Vaccination with peptides derived from cancer-testis antigens in combination with CpG-7909 elicits strong specific CD8+ T cell response in patients with metastatic esophageal squamous cell carcinoma - PubMed (original) (raw)
Clinical Trial
Vaccination with peptides derived from cancer-testis antigens in combination with CpG-7909 elicits strong specific CD8+ T cell response in patients with metastatic esophageal squamous cell carcinoma
Makoto Iwahashi et al. Cancer Sci. 2010 Dec.
Abstract
Potent helper action is necessary for peptide-based vaccines to efficiently induce antitumor immune responses against advanced cancer. A phase I trial for advanced esophageal squamous cell carcinoma was carried out for patients with HLA-A*2402 using epitope peptides derived from novel cancer-testis antigens, LY6K and TTK, in combination with CpG-7909 (NCT00669292). This study investigated the feasibility and the toxicity as well as induction of tumor antigen-specific immune responses. Nine patients were vaccinated on days 1, 8, 15, and 22 of each 28-day treatment cycle with peptide LY6K-177, peptide TTK-567, and CpG-7909 (level-1; 0, level-2; 0.02, level-3; 0.1 mg/kg) and all were tolerated by this treatment. LY6K-specific T cell responses in PBMCs were detected in two of the three patients in each level. In particular, two patients in level-2/3 showed potent LY6K-specific T cell responses. In contrast, only two patients in level-2/3 showed TTK-567-specific T cell responses. The frequency of LY6K-177 or TTK-567-specific CD8+ T cells increased in patients in level-2/3 (with CpG). The vaccination with peptides and CpG-7909 increased and activated both plasmacytoid dendritic cells and natural killer cells, and increased the serum level of α-interferon. There were no complete response (CR) and partial response (PR), however, one of three patients in level-1, and four of six patients in level-2/3 showed stable disease (SD). In conclusion, vaccination with LY6K-177 and TTK-567 in combination with CpG-7909 successfully elicited antigen-specific CD8+ T cell responses and enhanced the innate immunity of patients with advanced esophageal squamous cell carcinoma. This vaccine protocol is therefore recommended to undergo further phase II trials.
© 2010 Japanese Cancer Association.
Figures
Figure 1
(A) Vaccine‐generated LY6K‐177‐specific T cell response. LY6K‐specific T cell responses were assessed by enzyme‐linked immunosorbent spot assay. The PBMCs were cultured with LY6K‐177 peptide for 2 weeks. On day 7, cells were restimulated with LY6K‐177 peptide. The harvested cells were used as responder cells and LY6K‐177‐pulsed TISI cells were used as stimulator cells. HLA‐A*2402‐restricted epitope peptide derived from HIV‐Env protein was used as the negative control peptide. Spots were captured and analyzed using ImmunoSPOT 4S. Responder cells were mixed with stimulator cells at different ratio, and incubated for 24 h. The _X_‐axis of the figure indicates the responder to stimulator (R/S) ratio. The _Y_‐axis indicates the number of specific spots. (B) Vaccine‐generated TTK‐567‐specific T cell response. TTK‐specific T cell responses were assessed by enzyme‐linked immunosorbent spot assay. The PBMCs were cultured with TTK‐567 peptide for 2 weeks. The cells were restimulated with TTK‐567 peptide on day 7. The harvested cells were used as responder cells and TTK‐567‐pulsed TISI cells were used as stimulator cells. HLA‐A*2402‐restricted epitope peptide derived from HIV‐Env protein was used as the negative control peptide. Responder cells were mixed with stimulator cells at different ratios, and incubated for 24 h. Spots were captured and analyzed using ImmunoSPOT 4S. The _X_‐axis of the figure indicates the R/S ratio. The _Y_‐axis indicates the number of specific spots.
Figure 2
Frequencies of LY6K/TTK‐specific CD8+ T cells in patients with advanced esophageal squamous cell carcinoma, evaluated by HLA‐A*2402/LY6K‐177 (A) or TTK‐567 (C) pentamer staining. The PBMCs were incubated with phycoerythrin‐labeled HLA‐A*2402 presenting LY6K/TTK for 10 min. We added 7‐AAD, and cells were incubated with Fluorotag and FITC‐conjugated anti‐human CD8 mAb, then analyzed using a FACSCalibur. (B) The representative dot plot data of pentamer staining derived from two positive cases, case 6 and 8.
Figure 3
Effect of vaccination on the population of PBMCs in patients with advanced esophageal squamous cell carcinoma. The phenotypical analysis of PBMCs was carried out using a FACSCalibur with CellQuest software before and after vaccination. Data are expressed as the percent change of the positive cell populations. A percent change of 1.5 times was defined as increase. (A) BDCA2+. (B) CD80+/BDCA2+. (C) CD86+/BDCA2+. (D) CD56+. (E) CD69+/CD56+.
Similar articles
- Detection of novel cancer-testis antigen-specific T-cell responses in TIL, regional lymph nodes, and PBL in patients with esophageal squamous cell carcinoma.
