Mucin-Like Carcinoma-Associated Antigen Serum Levels in Patients with Adenocarcinomas Originating from Ovary, Breast and Colon

Bon, G.G.; Verheijen, R.; Zuetenhorst, Johanna M.; Kamp, Gerard J. van; Verstraeten, A.A.; Kenemans, P.

doi:10.1159/000291890

Cited by 9 publications

(4 citation statements)

References 10 publications

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“…3 In the vast majority of human adenocarcinomas this protein is over-expressed and hypo-glycosylated 4 exposing an immunodominant repetitive amino acid sequence. The overproduction and secretion of MUC1 is correlated with the progression of breast, 5 ovarian 6,7 and colon 8 carcinoma. In breast cancer patients MUC1 serum levels are used to monitor therapy and for early detection of recurrences.…”

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confidence: 99%

Antibody-dependent cell-mediated cytotoxicity can be induced by MUC1 peptide vaccination of breast cancer patients

et al. 2001

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Key words: MUC1; breast cancer; ADCC; NK cells; vaccination; immunotherapyMUC1 is a transmembrane O-linked glycoprotein present on the apical surface of normal secretory epithelial cells. 1 The extracellular domain of MUC1 consists mainly of a variable number of tandem repeats 2 and it has a cytoplasmatic tail of 69 amino acids. 3 In the vast majority of human adenocarcinomas this protein is over-expressed and hypo-glycosylated 4 exposing an immunodominant repetitive amino acid sequence. The overproduction and secretion of MUC1 is correlated with the progression of breast, 5 ovarian 6,7 and colon 8 carcinoma. In breast cancer patients MUC1 serum levels are used to monitor therapy and for early detection of recurrences. 9,10 Proliferative responses to MUC1 and its tandem-repeat peptides have been demonstrated with peripheral blood mononuclear cells (PBMC) of patients with ovarian adenocarcinoma 11 and MUC1 specific cytotoxic T lymphocytes (CTL) have been isolated from tumor-draining lymph nodes of breast 12 and ovarian 13 cancer patients. In patients with ovarian, breast and pancreatic adenocarcinomas cytotoxic T cells can be induced that are specific for the MUC1 tandem repeat. 14,15 Recognition of MUC1 by T lymphocytes may be due to exposure of the immunogenic PDTRP region of the tandem repeat that is normally not exposed due to extensive O-glycosylation of the peptide core. The cytotoxic action of these T cells has also been described to be MHC-nonrestricted, due to crosslinkage to poorly glycosylated MUC1 tandem repeats on tumor cells. 16 Not only cellular but also humoral responses to MUC1 are found in breast, ovarian, colon and pancreatic carcinomas. [17][18][19] Moreover, the presence of immune-complexed MUC1 in breast cancer patients is related to a favorable disease outcome 20 and survival in early breast cancer patients is favorably influenced by a natural humoral immune response to MUC1. 21 These findings point to MUC1 and its repeat peptide as a target for immunotherapy of carcinomas. One possible approach is the use of MAbs against tumor-associated antigens, 22,23 another the use of tumorassociated antigens such as MUC1 as a vaccine and target for cellular and humoral immune responses.MUC1 MAbs have already been used in a number of vaccination trials as carrier molecule of radioactive elements 24,25 and recently a clinical trial has been set up with unlabeled humanized (Hu)HMFG-1 MAb for adjuvant therapy of breast cancer patients (Dr. D.W. Miles, Guy's Hospital, London). Also active vaccination trials with MUC1 tandem-repeat peptides 26 have been initiated. Recently, in 3 phase I vaccination trials executed by Dr. P.O. Livingston in the Memorial Sloan-Kettering Cancer Center, NY, breast cancer patients with no evidence of disease were repeatedly injected with a 30-mer 27,28 a 33-mer or a 106-mer MUC1 tandem repeat peptide conjugated to KLH plus adjuvant QS-21. In these patients high MUC1 IgG and IgM could be induced. 21 MAbs specific for tumor-associated antigens (TAA) can induce a complement-depende...

