Personalized Peptide Vaccine for Advanced Pancreatic Cancer

707 Background: A previous phase II/III trial using a single cancer peptide vaccine derived from vascular endothelial growth factor receptor (VEGFR)2 for patients with advanced pancreatic cancer did not demonstrate the overall survival (OS) benefit (Yamaue et al. Cancer Sci 2015). However, for the next trial, we conducted a multicenter phase II study using multipeptide cocktail vaccine named OCV-C01 derived from a novel higher immunogenic antigen KIF20A, VEGFR1 and VEGFR2 combined with gemcitabine in postoperative adjuvant setting. Methods: A single-arm multicenter phase II study was performed on 30 patients with pancreatic ductal carcinoma who underwent pancreatectomy. At each 28-day treatment cycle, patients received weekly subcutaneous injection of OCV-C01 for 48 weeks, and gemcitabine was administered intravenously at 1,000 mg/m2 on days 1, 8, and 15 for 24 weeks. Patients were followed for 18 months. The primary endpoint was disease-free survival (DFS) and secondary endpoints included safety, OS and immunological assays on peptide-specific cytotoxic T lymphocyte (CTL) activity and KIF20A expression in resected pancreatic cancer. Results: The median DFS was 15.8 months (95% confidence interval (CI), 11.1-20.6), and the DFS rate at 18 months was 34.6% (95% CI, 18.3-51.6). The median OS was not reached and the OS rate at 18 months was 69.0% (95% CI, 48.8-82.5). The administration of OCV-C01 was well tolerated. In the per protocol set, there were significant differences in DFS between patients with and without KIF20A-specific CTL responses (p = 0.027), and between patients with and without KIF20A expression in resected pancreatic cancer tissues (p = 0.014). In addition, all four patients who underwent R0 resection with KIF20A expression had no recurrence of pancreatic cancer with KIF20A-specific CTL responses. Conclusions: OCV-C01 combined with gemcitabine was tolerable with a favorable median DFS of 15.8 months. In cancer vaccine treatment, positive expression of targeted antigen was essential, and postoperative adjuvant setting was more suitable than advanced state of cancer. Clinical trial information: UMIN000007991.

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Antiangiogenic cancer therapy using peptide vaccine for patients with advanced pancreatic cancer

Suizo ◽

10.2958/suizo.25.53 ◽

2010 ◽

Vol 25 (1) ◽

pp. 53-58

Author(s):

Motoki MIYAZAWA ◽

Hiroki YAMAUE

Keyword(s):

Pancreatic Cancer ◽

Cancer Therapy ◽

Peptide Vaccine ◽

Advanced Pancreatic Cancer

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Phase I/II clinical trial using HLA-A24-restricted peptide vaccine derived from KIF20A for patients with advanced pancreatic cancer

Journal of Translational Medicine ◽

10.1186/1479-5876-11-291 ◽

2013 ◽

Vol 11 (1) ◽

pp. 291 ◽

Cited By ~ 38

Author(s):

Shingo Asahara ◽

Kazuyoshi Takeda ◽

Kenji Yamao ◽

Hiroyuki Maguchi ◽

Hiroki Yamaue

Keyword(s):

Pancreatic Cancer ◽

Clinical Trial ◽

Phase I ◽

Peptide Vaccine ◽

Advanced Pancreatic Cancer

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A Neoantigen-Based Peptide Vaccine for Patients With Advanced Pancreatic Cancer Refractory to Standard Treatment

Frontiers in Immunology ◽

10.3389/fimmu.2021.691605 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zheling Chen ◽