Mizukami Y, Kono K, Daigo Y, Takano A, Tsunoda T, Kawaguchi Y, Nakamura Y, Fujii H. Mizukami Y, et al. Cancer Sci. 2008 Jul;99(7):1448-54. doi: 10.1111/j.1349-7006.2008.00844.x. Epub 2008 Apr 30. Cancer Sci. 2008. PMID: 18452554 Free PMC article. - Identification of human leukocyte antigen-A24-restricted epitope peptides derived from gene products upregulated in lung and esophageal cancers as novel targets for immunotherapy.
Suda T, Tsunoda T, Daigo Y, Nakamura Y, Tahara H. Suda T, et al. Cancer Sci. 2007 Nov;98(11):1803-8. doi: 10.1111/j.1349-7006.2007.00603.x. Cancer Sci. 2007. PMID: 17784873 Free PMC article. - Vaccination with multiple peptides derived from novel cancer-testis antigens can induce specific T-cell responses and clinical responses in advanced esophageal cancer.
Kono K, Mizukami Y, Daigo Y, Takano A, Masuda K, Yoshida K, Tsunoda T, Kawaguchi Y, Nakamura Y, Fujii H. Kono K, et al. Cancer Sci. 2009 Aug;100(8):1502-9. doi: 10.1111/j.1349-7006.2009.01200.x. Epub 2009 May 14. Cancer Sci. 2009. PMID: 19459850 Free PMC article. Clinical Trial. - Peptide-based vaccination and induction of CD8+ T-cell responses against tumor antigens in breast cancer.
Harao M, Mittendorf EA, Radvanyi LG. Harao M, et al. BioDrugs. 2015 Feb;29(1):15-30. doi: 10.1007/s40259-014-0114-1. BioDrugs. 2015. PMID: 25523015 Review. - Expression of cancer-testis antigens in esophageal cancer and their progress in immunotherapy.
Zhang Y, Zhang Y, Zhang L. Zhang Y, et al. J Cancer Res Clin Oncol. 2019 Feb;145(2):281-291. doi: 10.1007/s00432-019-02840-3. Epub 2019 Jan 17. J Cancer Res Clin Oncol. 2019. PMID: 30656409 Free PMC article. Review.
Cited by
- An Open-Label Study of Subcutaneous CpG Oligodeoxynucleotide (PF03512676) in Combination with Trastuzumab in Patients with Metastatic HER2+ Breast Cancer.
Quiroga D, Wesolowski R, Zelinskas S, Pinette A, Benner B, Schwarz E, Savardekar H, Johnson C, Stiff A, Yu L, Macrae E, Lustberg M, Mrozek E, Ramaswamy B, Carson WE 3rd. Quiroga D, et al. Cancer Control. 2024 Jan-Dec;31:10732748241250189. doi: 10.1177/10732748241250189. Cancer Control. 2024. PMID: 38797949 Free PMC article. Clinical Trial. - Cancer testis antigens: Emerging therapeutic targets leveraging genomic instability in cancer.
Naik A, Lattab B, Qasem H, Decock J. Naik A, et al. Mol Ther Oncol. 2024 Jan 26;32(1):200768. doi: 10.1016/j.omton.2024.200768. eCollection 2024 Mar 21. Mol Ther Oncol. 2024. PMID: 38596293 Free PMC article. Review. - Toll-like receptor agonists as cancer vaccine adjuvants.
Jeon D, Hill E, McNeel DG. Jeon D, et al. Hum Vaccin Immunother. 2024 Dec 31;20(1):2297453. doi: 10.1080/21645515.2023.2297453. Epub 2023 Dec 28. Hum Vaccin Immunother. 2024. PMID: 38155525 Free PMC article. Review. - A narrative review of the emerging role of lymphocyte antigen 6 complex locus K in cancer: from basic research to clinical practice.
Guo D, Liu Y, Jiang Y, Zheng S, Xu T, Zhu J, Chen P, Huang P, Zhang Y. Guo D, et al. Ann Transl Med. 2022 Jan;10(1):26. doi: 10.21037/atm-21-5831. Ann Transl Med. 2022. PMID: 35242871 Free PMC article. Review. - Efficacy and Safety of Immune Checkpoint Inhibitor in Advanced Esophageal Squamous Cell Carcinoma: A Meta-Analysis.
Gu YM, Shang QX, Zhuo Y, Zhou JF, Liu BW, Wang WP, Che GW, Chen LQ. Gu YM, et al. Front Oncol. 2021 Dec 21;11:777686. doi: 10.3389/fonc.2021.777686. eCollection 2021. Front Oncol. 2021. PMID: 34993139 Free PMC article.
References
- Ando N, Iizuka T, Ide H et al. Surgery plus chemotherapy compared with surgery alone for localized squamous cell carcinoma of the thoracic esophagus: a Japan Clinical Oncology Group Study – JCOG9204. J Clin Oncol 2003; 21: 4592–6. - PubMed
- Hironaka S, Ohtsu A, Boku N et al. Nonrandomized comparison between definitive chemoradiotherapy and radical surgery in patients with T2‐3Nany M0 squamous cell carcinoma of the esophagus. Int J Radiat Oncol Biol Phys 2003; 57: 425–33. - PubMed
- Bedenne L, Michel P, Bouché O et al. Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol 2007; 25: 1160–8. - PubMed
- Boon T. Tumor antigens recognized by cytolytic T lymphocytes: present perspectives for specific immunotherapy. Int J Cancer 1993; 54: 177–80. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials