Vaccination with multiple peptides derived from novel cancer‐testis antigens can induce specific T‐cell responses and clinical responses in advanced esophageal cancer

Kono, Koji; Matsuo, Yoshiki; Daigo, Yataro; Takano, Atsushi; Masuda, Ken; Yoshida, Kōji; Tsunoda, Takuya; Kawaguchi, Yoshihiko; Nakamura, Yusuke; Fujii, Hideki

doi:10.1111/j.1349-7006.2009.01200.x

Cited by 125 publications

(121 citation statements)

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“…The immunogenicity of LY6K-177 peptide vaccine therapy in patients with unresectable advanced esophageal cancer has also been demonstrated [13,14]. We obtained similar results in an esophageal cancer patient, raising hopes for a new treatment option using this peptide.…”

Section: Introductionsupporting

confidence: 72%

“…This finding identifies LY6K as a promising target for immunotherapy. A clinical trial of vaccine therapy with LY6K as the target was previously reported [13,14]; however, expression in gastric cancer has not yet been reported. We expected vaccine therapy with LY6K as the target tobe effective because immunohistochemistry confirmed expression in 85 % of gastric cancers.…”

Section: Discussionmentioning

confidence: 99%

“…LY6K overexpression has been confirmed in several malignancies including head and neck squamous cell carcinomas as well as breast, lung, bladder, and esophageal cancers [12,13,[15][16][17][18][19]. LY6K overexpression is associated with a poorer prognosis in patients with non-small cell lung carcinomas as well as those with esophageal squamous cell carcinomas [12].…”

Section: Discussionmentioning

confidence: 99%

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Phase I clinical trial of vaccination with LY6K-derived peptide in patients with advanced gastric cancer

et al. 2013

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Background Lymphocyte antigen 6 complex locus K (LY6K) has been identified as a tumor-associated antigen in lung cancers and esophageal squamous cell carcinomas. The immunogenicity of LY6K-177 peptide vaccine therapy has been demonstrated in patients with advanced esophageal cancer. This study extends this treatment to gastric cancer. Methods LY6K expression in clinical samples obtained from gastric cancer patients was examined by immunochemistry. As a phase I clinical trial, the safety and immunogenicity of LY6K-177 peptide vaccine emulsified with Montanide ISA 51 was evaluated in six patients with unresectable advanced gastric cancer. LY6K-177 peptide (1 mg in 1 ml sterile saline) was emulsified with incomplete Freund's adjuvant (1 ml) and intracutaneously administered to the inguinal region or axilla. One treatment course comprised four vaccinations, performed weekly for the first and second treatment courses and biweekly for the third treatment course. Results LY6K expression was confirmed in 85 % of gastric cancer tissues. Induration and redness at the vaccination site (grade I), possibly a delayed-type hypersensitivity reaction, was observed in all patients; however, no systemic toxicology was identified in any patient throughout the observation period. Three of the six patients had stable disease, and a tumor contraction effect was observed in one patient.Conclusions LY6K was expressed in 85 % of observed gastric cancers. Vaccination with LY6K-177 peptide/ Montanide ISA 51 appeared to be tolerated by advanced gastric cancer patients, and moreover anticancer efficacy was suggested. This trial was registered with ClinicalTrial.gov (no. NCT00845611).

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Section: Introductionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Phase I clinical trial of vaccination with LY6K-derived peptide in patients with advanced gastric cancer

et al. 2013

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“…Residual disease after treatment is an important issue, for which specific therapeutic approaches, such as immunotherapy, may be of value. [5][6][7] Immunotherapy of cancer types such as melanoma and non-small lung cancer has demonstrated the clinical relevance of this treatment approach. 8 Optimized peptide and DNA vaccination protocols demonstrate ongoing improvements in immunotherapeutic intervention.…”

