SEREX analysis of gastric cancer antigens

Obata, Yuichi; Takahashi, Toshitada; Sakamoto, Junichi; Tamaki, Hiromi; Tominaga, Suketami; Hamajima, Nobuyuki; Chen, Yao‐Tseng; Old, Lloyd J.

doi:10.1007/pl00014048

Cited by 20 publications

(17 citation statements)

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“…Greiner et al [22] also demonstrated significant antibody response toward MPP11 in the sera of breast cancer patients but not in sera of healthy volunteers. These data contradict the data of Obata et al [21] and Scanlan et al [20] who both failed to show increased immunogenicity of ZRF1 antigen in sera of stomach and breast cancer patients correspondingly compared with sera of healthy women. This concordance was explained by Greiner in part by different cDNAs lengths of SEREX clones that might result in a various conformation of the gene's protein products and subsequently in a different epitope presentation to IgG antibodies [22].…”

Section: Discussioncontrasting

confidence: 99%

Autoantibody Response to ZRF1 and KRR1 SEREX Antigens in Patients with Breast Tumors of Different Histological Types and Grades

et al. 2016

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Purpose. To investigate a frequency of antibody response to SEREX-identified medullary breast carcinoma autoantigens ZRF1 and KRR1 in sera of breast cancer patients taking into account clinical and molecular characteristics of tumors for opening of new perspectives in creation of minimally invasive immunological tests for cancer diagnostics. Methods. Enzyme-linked immunosorbent assay and bioinformatics analysis. Results. Increased frequency of antibody response was found in sera of breast cancer patients to ZRF and KRR1 antigens. The antibody response to these antigens was higher in sera of patients with invasive ductal carcinoma than in sera of patients with other histological types of breast tumors. Moreover, more frequent antibody response to ZRF antigen was found in sera of patients with less aggressive tumors. The sequence analysis of ZRF1 antigen SEREX clones obtained from cDNA libraries of different tumors demonstrates that they encode different protein isoforms. Conclusion. Tumor-associated antigens KRR1 and ZRF1 and their cognate autoantibodies could be considered as potential molecular markers of breast cancer which need to be further investigated.

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Section: Discussioncontrasting

confidence: 99%

Autoantibody Response to ZRF1 and KRR1 SEREX Antigens in Patients with Breast Tumors of Different Histological Types and Grades

et al. 2016

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“…This technology aimed to identify the complete repertoire of immunogenic gene products in human cancer, also known as the "cancer immunome". Several SEREX studies have focused on identifying tumor antigens in melanoma [41,42], esophageal cancer [43], colon cancer [44][45][46], gastric cancer [47][48], renal cancer [49,50] and breast cancer [51,52].…”

Section: Identification Of B Cell Epitopesmentioning

confidence: 99%

Targeting the Immune System in Cancer

Chaudhuri

Suriano²,

Mittelman³

et al. 2009

CPB

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The concept of cancer immunotherapy provides a fresh perspective as it is not associated with many of the drawbacks of conventional therapies such as chemotherapy, radiotherapy and surgery. When fully activated the immune system has immense potential as is evident from mis-matched transplanted organs undergoing rapid immunological attack and rejection. However, the development of immune strategies for cancer therapy has been associated with challenges of their own. Early attempts at cancer vaccination were carried out in an empirical manner that did not always lead to reproducibility. This led to a search of tumor associated antigens with the belief that specific targeting of these antigens would lead to successful tumor elimination. Active vaccination with TAA peptides or passive vaccination with specific lymphocytes against these TAAs did not however demonstrate encouraging results in clinical trials. This was mainly because of the lack of an activating immune response which is required for continuous stimulation of lymphocytes and also because of the selection of tumor escape variants that did not express the particular TAA. On the positive side, attempts at characterizing TAAs illuminated the molecular changes that attribute a malignant phenotype to cancer cells. Attempts at cytokine therapy were also met with challenges of high systemic toxicity and a lack of specific lymphocyte activation. It was therefore realized that an ideal vaccinating agent should be able to combine the effects of both these therapeutic strategies, i.e., it should be able to induce an innate immune response which can be tailored to a tumor specific adaptive immune response. By this, the immunosuppressive tumor environment can be altered to become immune activating, thus facilitating the infiltration of myeloid and lymphoid cells that can act in concert leading to tumor regression. In this regard, immunotherapeutic approaches such as DNA vaccines, dendritic cell based vaccines, HSP based vaccines and gene transfer technology, are being developed and further refined to overcome their inherent limitations. Animal experiments with these therapeutic modalities have demonstrated exciting results, although their evaluation in clinical trials has not indicated exceptional tumor protection in a large percentage of the patients. These observations only further underscore the multivariate and dynamic nature of the immune system and the many ways in which tumor cells modulate themselves and their surroundings to escape immune surveillance. Assessment of successful therapeutic intervention will require periodic evaluations of the suppressive nature of the tumor microenvironment accompanied by qualitative and quantitative measurements of lymphocyte responses in patients. With the development of advanced genetic technologies and continuous identification of tumor antigens, the field of cancer immunotherapy is progressing at an exciting pace giving us hope for the advent of effective treatment modalities that will prolong tumor free survival and enha...

