中国新药杂志

个体化肽治疗性肿瘤疫苗的临床药效学研究分析

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贺庆 , 高华 , 王军志

中国新药杂志 | 生物医药前沿 2021,30(19): 1729-1737

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中国新药杂志 |生物医药前沿 2021 , 30 (19) : 1729 -1737

个体化肽治疗性肿瘤疫苗的临床药效学研究分析

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贺庆, 高华, 王军志

作者信息

中国食品药品检定研究院创新疫苗及生物技术产品评价与标准化国家重点实验室，北京　102629

通讯作者:

王军志，男，博士，研究员，博士生导师，主要从事生物制品的质量控制与标准化研究。联系电话：（010）53851527，E-mail：wangjz@nifdc.org.cn。

作者简介:

贺庆，男，博士，研究员，主要从事生物制品的药效学与质量评价。联系电话：（010）53851580，E-mail：heqing@nifdc.org.cn。

Clinical pharmacodynamics analysis of personalized peptide therapeutic tumor vaccines

Qing HE, Hua GAO, Jun-zhi WANG

Affiliations

National Institutes for Food and Drug Control, State Key Laboratory for Evaluation and Standardization of Innovative Vaccines and Biotechnology Products, Beijing 102629, China

出版时间: 2021-10-15

文章导航

摘要

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个体化肽治疗性肿瘤疫苗是根据患者肿瘤异质性和人白细胞抗原异质性制备的一种精准医疗产品，具有抑瘤作用特异性强、不良反应少、抗原序列明确、易于制备和质控、经济成本相对较低等特点，此类疫苗已成为研发肿瘤疫苗的热点。本文分析总结了近20年来个体化肿瘤相关抗原肽和个体化肿瘤新抗原肽治疗性肿瘤疫苗的Ⅰ~Ⅲ期临床药效学研究概况，以期为进行此类疫苗的研发和评价提供参考。目前，临床患者对个体化肿瘤相关抗原肽治疗性肿瘤疫苗产生特异性体液和细胞免疫反应率分别约为70%和60%，个体化肿瘤新抗原肽治疗性肿瘤疫苗中约60%的新抗原可诱导患者产生特异性细胞免疫反应，这2类疫苗最常见的不良反应为注射部位皮肤反应，整体具有较好的免疫原性和耐受性。

关键词

个体化治疗性肿瘤疫苗 / 肽疫苗 / 临床药效学 / 肿瘤相关抗原 / 肿瘤新抗原

Abstract

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Personalized peptide therapeutic tumor vaccine is a kind of precision medical product prepared according to the tumor heterogeneity and human leukocyte antigen heterogeneity in patients. It has strong anti-tumor specificity, low toxic and side effects, definite antigen sequence, and is easy to be prepared and controlled. Additionally, the economic cost is relatively low. This kind of vaccine has become a hot spot in tumor vaccine development. This paper analyzes and summarizes the Ⅰ~Ⅲ phase clinical pharmacodynamics researches of personalized tumor-associated antigen peptide therapeutic tumor vaccines and personalized tumor neoantigen peptide therapeutic tumor vaccines in the recent 2 decades, in order to provide a reference for the development and evaluation of such vaccines. At present, the specific humoral and cellular immune response rates of patients vaccinated with personalized tumor-associated peptide therapeutic tumor vaccines are about 70% and 60%, respectively. The specific cellular immune response can be induced in patients by about 60% of the neoantigens in personalized tumor neoantigen peptide therapeutic tumor vaccines. The most common adverse reaction of the two types of vaccines was skin reaction at the injection site, both of which generally had good immunogenicity and tolerability.

Key words

personalized therapeutic cancer vaccine / peptide vaccine / clinical pharmacodynamics / tumor-associated antigen / tumor neoantigen

引用本文

贺庆, 高华, 王军志. 个体化肽治疗性肿瘤疫苗的临床药效学研究分析. 中国新药杂志, 2021 , 30 (19) : 1729 -1737 .

Qing HE, Hua GAO, Jun-zhi WANG. Clinical pharmacodynamics analysis of personalized peptide therapeutic tumor vaccines[J]. Chinese Journal of New Drugs, 2021 , 30 (19) : 1729 -1737 .

