The immunogenicity of MUC1 peptides and fusion protein

Apostolopoulos, Vasso; Pietersz, Geoffrey A.; Xing, Pei‐Xiang; Lees, Catherine; Michael, M.; J, Bishop

doi:10.1016/0304-3835(94)03673-7

Cited by 33 publications

(20 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similarly in a therapy experiment, 3 injections with MFP was also inadequate in decreasing tumour burden in mice with established DA3-MUC1 tumours. These findings were unlike other studies with MFP, whereby mice immunised with MFP were totally protected against a challenge of MUC1 + 3T3 tumours [20,21] and the induction of a CD8 + cellular immune response caused the regression of established 15 day-old MUC1 + P815 tumours in DBA/2 mice [31]. In vitro and in vivo characterisation of DA3-MUC1 indicated that the tumour was weakly immunogenic because even though high surface levels of MUC1 were expressed (> 85%), there were low levels of all other cell surface molecules needed for T cell activation including MHC class I (< 6%), MHC class II, CD80, ICAM-2, CD28, LFA-2 and CTLA-4.…”

Section: T Cells From Mfp Immunised Mice Lyse Ifn-γ Treated Da3-muc1 contrasting

confidence: 56%

“…A MUC1-GST fusion protein containing 5 variable number of tandem repeat (VNTR) regions from the extracellular protein core of MUC1 [14] was produced in a bacterial expression system (pGEX-3X) and conjugated to oxidised mannan to form MFP as described previously [15][16][17][18][19][20][21][22][23]. BALB/c mice aged 6-10 weeks were given three intraperitoneal immunisations (on days 0, 7 and 14) with either MFP (containing 5μg of MUC1 fusion protein) or a control pH 9.0 phosphate buffer.…”

Section: Mice and Immunisationsmentioning

confidence: 99%

See 1 more Smart Citation

MUC1 immunotherapy against a metastatic mammary adenocarcinoma model: Importance of IFN-gamma

Lees¹,

Smorodinsky

Horn

et al. 2016

Prilozi

View full text Add to dashboard Cite

Immunotherapy using mucin 1 (MUC1) linked to oxidised mannan (MFP) was investigated in an aggressive MUC1 + metastatic tumour, DA3-MUC1 because, unlike many MUC1 + tumour models, DA3-MUC1 is not spontaneously rejected in mice making it an alternative model for immunotherapy studies. Further, DA3-MUC1 cells are resistant to lysis by anti-MUC1 cytotoxic T cells (CTLs). The inability of DA3-MUC1 tumours to be rejected in naïve mice as well as vaccination to MUC1 was attributed to a deficiency of expression of MHC class I molecules on the tumour cell surface. In vitro and in vivo analysis of subcutaneous tumours and lung metastases demonstrated that DA3-MUC1 tumour cells have a low expression (< 6%) of MHC class I which can be upregulated (> 90%) following culturing with IFN-γ. Results from flow cytometry analysis and immunoperoxidase staining indicated that the in vitro up-regulation of MHC class I could be maintained for up to seven days in vivo, without affecting the expression levels of MUC1 antigen. Interestingly, MUC1-specific CTL that lyse DA3-MUC1 targets in vitro were induced in MFP immunised mice but failed to protect mice from a DA3-MUC1 tumour challenge. These results highlight the importance of MHC class I molecules in the induction of anti-tumour immunity and the MFP immune response.

show abstract

Section: T Cells From Mfp Immunised Mice Lyse Ifn-γ Treated Da3-muc1 contrasting

confidence: 56%

Section: Mice and Immunisationsmentioning

confidence: 99%

MUC1 immunotherapy against a metastatic mammary adenocarcinoma model: Importance of IFN-gamma

Lees¹,

Smorodinsky

Horn

et al. 2016

Prilozi

View full text Add to dashboard Cite

show abstract

“…In addition there have been examples of immune responses in MUC1 transgenic mice and no signs of autoimmunity noted [27,28]. In mice, we have demonstrated that a 20mer MUC1 VNTR peptide sequence, when coupled to mannan in the oxidized form protected mice from challenge with MUC1 + mouse tumors, generated CTL, T1-type immune responses and mapped H2 and HLA epitopes ( Table 2) [11,12,[29][30][31][32][33]. The peptide mimetic to be identified must generate CTL response and mimic the association with MHC class I molecules.…”

Section: Muc1 As a Target For Tumor Immuno-therapymentioning

confidence: 99%

Applications of Peptide Mimetics in Cancer

Apostolopoulos¹,

Matsoukas²,

Plebanski³

et al. 2002

CMC

Self Cite

View full text Add to dashboard Cite

The development of a vaccine for cancer has been difficult compared to the effective vaccines of infectious diseases. Most tumor antigens are not entirely foreign and are expressed on normal tissues, thus, making it difficult to induce strong immune responses against self antigens. A peptide mimic, however, may have the potential to generate greater immune responses than those induced to self peptides. In this review we discuss applications of peptide mimics for cancer immunotherapy which may ultimately prove useful in humans.

show abstract

“…MUC1 is highly expressed by the majority of cancers and, in particular, by primary and metastatic breast cancers [3][4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Anti-MUC1 aptamers: radiolabelling with 99mTc and biodistribution in MCF-7 tumour-bearing mice

Pieve

Perkins

Missailidis

2009

Nuclear Medicine and Biology

119

View full text Add to dashboard Cite

Tc, for the potential use as radiopharmaceuticals for diagnostic imaging of breast cancer. Methods:The conjugation was achieved in high yield using standard peptide coupling reactions between an amino modification on the aptamer and the activated carboxylic group on the ligands. The retention of the affinity of the MAG2 modified AptA for the MUC1 protein core was confirmed using a FID binding assay. The 2 labelled aptamers were separated from free 99m Tc using microcon filter separation and monitored by HPLC at all stages, to ensure that only radiolabelled aptamers were produced. The biodistribution properties of the two aptamer-radionuclide conjugates were analysed in MCF-7 tumour bearing mice and compared. Tc. The radiolabelled aptamers showed different tumour uptake and clearance, but will require further development prior to diagnostic use. Results

show abstract

The immunogenicity of MUC1 peptides and fusion protein

Cited by 33 publications

References 14 publications

MUC1 immunotherapy against a metastatic mammary adenocarcinoma model: Importance of IFN-gamma

MUC1 immunotherapy against a metastatic mammary adenocarcinoma model: Importance of IFN-gamma

Applications of Peptide Mimetics in Cancer

Anti-MUC1 aptamers: radiolabelling with 99mTc and biodistribution in MCF-7 tumour-bearing mice

Contact Info

Product

Resources

About