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“…[1][2][3][4][5][6][7][8][9][10][11] The most rapidly expanding group of tumor Ags are the cancer/testis (C/T) Ags, which are either not expressed or are present at very low levels in normal tissues except the testes and perhaps the placenta. 12,13 Because the testes are not patrolled by the immune system, expression of C/T Ags in this environment is not harmful.…”

Section: Introductionmentioning

confidence: 99%

NY-ESO-1 is highly expressed in poor-prognosis multiple myeloma and induces spontaneous humoral and cellular immune responses

Rhee

Szmania

Zhan

et al. 2005

Blood

177

140

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The presence of a metaphase cytogenetic abnormality (CA) is the key negative predictor of outcome in patients with multiple myeloma (MM). Gene expression profiling (GEP) of such patients showed increased expression of NY-ESO-1 compared to patients with normal cytogenetics (60% versus 31%; P ‫؍‬ .004). NY-ESO-1 was also highly expressed in relapsing MM especially patients with CA (100% versus 60.7%; P < .001). GEP findings were confirmed at the protein level by immunostaining of marrow biopsies for NY-ESO-1. We detected spontaneous NY-ESO-1-specific antibodies by enzymelinked immunosorbent assay in 33% of patients with NY-ESO-1 ؉ MM, especially in CA patients (9 of 13; 70%), but in none of the NY-ESO-1 ؊ patients with MM (n ‫؍‬ 27) or healthy donors (n ‫؍‬ 21 IntroductionDuring the past 10 years, numerous human tumor-associated antigens (Ags) have been identified, either by screening cDNA libraries with sera derived from cancer patients containing an antibody (Ab) to a tumor-associated Ag (SEREX) or by using T lymphocytes specific for tumor peptides presented in the context of specific HLA alleles. [1][2][3][4][5][6][7][8][9][10][11] The most rapidly expanding group of tumor Ags are the cancer/testis (C/T) Ags, which are either not expressed or are present at very low levels in normal tissues except the testes and perhaps the placenta. 12,13 Because the testes are not patrolled by the immune system, expression of C/T Ags in this environment is not harmful.Of the C/T Ags described thus far, NY-ESO-1 is among the most immunogenic with not only well-documented spontaneous [14][15][16][17][18][19][20] and vaccine-induced immunity, but also clinical responses in a substantial percentage of chemorefractory cancers. 19,21 NY-ESO-1 mRNA is found in approximately 20% to 40% of tumors including melanoma, prostate, transitional cell bladder, breast, lung, medullary thyroid, squamous head and neck, and cervical carcinoma. 12,14,[22][23][24][25][26][27] Because it is expressed in such a wide variety of tumors, NY-ESO-1 offers a unique opportunity to develop a broad-spectrum tumor-specific cancer vaccine.High-dose chemotherapy with autologous peripheral blood stem cell transplantation (auto-PBSCT) has significantly improved the outcome of patients with multiple myeloma (MM). [28][29][30][31][32][33][34][35][36][37] We and others have shown that the presence of cytogenetic abnormalities (CAs) is the most powerful prognosticator for poor outcome. [38][39][40][41][42][43][44][45] Intensification of treatment in our Total Therapy II (TTII) protocol has resulted in additional improvement in event-free (EFS) and overall survival (OS) of patients without CAs (67% of patients). However, no such improvement has yet been observed for patients with CAs (33% of patients). 41,43,46 Fewer than 10% of patients treated with tandem auto-PBSCT protocols remain in long-term remission and are considered "operationally cured." 40 These data highlight the urgent need for new approaches to improve diseasefree survival in such patients.We analyzed ou...

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SEREX analysis of gastric cancer antigens

Cited by 20 publications

References 0 publications

Autoantibody Response to ZRF1 and KRR1 SEREX Antigens in Patients with Breast Tumors of Different Histological Types and Grades

Autoantibody Response to ZRF1 and KRR1 SEREX Antigens in Patients with Breast Tumors of Different Histological Types and Grades

Targeting the Immune System in Cancer

NY-ESO-1 is highly expressed in poor-prognosis multiple myeloma and induces spontaneous humoral and cellular immune responses

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