Section: Introductionmentioning

confidence: 99%

Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy

Duin¹,

Broyl²,

Knegt³

et al. 2011

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundIn multiple myeloma, expression of cancer testis antigens may provide prognostic markers and potential targets for immunotherapy. Expression at relapse has not yet been evaluated for a large panel of cancer testis antigens which can be classified by varying expression in normal tissue: restricted to testis, expressed in testis and brain and not restricted but selectively expressed in testis. Design and MethodsEvaluation of cancer testis antigen expression was made in newly diagnosed multiple myeloma cases (HOVON-65/GMMG-HD4 trial; n=320) and in relapse cases (APEX, SUMMIT, CREST trials; n=264). Presence of expression using Affymetrix GeneChips was determined for 123 cancer testis antigens. Of these 87 had a frequency of more than 5% in the newly diagnosed and relapsed patients, and were evaluated in detail. ResultsTissue restriction was known for 58 out of 87 cancer testis antigens. A significantly lower frequency of presence calls in the relapsed compared to newly diagnosed cases was found for 3 out of 13 testis restricted genes, 2 out of 7 testis/brain restricted genes, and 17 out of 38 testis selective genes. MAGEC1, MAGEB2 and SSX1 were the most frequent testis-restricted cancer testis antigens in both data sets. Multivariate analysis demonstrated that presence of MAGEA6 and CDCA1 were clearly associated with shorter progression free survival, and presence of MAGEA9 with shorter overall survival in the set of newly diagnosed cases. In the set of relapse cases, presence of CTAG2 was associated with shorter progression free survival and presence of SSX1 with shorter overall survival. ConclusionsRelapsed multiple myeloma reveals extensive cancer testis antigen expression. Cancer testis antigens are confirmed as useful prognostic markers in newly diagnosed multiple myeloma patients and in relapsed multiple myeloma patients.The HOVON-65/GMMG-HD4 trial is registered under Dutch trial register n. respectively.

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“…A CTA peptide vaccination of patients with advanced esophageal cancer showed objective clinical responses. 46 Quintarelli et al 47,48 demonstrated PRAME-specific, cytotoxic lymphocyte cytotoxicity against chronic myelogenous leukemia cells. Goodyear et al 49 demonstrated the presence of CD8 þ , CTA-specific, cytotoxic lymphocytes in patients with MM, which, although the lymphocytes were unable to control tumor cell growth in vivo, lysed MM cells in vitro.…”

Section: Cancer/testis Antigens As Csc Immunotherapy Targetsmentioning

confidence: 99%

Cancer Stem Cells: A Review of Potential Clinical Applications

Podberezin

Wen

Chung-Che

2013

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Cancer stem cells (CSCs) comprise a minor cell population in a tumor; however, they possess selfrenewal capacity and are responsible for tumor recurrence and the emerging issue of tumor resistance. Despite recent advances in the study of pathogenesis and mechanisms of CSC-mediated disease recurrence and multidrug resistance, many questions remain unanswered.Objectives.-To provide an overview of CSC theory and to describe major methods of CSC detection and isolation, with the emphasis on those techniques that are potentially relevant in clinical laboratory practice. Particular attention is given to CSC markers, such as cancer testis antigens, which could become promising targets in the development of immunotherapy in settings of minimal residual disease.Data Sources.-The review is based on analysis of peerreviewed literature cited in PubMed, as well as preliminary results of studies conducted in our laboratory.Conclusions.-Despite a lack of consensus in the scientific community on research methodology, CSCs have demonstrated significant potential as therapeutic targets in the treatment of cancer. Further research of CSC biology and markers will eventually lead to the development of novel therapeutic approaches for targeting these cells to treat resistant and recurrent tumors and minimal residual disease.

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Vaccination with multiple peptides derived from novel cancer‐testis antigens can induce specific T‐cell responses and clinical responses in advanced esophageal cancer

Abstract: We previously identified three novel HLA-A24-restricted epitope peptides, which were derived from three cancer-testis antigens, TTK protein kinase (TTK), lymphocyte antigen 6 complex locus K (LY6K), and insulin-like growth factor (

Cited by 125 publications

References 20 publications

Phase I clinical trial of vaccination with LY6K-derived peptide in patients with advanced gastric cancer

Phase I clinical trial of vaccination with LY6K-derived peptide in patients with advanced gastric cancer

Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy

Cancer Stem Cells: A Review of Potential Clinical Applications

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