基金

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国家“重大新药创制”科技重大专项资助项目(2018ZX09101-001)
创新生物技术药评价及标准化关键技术研究

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排序方式：

[1]

SOLINAS C, AIELLO M, MIGLIORI E, et al. Breast cancer vaccines: heeding the lessons of the past to guide a path forward[J]. Cancer Treat Rev, 2020, 84: 101947.

[2]

HE Q, GAO H, GAO M, et al. Anti-gastrins antiserum combined with lowered dosage cytotoxic drugs to inhibit the growth of human gastric cancer SGC7901 cells in nude mice[J]. J Cancer, 2015, 6(5): 448-456.

[3]

HE Q, GAO H, GAO M, et al. Immunogenicity and safety of a novel tetanus toxoid-conjugated anti-gastrin vaccine in BALB/c mice[J]. Vaccine, 2018, 36(6): 847-852.

[4]

KWAK M, LEICK KM, MELSSEN MM, et al. Vaccine strategy in melanoma[J]. Surg Oncol Clin N Am, 2019, 28(3): 337-351.

[5]

KORDALIVAND N, TONDINI E, LAU CYJ, et al. Cationic synthetic long peptides-loaded nanogels: An efficient therapeutic vaccine formulation for induction of T-cell responses[J]. J Control Release, 2019, 315: 114-125.

[6]

SONG Q, ZHANG CD, WU XH. Therapeutic cancer vaccines: From initial findings to prospects[J]. Immunol Lett, 2018, 196: 11-21.

[7]

NOGUCHI M, ITOH K, SUEKANE S, et al. Phase I trial of patient-oriented vaccination in HLA-A2-positive patients with metastatic hormone-refractory prostate cancer[J]. Cancer Sci, 2004, 95(1): 77-84.

[8]

NOGUCHI M, YAO A, HARADA M, et al. Immunological evaluation of neoadjuvant peptide vaccination before radical prostatectomy for patients with localized prostate cancer[J]. Prostate, 2007, 67(9): 933-942.

[9]

SATO Y, FUJIWARA T, MINE T, et al. Immunological evaluation of personalized peptide vaccination in combination with a 5-fluorouracil derivative (TS-1) for advanced gastric or colorectal carcinoma patients[J]. Cancer Sci, 2007, 98(7): 1113-1119.

[10]

NAITO M, ITOH K, KOMATSU N, et al. Dexamethasone did not suppress immune boosting by personalized peptide vaccination for advanced prostate cancer patients[J]. Prostate, 2008, 68(16): 1753-1762.

[11]

HATTORI T, MINE T, KOMATSU N, et al. Immunological evaluation of personalized peptide vaccination in combination with UFT and UZEL for metastatic colorectal carcinoma patients[J]. Cancer Immunol Immunother, 2009, 58(11): 1843-1852.

[12]

UEMURA H, FUJIMOTO K, MINE T, et al. Immunological evaluation of personalized peptide vaccination monotherapy in patients with castration-resistant prostate cancer[J]. Cancer Sci, 2010, 101(3): 601-608.

[13]

MATSUMOTO K, NOGUCHI M, SATOH T, et al. A phase Ⅰ study of personalized peptide vaccination for advanced urothelial carcinoma patients who failed treatment with methotrexate, vinblastine, adriamycin and cisplatin[J]. BJU Int, 2011, 108(6): 831-838.

[14]

NOGUCHI M, UEMURA H, NAITO S, et al. A phase Ⅰ study of personalized peptide vaccination using 14 kinds of vaccine in combination with low-dose estramustine in HLA-A24-positive patients with castration-resistant prostate cancer[J]. Prostate, 2011, 71(5): 470-479.

[15]

TERASAKI M, SHIBUI S, NARITA Y, et al. Phase I trial of a personalized peptide vaccine for patients positive for human leukocyte antigen——A24 with recurrent or progressive glioblastoma multiforme[J]. J Clin Oncol, 2011, 29(3): 337-344.

[16]

YOSHIYAMA K, TERAZAKI Y, MATSUEDA S, et al. Personalized peptide vaccination in patients with refractory non-small cell lung cancer[J]. Int J Oncol, 2012, 40(5): 1492-1500.

[17]

NOGUCHI M, MORIYA F, SUEKANE S, et al. Phase II study of personalized peptide vaccination for castration-resistant prostate cancer patients who failed in docetaxel-based chemotherapy[J]. Prostate, 2012, 72(8): 834-845.

