced or induced, respectively, and then declined. The CTL, NK and LAK cells were only induced at the first infusion of the first month. Thus, maintaining PBMC in culture longer than the first infusion was of no benefit with regards to retaining functional killer T-cells. In conclusion, this study implies that one treatment is optimal.

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Context of MUC1 epitope: Immunogenicity

Cited by 13 publications

References 8 publications

A unique MUC1-2-VNTR DNA vaccine suppresses tumor growth and prolongs survival in a murine multiple myeloma model

A unique MUC1-2-VNTR DNA vaccine suppresses tumor growth and prolongs survival in a murine multiple myeloma model

Retention of immunogenicity produced by mucin1 peptides with glycosylation site substitutions

Number of Treatment Cycles Influences Development of Cytotoxic T Cells in Metastatic Breast Cancer Patients – A Phase I/II Study

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