Autoantibodies against the signal peptide domain of MUC1 in patients with multiple myeloma: Implications for disease diagnosis and prognosis

Kovjazin, Riva; Dubnik, Anna; Horn, Galit; Smorodinsky, Nechama I.; Hardan, Izhar; Shapira, Michael Y.; Carmon, Lior

doi:10.3892/etm.2012.538

Cited by 10 publications

(18 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since soluble MUC1 SP, was neither detected in patient sera [34] nor in the concentrated supernatant of MUC1-positive tumour cell lines (unpublished observations), we suggest that: (a) As shown (figure 2A) these mechanisms are responsible for only a small fraction of the surface-bound MUC1 SP domain which cannot be detected by our assay, and/or, (b) the MUC1 SP released to the blood is immediately degraded by serum proteases.…”

Section: Discussionmentioning

confidence: 75%

“…MUC1-SP-M was chosen based on an in silico prediction for high density MHC Class II and B-cell epitopes and on the considerable concentration of autoantibodies against this peptide, found in the sera of MM patients [34]. Anti-MUC1-SP-M polyclonal antibodies (positive sera titer at ≤1∶25,000) were obtained in mice (data not presented) and in two immunized rabbits R23 and R32 (positive at titer ≤1∶12,800) (Table 1 and Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, a MUC1-specific humoral response can be generated against MUC1 SP, as manifested by significant elevation of natural autoantibodies in the bloodstream of MM patients but not in healthy donors [34]. Since soluble MUC1 SP was not detected in patient sera [34], it was speculated that the naturally generated autoantibodies were primed by non-MHC-restricted, MUC1-associated tumor cell-bound SP.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cell Surface-Associated Anti-MUC1-Derived Signal Peptide Antibodies: Implications for Cancer Diagnostics and Therapy

Kovjazin¹,

Horn

Smorodinsky

et al. 2014

PLoS ONE

Self Cite

View full text Add to dashboard Cite

The MUC1 tumor associated antigen is highly expressed on a range of tumors. Its broad distribution on primary tumors and metastases renders it an attractive target for immunotherapy. After synthesis MUC1 is cleaved, yielding a large soluble extracellular alpha subunit containing the tandem repeats array (TRA) domain specifically bound, via non-covalent interaction, to a smaller beta subunit containing the transmembrane and cytoplasmic domains. Thus far, inconclusive efficacy has been reported for anti-MUC1 antibodies directed against the soluble alpha subunit. Targeting the cell bound beta subunit, may bypass limitations posed by circulating TRA domains. MUC1’s signal peptide (SP) domain promiscuously binds multiple MHC class II and Class I alleles, which upon vaccination, generated robust T-cell immunity against MUC1-positive tumors. This is a first demonstration of non-MHC associated, MUC1 specific, cell surfaces presence for MUC1 SP domain. Polyclonal and monoclonal antibodies generated against MUC1 SP domain specifically bind a large variety of MUC1-positive human solid and haematological tumor cell lines; MUC1-positive bone marrow derived plasma cells obtained from multiple myeloma (MM)-patients, but not MUC1 negative tumors cells, and normal naive primary blood and epithelial cells. Membranal MUC1 SP appears mainly as an independent entity but also co-localized with the full MUC1 molecule. MUC1-SP specific binding in BM-derived plasma cells can assist in selecting patients to be treated with anti-MUC1 SP therapeutic vaccine, ImMucin. A therapeutic potential of the anti-MUC1 SP antibodies was suggested by their ability to support of complement-mediated lysis of MUC1-positive tumor cells but not MUC1 negative tumor cells and normal naive primary epithelial cells. These findings suggest a novel cell surface presence of MUC1 SP domain, a potential therapeutic benefit for anti-MUC1 SP antibodies in MUC1-positive tumors and a selection tool for MM patients to be treated with the anti-MUC1 SP vaccine, ImMucin.

show abstract

Section: Discussionmentioning

confidence: 75%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cell Surface-Associated Anti-MUC1-Derived Signal Peptide Antibodies: Implications for Cancer Diagnostics and Therapy

Kovjazin¹,

Horn

Smorodinsky

et al. 2014

PLoS ONE

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recent findings showed a significant elevation in the levels of autoantibodies against MUC1 SP in the bloodstream of MM patients, 50 when compared with those measured in healthy donors. Since soluble MUC1 SP was not detected in the sera of these patients, it was speculated that the naturally generated autoantibodies were primed by non-MHC-restricted, tumor MUC1-associated cell-bound SP.…”

Section: Generation Of Humoral Immunitymentioning

confidence: 93%

The use of signal peptide domains as vaccine candidates

Kovjazin¹,

Carmon²

2014

Human Vaccines & Immunotherapeutics

Self Cite

View full text Add to dashboard Cite

“…Binding predictions and scoring for HLA class I alleles (HLA-A, -B, and -C), which most frequently appear in Caucasian, sub-Sahara African, and Southwest Asian populations, and for DR class II were performed as previously described (14,18,19). Briefly, the binding strength of 9-mers to the class I alleles was predicted using BIMAS (http://www-bimas.cit.nih.gov/molbio/hla_bind/) (20).…”

Section: Mhc Binding Predictionsmentioning

confidence: 99%

Characterization of Novel Multiantigenic Vaccine Candidates with Pan-HLA Coverage against Mycobacterium tuberculosis

Kovjazin

Shitrit

Preiss

et al. 2013

Clin. Vaccine Immunol.

Self Cite

View full text Add to dashboard Cite

Autoantibodies against the signal peptide domain of MUC1 in patients with multiple myeloma: Implications for disease diagnosis and prognosis

Cited by 10 publications

References 24 publications

Cell Surface-Associated Anti-MUC1-Derived Signal Peptide Antibodies: Implications for Cancer Diagnostics and Therapy

Cell Surface-Associated Anti-MUC1-Derived Signal Peptide Antibodies: Implications for Cancer Diagnostics and Therapy

The use of signal peptide domains as vaccine candidates

Characterization of Novel Multiantigenic Vaccine Candidates with Pan-HLA Coverage against Mycobacterium tuberculosis

Contact Info

Product

Resources

About