[18]

YUTANI S, KOMATSU N, MATSUEDA S, et al. Juzentaihoto failed to augment antigen-specific immunity but prevented deterioration of patients' conditions in advanced pancreatic cancer under personalized peptide vaccine[J]. Evid Based Complement Alternat Med, 2013, 2013: 981717.

[19]

KIBE S, YUTANI S, MOTOYAMA S, et al. Phase II study of personalized peptide vaccination for previously treated advanced colorectal cancer[J]. Cancer Immunol Res, 2014, 2(12): 1154-1162.

[20]

NOGUCHI M, MATSUMOTO K, UEMURA H, et al. An open-label, randomized phase Ⅱ trial of personalized peptide vaccination in patients with bladder cancer that progressed after platinum-based chemotherapy[J]. Clin Cancer Res, 2016, 22(1): 54-60.

[21]

YOSHIMURA K, MINAMI T, NOZAWA M, et al. A phase 2 randomized controlled trial of personalized peptide vaccine immunotherapy with low-dose dexamethasone versus dexamethasone alone in chemotherapy-naive castration-resistant prostate cancer[J]. Eur Urol, 2016, 70(1): 35-41.

[22]

NOGUCHI M, MORIYA F, KOGA N, et al. A randomized phase Ⅱ clinical trial of personalized peptide vaccination with metronomic low-dose cyclophosphamide in patients with metastatic castration-resistant prostate cancer[J]. Cancer Immunol Immunother, 2016, 65(2): 151-160.

[23]

SHIRAHAMA T, MUROYA D, MATSUEDA S, et al. A randomized phase Ⅱ trial of personalized peptide vaccine with low dose cyclophosphamide in biliary tract cancer[J]. Cancer Sci, 2017, 108(5): 838-845.

[24]

KOGA N, MORIYA F, WAKI K, et al. Immunological efficacy of herbal medicines in prostate cancer patients treated by personalized peptide vaccine[J]. Cancer Sci, 2017, 108(12): 2326-2332.

[25]

NOGUCHI M, FUJIMOTO K, ARAI G, et al. A randomized phase Ⅲ trial of personalized peptide vaccination for castration-resistant prostate cancer progressing after docetaxel[J]. Oncol Rep, 2021, 45(1): 159-168.

[26]

OTT PA, HU Z, KESKIN DB, et al. An immunogenic personal neoantigen vaccine for patients with melanoma[J]. Nature, 2017, 547(7662): 217-221.

[27]

JOHANNS TM, MILLER CA, LIU CJ, et al. Detection of neoantigen-specific T cells following a personalized vaccine in a patient with glioblastoma[J]. Oncoimmunology, 2019, 8(4): e1561106.

[28]

HILF N, KUTTRUFF-COQUI S, FRENZEL K, et al. Actively personalized vaccination trial for newly diagnosed glioblastoma [published correction appears in Nature. 2019 Feb;566(7745): E13][J]. Nature, 2019, 565(7738): 240-245.

[29]

KESKIN DB, ANANDAPPA AJ, SUN J, et al. Neoantigen vaccine generates intratumoral T cell responses in phase Ⅰb glioblastoma trial[J]. Nature, 2019, 565(7738): 234-239.

[30]

OTT PA, HU-LIESKOVAN S, CHMIELOWSKI B, et al. A phase Ⅰb trial of personalized neoantigen therapy plus anti-PD-1 in patients with advanced melanoma, non-small cell lung cancer, or bladder cancer[J]. Cell, 2020, 183(2): 347-362.

[31]

FANG Y, MO F, SHOU J, et al. A pan-cancer clinical study of personalized neoantigen vaccine monotherapy in treating patients with various types of advanced solid tumors[J]. Clin Cancer Res, 2020, 26(17): 4511-4520.

2021年第30卷第19期

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首发时间：2026-10-30
出版时间：2021-10-15

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录用日期：2021-05-03

基金

国家“重大新药创制”科技重大专项资助项目(2018ZX09101-001)

创新生物技术药评价及标准化关键技术研究

作者信息

中国食品药品检定研究院创新疫苗及生物技术产品评价与标准化国家重点实验室，北京　102629

通讯作者:

王军志，男，博士，研究员，博士生导师，主要从事生物制品的质量控制与标准化研究。联系电话：（010）53851527，E-mail：wangjz@nifdc.org.cn。

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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