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Immunological efficacy of herbal medicines in prostate cancer patients treated by personalized peptide vaccine.

ABSTRACT: This randomized phase II study investigated the immunological efficacy of herbal medicines (HM) using Hochu-ekki-to and Keishi-bukuryo-gan in combination with personalized peptide vaccination (PPV) for castration-resistant prostate cancer (CRPC). Seventy patients with CRPC were assigned to two arms; PPV plus HM or PPV alone. Two to four peptides were chosen from 31 peptides derived from cancer antigens for a s.c. injection of PPV given eight times according to the patient's human leukocyte antigen type and levels of antigen-specific IgG titer before PPV treatment. Peptide-specific CTL, IgG, regulatory T cells (Treg), monocytic myeloid-derived suppressor cells (Mo-MDSC), and interleukin-6 (IL-6) responses were measured before and at the eighth vaccination. Clinical outcomes were also analyzed. Combination therapy of PPV with HM was well tolerated without severe adverse events. There was no significant change in antigen-specific IgG, CTL, Treg or clinical outcomes. Combination therapy of PPV with HM stabilized the frequency of Mo-MDSC (1.91%-1.92%, P = 0.96) and serum levels of IL-6 (19.2 pg/mL to 16.1 pg/mL, P = 0.63) during the treatment. In contrast, the frequency of Mo-MDSC and levels of IL-6 in the PPV-alone group were significantly increased (0.91%-1.49% for Mo-MDSC and 9.2 pg/mL to 19.4 pg/mL for IL-6, respectively). These results suggest that the combined use of HM has the potential to prevent the immunosuppression induced by Mo-MDSC or IL-6 during immunotherapy. More research is needed to validate the findings of the present study.

SUBMITTER: Koga N

PROVIDER: S-EPMC5715291 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Immunological efficacy of herbal medicines in prostate cancer patients treated by personalized peptide vaccine.

Koga Noriko N Moriya Fukuko F Waki Kayoko K Yamada Akira A Itoh Kyogo K Noguchi Masanori M

Cancer science 20171003 12

This randomized phase II study investigated the immunological efficacy of herbal medicines (HM) using Hochu-ekki-to and Keishi-bukuryo-gan in combination with personalized peptide vaccination (PPV) for castration-resistant prostate cancer (CRPC). Seventy patients with CRPC were assigned to two arms; PPV plus HM or PPV alone. Two to four peptides were chosen from 31 peptides derived from cancer antigens for a s.c. injection of PPV given eight times according to the patient's human leukocyte antig ...[more]

PMID: 28898532

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Project description:Hochuekkito (HET), Juzentaihoto (JTT), and Ninjin'yoeito (NYT) have been used as Hozai, a group of traditional Japanese herbal medicines, to treat physically and mentally weak cancer patients. Their compositions are quite different, and Japanese pharmaceutical companies have been using different types or quantities of herbs for formulations with the same name. Here, we compared the immunological differences between HET, JTT, and NYT with respect to the induced T cell subsets and cytokines. Peripheral blood mononuclear cells (PBMCs) were isolated from healthy volunteers and treated with 0 (control), 25, 50, 100, 200, or 400 μg/mL HET, JTT, or NYT (manufactured by Tsumura [TJ], Kracie [KR], and Kotaro [KO]). PBMC proliferation, CD4+ T cell, CD8+ T cell, and regulatory T cell (Treg) proportions and interleukin (IL) concentrations (IL-6, IL-10, IL-17A, interferon-γ, tumor necrosis factor-α, and transforming growth factor (TGF)-β) secreted by PBMCs were measured using Cell Counting Kit-8 or flow cytometry bead analysis. PBMC proliferation and CD4+ T cell percentages were similar in the HET, JTT, NYT, and control groups; however, the percentage of CD8+ T cells tended to increase after treatments. Tregs were suppressed by HET, JTT, and NYT, and TJ-JTT significantly decreased Treg numbers (compared with control). The concentrations of all cytokines except TGF-β were increased in a concentration-dependent manner (p < 0.05); particularly, KR-HET induced IL-6 secretion (compared with the control, TJ-HET, and KO-HET; 37-, 7-, and 17-fold, respectively; p < 0.05). The TGF-β concentration was decreased in a concentration-dependent manner by HET, JTT, and NYT (compared with the control). These results suggest that, compared with TJ-HET and KO-HET, KR-HET should be administered with caution. Although HET, JTT, and NYT belong to the same Hozai group and have the same names among companies, their differing effects on immune activity must be considered and they must be administered with caution.

Project description:BACKGROUND:Hypercholesterolemia is an important key contributory factor for ischemic heart disease and is associated with age, high blood pressure, a family history of hypercholesterolemia, and diabetes. Chinese herbal medicines have been used for a long time as lipid-lowering agents. OBJECTIVES:To assess the effects of Chinese herbal medicines on hypercholesterolemia. SEARCH STRATEGY:We searched the following databases: The Cochrane Library (issue 8, 2010), MEDLINE (until July 2010), EMBASE (until July 2010 ), Chinese BioMedical Database (until July 2010), Traditional Chinese Medical Literature Analysis and Retrieval System (until July 2010), China National Knowledge Infrastructure (until July 2010), Chinese VIP Information (until July 2010), Chinese Academic Conference Papers Database and Chinese Dissertation Database (until July 2010), and Allied and Complementary Medicine Database (until July 2010). SELECTION CRITERIA:We considered randomized controlled clinical trials in hypercholesterolemic participants comparing Chinese herbal medicines with placebo, no treatment, and pharmacological or non-pharmacological interventions. DATA COLLECTION AND ANALYSIS:Two review authors independently extracted data and assessed the risk of bias. We resolved any disagreements with this assessment through discussion and a decision was achieved based by consensus. We assessed trials for the risk of bias against key criteria: random sequence generation, allocation concealment, blinding of participants, incomplete outcome data, selective outcome reporting and other sources of bias. MAIN RESULTS:We included 22 randomized trials (2130 participants). The mean treatment duration was 2.3 ± 1.3 months (ranging from one to six months). Twenty trials were conducted in China and 18 trials were published in Chinese. Overall, the risk of bias of included trials was high or unclear. Five different herbal medicines were evaluated in the included trials, which compared herbs with conventional medicine in six comparisons (20 trials), or placebo (two trials). There were no outcome data in any of the trials on cardiovascular events and death from any cause. One trial each reported well-being (no significant differences) and economic costs. No serious adverse events were observed. Xuezhikang was the most commonly used herbal formula investigated. A significant effect on total cholesterol (two trial, 254 participants) was shown in favor of Xuezhikang when compared with inositol nicotinate (mean difference (MD) -0.90 mmol/L, 95% confidence interval (CI) -1.13 to -0.68) . AUTHORS' CONCLUSIONS:Some herbal medicines may have cholesterol-lowering effects. Our findings have to be interpreted with caution due to high or unclear risk of bias of the included trials.

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Immunological efficacy of herbal medicines in prostate cancer patients treated by personalized peptide vaccine.

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Immunological efficacy of herbal medicines in prostate cancer patients treated by personalized peptide vaccine.

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