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confidence: 99%

Antibody-dependent cell-mediated cytotoxicity can be induced by MUC1 peptide vaccination of breast cancer patients

et al. 2001

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“…30 Circulating mucin-1, also referred to as cancer antigen 15-3, can also be detected in the sera of cancer patients. 45,46 Antibodies against mucin-1 have been described in breast, ovarian, pancreatic, and colon cancer patients. In breast cancer patients, an inverse relationship between circulating levels of mucin-1 and mucin-1 antibodies has been reported.…”

Section: Discussionmentioning

confidence: 99%

Can Breast Implants Induce Breast Cancer Immunosurveillance? An Analysis of Antibody Response to Breast Cancer Antigen following Implant Placement

Fracol

Shah

Dolivo

et al. 2021

Plastic &Amp; Reconstructive Surgery

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Background: Women with cosmetic breast implants have significantly lower rates of subsequent breast cancer than the general population (relative risk, 0.63; 95 percent CI, 0.56 to 0.71). The authors hypothesize that breast implant-induced local inflammation stimulates immunosurveillance recognition of breast tumor antigen. Methods: Sera were collected from two cohorts of healthy women: women with long-term breast implants (i.e., breast implants for >6 months) and breast implant-naive women. Antibody responses to breast tumor antigens were tested by enzyme-linked immunosorbent assay and compared between cohorts by unpaired t test. Of the implant-naive cohort, nine women underwent breast augmentation, and antibody responses before and after implant placement were compared by paired t test. Results: Sera were collected from 104 women: 36 (34.6 percent) long-term breast implants and 68 (65.4 percent) implant-naive women. Women with long-term breast implants had higher antibody responses than implant-naive women to mammaglobin-A (optical density at 450 nm, 0.33 versus 0.22; p = 0.003) and mucin-1 (optical density at 450 nm, 0.42 versus 0.34; p = 0.02). There was no difference in antibody responses to breast cancer susceptibility gene 2, carcinoembryonic antigen, human epidermal growth factor receptor-2, or tetanus. Nine women with longitudinal samples preoperatively and 1 month postoperatively demonstrated significantly elevated antibody responses following implant placement to mammaglobin-A (mean difference, 0.13; p = 0.0002) and mucin-1 (mean difference 0.08; p = 0.02). There was no difference in postimplant responses to other breast tumor antigens, or tetanus. Conclusions: Women with long-term breast implants have higher antibody recognition of mammaglobin-A and mucin-1. This study provides the first evidence of implant-related immune responses to breast cancer antigens. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

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“…In addition, it was noted that the over-expression of MUC1, a human tumor-associated epithelial mucin, is correlated with the progression of breast [81], ovarian [82], and colon [83] cancer. Structurally, MUC1 contains repeating units of a 20-amino acid sequence (HGVTSAPDTRPAPGSTAPPA) in the extracellular portion of this glycoprotein [84].…”

Section: Dual Acting Vaccinesmentioning

confidence: 99%

Synthetic carbohydrate-based anticancer vaccines: the Memorial Sloan-Kettering experience

Zhu¹,

Warren

Danishefsky³

2009

Expert Review of Vaccines

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SummaryMalignantly transformed cells can express aberrant cell surface glycosylation patterns, which serve to distinguish them from normal cells. This phenotype provides an opportunity for the development of carbohydrate-based vaccines for cancer immunotherapy. Synthetic carbohydratebased vaccines, properly introduced through vaccination of a subject with a suitable construct, should be recognized by the immune system. Antibodies induced against these carbohydrate antigens could then participate in the eradication of carbohydrate-displaying tumor cells. Advances in carbohydrate synthetic capabilities have allowed us to efficiently prepare a range of complex, synthetic anticancer vaccine candidates. We describe herein the progression of our longstanding carbohydrate-based anticancer vaccine program, which is now at the threshold of clinical evaluation in several contexts. Our carbohydrate-based anticancer vaccine program has evolved through a number of stages: (1) monomeric vaccines; (2) monomeric clustered vaccines; (3) unimolecular multi-antigenic vaccines; (4) dual acting vaccines. This account will focus on our recently developed unimolecular multi-antigenic constructs and potential dual-acting constructs, which contain clusters of both carbohydrate and peptide epitopes.

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Mucin-Like Carcinoma-Associated Antigen Serum Levels in Patients with Adenocarcinomas Originating from Ovary, Breast and Colon

Cited by 9 publications

References 10 publications

Antibody-dependent cell-mediated cytotoxicity can be induced by MUC1 peptide vaccination of breast cancer patients

Antibody-dependent cell-mediated cytotoxicity can be induced by MUC1 peptide vaccination of breast cancer patients

Can Breast Implants Induce Breast Cancer Immunosurveillance? An Analysis of Antibody Response to Breast Cancer Antigen following Implant Placement

Synthetic carbohydrate-based anticancer vaccines: the Memorial Sloan-Kettering experience

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