Open Access

Investigation of factors associated with reduced clinical benefits of personalized peptide vaccination for pancreatic cancer

  • Authors:
    • Yoshihiro Uchino
    • Daisuke Muroya
    • Munehiro Yoshitomi
    • Shigeki Shichijo
    • Akira Yamada
    • Tetsuro Sasada
    • Teppei Yamada
    • Koji Okuda
    • Kyogo Itoh
    • Shigeru Yutani
  • View Affiliations

  • Published online on: December 29, 2020     https://doi.org/10.3892/mco.2020.2201
  • Article Number: 39
  • Copyright: © Uchino et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to determine the factors associated with reduced clinical benefits of personalized peptide vaccination (PPV) for pancreatic cancer. Phase II PPV clinical trials comprising 309 (8 non‑advanced and 301 advanced‑stage) patients with pancreatic cancer were conducted. Two to four peptides were selected among a set of 31 different peptides as vaccine candidates for personalized peptide vaccination based on human leukocyte antigen types and preexisting peptide‑specific IgG levels, and subcutaneously injected. The selected peptides were subcutaneously injected. Of the 309 patients, 81 failed to complete the 1st PPV cycle due to rapid disease progression, and their median overall survival [2.1 months; 95% confidence interval (CI), 1.8‑2.7] was significantly shorter than that of the remaining 228 patients (8.4 months; 95% CI, 8.4‑9.9; P<0.01). ‘Immune boosting’ was defined when IgG levels before vaccination increased more than 2‑fold after vaccination. Immune boosting was observed in the majority of patients with PPV irrespective of whether or not they received concomitant chemotherapy. Additionally, patients demonstrating immune boosting exhibited longer survival rates. Although the positive‑response rates and peptide‑specific IgG levels in pre‑ and post‑vaccination samples differed among the 31 peptides, patients exhibiting immune boosting in response to each of the vaccinated peptides demonstrated longer survival times. Pre‑vaccination factors associated with reduced clinical benefits were high c‑reactive protein (CRP) levels, high neutrophil counts, lower lymphocyte and red blood cell counts, advanced disease stage and the greater number of chemotherapy courses prior to the PPV treatment. The post‑vaccination factors associated with lower clinical benefits were PPV monotherapy and lower levels of immune boosting. In conclusion, pre‑vaccination inflammatory signatures, rather than pre‑ or post‑vaccination immunological signatures, were associated with reduced clinical benefits of personalized peptide vaccination (PPV) for pancreatic cancer.
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February-2021
Volume 14 Issue 2

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Spandidos Publications style
Uchino Y, Muroya D, Yoshitomi M, Shichijo S, Yamada A, Sasada T, Yamada T, Okuda K, Itoh K, Yutani S, Yutani S, et al: Investigation of factors associated with reduced clinical benefits of personalized peptide vaccination for pancreatic cancer. Mol Clin Oncol 14: 39, 2021
APA
Uchino, Y., Muroya, D., Yoshitomi, M., Shichijo, S., Yamada, A., Sasada, T. ... Yutani, S. (2021). Investigation of factors associated with reduced clinical benefits of personalized peptide vaccination for pancreatic cancer. Molecular and Clinical Oncology, 14, 39. https://doi.org/10.3892/mco.2020.2201
MLA
Uchino, Y., Muroya, D., Yoshitomi, M., Shichijo, S., Yamada, A., Sasada, T., Yamada, T., Okuda, K., Itoh, K., Yutani, S."Investigation of factors associated with reduced clinical benefits of personalized peptide vaccination for pancreatic cancer". Molecular and Clinical Oncology 14.2 (2021): 39.
Chicago
Uchino, Y., Muroya, D., Yoshitomi, M., Shichijo, S., Yamada, A., Sasada, T., Yamada, T., Okuda, K., Itoh, K., Yutani, S."Investigation of factors associated with reduced clinical benefits of personalized peptide vaccination for pancreatic cancer". Molecular and Clinical Oncology 14, no. 2 (2021): 39. https://doi.org/10.3892/mco.2020.2201