Immunoglobulin Allotypes Influence Antibody Responses to Mucin 1 in Patients with Gastric Cancer

Pandey, Janardan P.; Nietert, Paul J.; Mensdorff‐Pouilly, Silvia von; Klaamas, Kersti; Kurtenkov, Oleg

doi:10.1158/0008-5472.can-07-5607

Cited by 15 publications

(10 citation statements)

References 38 publications

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“…Hepatitis C virus (HCV) infected patients with the Gm1,17 5,13 phenotype within an African American population had two-fold higher median antibody titres against E1 and E2 envelope glycoproteins, HCV epitopes than those who lacked this phenotype [17]. In a study on the association of allotypes with antibodies against MUC1, a tumor-associated antigen, gastric cancer patients with the phenotype Gm3 23 5, 13 had lower anti-MUC1-IgG levels compared to patients without this phenotype [18]. …”

Section: Discussionmentioning

confidence: 99%

Surprising negative association between IgG1 allotype disparity and anti-adalimumab formation: a cohort study

Bartelds¹,

Groot

Nurmohamed

et al. 2010

Arthritis Res Ther

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IntroductionThe human monoclonal antibody adalimumab is known to induce an anti-globulin response in some adalimumab-treated patients. Antibodies against adalimumab (AAA) are associated with non-response to treatment. Immunoglobulins, such as adalimumab, carry allotypes which represent slight differences in the amino acid sequences of the constant chains of an IgG molecule. Immunoglobulins with particular IgG (Gm) allotypes are racially distributed and could be immunogenic for individuals who do not express these allotypes. Therefore, we investigated whether a mismatch in IgG allotypes between adalimumab and IgG in adalimumab-treated patients is associated with the development of AAA.MethodsThis cohort study consisted of 250 adalimumab-treated rheumatoid arthritis (RA) patients. IgG allotypes were determined for adalimumab and for all patients. Anti-idiotype antibodies against adalimumab were measured with a regular radio immunoassay (RIA), and a newly developed bridging enzyme linked immunosorbent assay (ELISA) was used to measure anti-allotype antibodies against adalimumab. The association between AAA and the G1m3 and the G1m17 allotypes was determined. For differences between groups we used the independent or paired samples t-test, Mann-Whitney test or Chi square/Fisher's exact test as appropriate. To investigate the influence of confounders on the presence or absence of AAA a multiple logistic regression-analysis was used.ResultsAdalimumab carries the G1m17 allotype. No anti-allotype antibodies against adalimumab were detected. Thirty-nine out of 249 patients had anti-idiotype antibodies against adalimumab (16%). IgG allotypes of RA patients were associated with the frequency of AAA: patients homozygous for G1m17 had the highest frequency of AAA (41%), patients homozygous for G1m3 the lowest frequency (10%), and heterozygous patients' AAA frequency was 14% (P = 0.0001).ConclusionsAn allotype mismatch between adalimumab and IgG in adalimumab-treated patients did not lead to a higher frequency of AAA. On the contrary, patients who carried the same IgG allotype as present on the adalimumab IgG molecule, had the highest frequency of anti-adalimumab antibodies compared to patients whose IgG allotype differed from adalimumab. This suggests that the allotype of adalimumab may not be highly immunogenic. Furthermore, patients carrying the G1m17-allotype might be more prone to antibody responses.

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Section: Discussionmentioning

confidence: 99%

Surprising negative association between IgG1 allotype disparity and anti-adalimumab formation: a cohort study

Bartelds¹,

Groot

Nurmohamed

et al. 2010

Arthritis Res Ther

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“…The same study demonstrated that down-regulation of the p300 HAT gene by RNA interference abrogated the effect of anacardic acid on NF-κB suppression. Further nutraceuticals including the soy isoflavone genistein (Raffoul et al, 2006), the isoquinoline alkaloid berberine from medicinal plants such as Berberis aristata , Coptis chinensis , Coptis japonica , Coscinium fenestratum , and Hydrastis canadensis (Pandey et al, 2008), piceatannol (3,3 ′ ,4,5 ′ -trans-trihydroxystilbene), a naturally occurring hydroxylated analog of resveratrol found in various plants (Son et al, 2010), the principal prenylated flavonoid xanthohumol from Humulus lupulus (Harikumar et al, 2009), and the polyphenol butein (3,4,2 ′ ,4 ′ -tetrahydroxychalcone) from Rhus verniciflua Stokes (Pandey et al, 2007) have been identified as blocking NF-κB by direct interaction with IKKβ on cysteine 179 residue. NF-κB inhibition by direct interaction with one of its subunits occurs in the presence of numerous phytochemicals including sesquiterpene lactones (Garcia-Pineres et al, 2001).…”

Section: Nf-κb Inhibitionmentioning

confidence: 99%

Radiation, Inflammation, and Immune Responses in Cancer

Multhoff¹,

Radons²

2012

Front. Oncol.

