Koga Noriko, Moriya Fukuko, Waki Kayoko, Yamada Akira, Itoh Kyogo, Noguchi Masanori
Division of Clinical Research, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan.
Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
Cancer Sci. 2017 Dec;108(12):2326-2332. doi: 10.1111/cas.13397. Epub 2017 Oct 3.
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.
这项随机II期研究调查了使用补中益气汤和桂枝茯苓丸联合个性化肽疫苗接种（PPV）治疗去势抵抗性前列腺癌（CRPC）的草药（HM）的免疫疗效。70例CRPC患者被分为两组；PPV加HM组或单独PPV组。从31种源自癌症抗原的肽中选择2至4种肽，根据患者的人类白细胞抗原类型和PPV治疗前抗原特异性IgG滴度水平，皮下注射PPV，共注射8次。在第8次接种前和接种时测量肽特异性CTL、IgG、调节性T细胞（Treg）、单核细胞来源的髓系抑制细胞（Mo-MDSC）和白细胞介素-6（IL-6）反应。还分析了临床结果。PPV与HM的联合治疗耐受性良好，无严重不良事件。抗原特异性IgG、CTL、Treg或临床结果无显著变化。PPV与HM的联合治疗在治疗期间使Mo-MDSC的频率稳定（1.91%-1.92%，P = 0.96）和IL-6的血清水平稳定（19.2 pg/mL至16.1 pg/mL，P = 0.63）。相比之下，单独PPV组的Mo-MDSC频率和IL-6水平显著增加（Mo-MDSC分别为0.91%-1.49%，IL-6为9.2 pg/mL至19.4 pg/mL）。这些结果表明，HM的联合使用有可能预防免疫治疗期间由Mo-MDSC或IL-6诱导的免疫抑制。需要更多的研究来验证本研究的结果。