Shanshan Zhang ◽

Ning Han ◽

Jiahong Jiang ◽

Yunyun Xu ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

T Cells ◽

Cancer Patients ◽

Peptide Vaccine ◽

Advanced Pancreatic Cancer ◽

Effector Memory ◽

Post Vaccination ◽

Specific Subset ◽

Vaccine Treatment

BackgroundNeoantigens are critical targets to elicit robust antitumor T-cell responses. Personalized cancer vaccines developed based on neoantigens have shown promising results by prolonging cancer patients’ overall survival (OS) for several cancer types. However, the safety and efficacy of these vaccine modalities remains unclear in pancreatic cancer patients.MethodsThis retrospective study enrolled 7 advanced pancreatic cancer patients. Up to 20 neoantigen peptides per patient identified by our in-house pipeline iNeo-Suite were selected, manufactured and administered to these patients with low tumor mutation burden (TMB) (less than 10 mutations/Mb). Each patient received multiple doses of vaccine depending on the progression of the disease. Peripheral blood samples of each patient were collected pre- and post-vaccination for the analysis of the immunogenicity of iNeo-Vac-P01 through ELISpot assay and flow cytometry.ResultsNo severe vaccine-related adverse effects were witnessed in patients enrolled in this study. The mean OS, OS associated with vaccine treatment and progression free survival (PFS) were reported to be 24.1, 8.3 and 3.1 months, respectively. Higher peripheral IFN-γ titer and CD4+ or CD8+ effector memory T cells count post vaccination were found in patients with relatively long overall survival. Remarkably, for patient P01 who had a 21-month OS associated with vaccine treatment, the abundance of antigen-specific TCR clone drastically increased from 0% to nearly 100%, indicating the potential of iNeo-Vac-P01 in inducing the activation of a specific subset of T cells to kill cancer cells.ConclusionsNeoantigen identification and selection were successfully applied to advanced pancreatic cancer patients with low TMB. As one of the earliest studies that addressed an issue in treating pancreatic cancer with personalized vaccines, it has been demonstrated that iNeo-Vac-P01, a personalized neoantigen-based peptide vaccine, could improve the currently limited clinical efficacy of pancreatic cancer.Clinical Trial RegistrationClinicalTrials.gov, identifier (NCT03645148).Registered August 24, 2018 - Retrospectively registered

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Juzentaihoto Failed to Augment Antigen-Specific Immunity but Prevented Deterioration of Patients’ Conditions in Advanced Pancreatic Cancer under Personalized Peptide Vaccine

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/981717 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Shigeru Yutani ◽

Nobukazu Komatsu ◽

Satoko Matsueda ◽

Munehiro Yoshitomi ◽

Takahisa Shirahama ◽

...

Keyword(s):

Pancreatic Cancer ◽

Clinical Study ◽

Immune Responses ◽

Cancer Patients ◽

Peptide Vaccine ◽

Advanced Pancreatic Cancer ◽

Clinical Effects ◽

Specific Immunity ◽

Randomized Clinical Study ◽

Vaccine Antigens

Juzentaihoto (JTT) is a well-known Japanese herbal medicine, which has been reported to modulate immune responses and enhance antitumor immunity in animal models. However, it is not clear whether JTT has similar effects on humans. In particular, there is little information on the effects of JTT in antigen-specific immunity in cancer patients. Here we conducted a randomized clinical study to investigate whether combined usage of JTT could affect antigen-specific immunity and clinical findings in advanced pancreatic cancer patients undergoing personalized peptide vaccination (PPV), in which HLA-matched vaccine antigens were selected based on the preexisting host immunity. Fifty-seven patients were randomly assigned to receive PPV with (n=28) or without (n=29) JTT. Unexpectedly, JTT did not significantly affect cellular or humoral immune responses specific to the vaccine antigens, which were determined by antigen-specific interferon-γsecretion in T cells and antigen-specific IgG titers in plasma, respectively. Nevertheless, JTT prevented deterioration of patients’ conditions, such as anemia, lymphopenia, hypoalbuminemia, plasma IL-6 elevation, and reduction of performance status, which are frequently observed in advanced cancers. To our knowledge, this is the first clinical study that examined the immunological and clinical effects of JTT in cancer patients undergoing immunotherapy in humans.

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