162

128

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Chronic inflammation has emerged as one of the hallmarks of cancer. Inflammation also plays a pivotal role in modulating radiation responsiveness of tumors. As discussed in this review, ionizing radiation (IR) leads to activation of several transcription factors modulating the expression of numerous mediators in tumor cells and cells of the microenvironment promoting cancer development. Novel therapeutic approaches thus aim to interfere with the activity or expression of these factors, either in single-agent or combinatorial treatment or as supplements of the existing therapeutic concepts. Among them, NF-κB, STAT-3, and HIF-1 play a crucial role in radiation-induced inflammatory responses embedded in a complex inflammatory network. A great variety of classical or novel drugs including nutraceuticals such as plant phytochemicals have the capacity to interfere with the inflammatory network in cancer and are considered as putative radiosensitizers. Thus, targeting the inflammatory signaling pathways induced by IR offers the opportunity to improve the clinical outcome of radiation therapy by enhancing radiosensitivity and decreasing putative metabolic effects. Since inflammation and sex steroids also impact tumorigenesis, a therapeutic approach targeting glucocorticoid receptors and radiation-induced production of tumorigenic factors might be effective in sensitizing certain tumors to IR.

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“…Furthermore, initial studies suggest an association between GM allotypes, genetic markers of IgG heavy chains, and levels of MUC1 IgG abs that may have an implication for immunotherapy [72,73]. …”

Section: Natural Antibodies To Muc1mentioning

confidence: 99%

Natural and Induced Humoral Responses to MUC1

Mensdorff‐Pouilly

Moreno

Verheijen

2011

Cancers

Self Cite

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MUC1 is a membrane-tethered mucin expressed on the ductal cell surface of glandular epithelial cells. Loss of polarization, overexpression and aberrant glycosylation of MUC1 in mucosal inflammation and in adenocarcinomas induces humoral immune responses to the mucin. MUC1 IgG responses have been associated with a benefit in survival in patients with breast, lung, pancreatic, ovarian and gastric carcinomas. Antibodies bound to the mucin may curb tumor progression by restoring cell-cell interactions altered by tumor-associated MUC1, thus preventing metastatic dissemination, as well as counteracting the immune suppression exerted by the molecule. Furthermore, anti-MUC1 antibodies are capable of effecting tumor cell killing by antibody-dependent cell-mediated cytotoxicity. Although cytotoxic T cells are indispensable to achieve anti-tumor responses in advanced disease, abs to tumor-associated antigens are ideally suited to address minimal residual disease and may be sufficient to exert adequate immune surveillance in an adjuvant setting, destroying tumor cells as they arise or maintaining occult disease in an equilibrium state. Initial evaluation of MUC1 peptide/glycopeptide mono and polyvalent vaccines has shown them to be immunogenic and safe; anti-tumor responses are scarce. Progress in carbohydrate synthesis has yielded a number of sophisticated substrates that include MUC1 glycopeptide epitopes that are at present in preclinical testing. Adjuvant vaccination with MUC1 glycopeptide polyvalent vaccines that induce strong humoral responses may prevent recurrence of disease in patients with early stage carcinomas. Furthermore, prophylactic immunotherapy targeting MUC1 may be a strategy to strengthen immune surveillance and prevent disease in subjects at hereditary high risk of breast, ovarian and colon cancer.

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Immunoglobulin Allotypes Influence Antibody Responses to Mucin 1 in Patients with Gastric Cancer

Cited by 15 publications

References 38 publications

Surprising negative association between IgG1 allotype disparity and anti-adalimumab formation: a cohort study

Surprising negative association between IgG1 allotype disparity and anti-adalimumab formation: a cohort study

Radiation, Inflammation, and Immune Responses in Cancer

Natural and Induced Humoral Responses to MUC1

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