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

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.

SUBMITTER: Uchino Y

PROVIDER: S-EPMC7788558 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Project description:IntroductionSince treatment modalities for metastatic recurrent triple-negative breast cancer (mrTNBC) are limited, a novel treatment approach including immunotherapy is required. We have developed a novel regimen of personalized peptide vaccination (PPV), in which vaccine antigens are individually selected from a pool of different peptide candidates based on the pre-existing host immunity. Herein we conducted a phase II study of PPV for metastatic recurrent breast cancer patients to investigate the feasibility of PPV for mrTNBC.MethodsSeventy-nine patients with metastatic recurrent breast cancer who had metastases and had failed standard chemotherapy and/or hormonal therapy were enrolled. They were subgrouped as the mrTNBC group (n = 18), the luminal/human epidermal growth factor receptor 2 (HER2)-negative group (n = 41) and the HER2-positive group (n = 18), while the remaining two patients had not been investigated. A maximum of four human leukocyte antigen (HLA)-matched peptides showing higher peptide-specific immunoglobulin G (IgG) responses in pre-vaccination plasma were selected from 31 pooled peptide candidates applicable for the four HLA-IA phenotypes (HLA-A2, -A24, or -A26 types, or HLA-A3 supertypes), and were subcutaneously administered weekly for 6 weeks and bi-weekly thereafter. Measurement of peptide-specific cytotoxic T lymphocyte (CTL) and IgG responses along with other laboratory analyses were conducted before and after vaccination.ResultsNo severe adverse events associated with PPV were observed in any of the enrolled patients. Boosting of CTL and/or IgG responses was observed in most of the patients after vaccination, irrespective of the breast cancer subtypes. There were three complete response cases (1 mrTNBC and 2 luminal/HER2-negative types) and six partial response cases (1 mrTNBC and 5 luminal/HER2-negative types). The median progression-free survival time and median overall survival time of mrTNBC patients were 7.5 and 11.1 months, while those of luminal/HER2-negative patients were 12.2 and 26.5 months, and those of HER2-positive patients were 4.5 and 14.9 months, respectively.ConclusionsPPV could be feasible for mrTNBC patients because of the safety, immune responses, and possible clinical benefits.Clinical trial registration numberUMIN000001844 (Registration Date: April 5, 2009).

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

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