溶瘤病毒药物的研究进展

doi:10.19803/j.1672-8629.20220222

摘要/Abstract

摘要： 目的进一步了解溶瘤病毒及其药物,为后续溶瘤病毒药物安全性评价提供参考。方法总结并分析近年来关于溶瘤病毒作用机制、相关药物临床研究及其联合疗法的研究进展。结果目前共有Rigvir（ECHO-7病毒）、安柯瑞（重组人5型腺病毒）、T-Vec（单纯疱疹病毒）、Delytact（单纯疱疹病毒）4款溶瘤病毒类药物上市,均具有良好的疗效。并且随着生物技术的发展,溶瘤病毒制备策略更加多样有效。结论溶瘤病毒疗法具有杀伤效率高、靶向性好、不良反应小、多种杀伤肿瘤途径避免耐药性和成本低廉等诸多优点,有望成为新型肿瘤治疗策略。

关键词: 溶瘤痘苗病毒, 溶瘤疱疹病毒, 溶瘤腺病毒, RNA溶瘤病毒, 联合疗法

Abstract: Objective To find out more about the oncolytic virus and related drugs so as to provide reference for subsequent safety evaluation of oncolytic drugs. Methods The research progress in the mechanism of oncolytic virus, clinical research of related drugs and their combination therapy in recent years were summarized and analyzed. Results There were four oncolytic viral drugs on the market, all of which had good curative effects. With the development of biotechnology, preparation strategies of oncolytic virus became more diverse and effective. Conclusion Oncolytic viral therapy has many advantages, such as high killing efficiency, good targeting, low adverse reactions, multiple ways to kill tumors, little drug resistance and low cost. It is expected to become a new tumor treatment strategy.

Key words: oncolytic pox vaccine virus, oncolytic herpes virus, oncolytic adenovirus, RNA oncolytic virus, combination therapy

中图分类号:

R979.1

周鹏博, 周晓冰, 黄瑛, 耿兴超. 溶瘤病毒药物的研究进展[J]. 中国药物警戒, 2023, 20(1): 7-11.

ZHOU Pengbo, ZHOU Xiaobing, HUANG Ying, GENG Xingchao. Research progress in oncolytic drugs[J]. Chinese Journal of Pharmacovigilance, 2023, 20(1): 7-11.

参考文献

[1] SUNG H, FERLAY J, SIEGEL RL, et al.Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249.
[2] MALIK D, MAHENDIRATTA S, KAUR H, et al.Futuristic approach to cancer treatment[J]. Gene, 2021, 805: 145906.
[3] DEPIL S, DUCHATEAU P, GRUPP SA, et al.Off-the-shelf allogeneic CAR T cells: development and challenges[J]. Nat Rev Drug Discov, 2020, 19(3): 185-199.
[4] WANG X, MIAO YF, HUO Y, et al.Reflections on the non-clinical safety evaluation of oncolytic virus drugs[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2021, 18(6): 597-600.
[5] GUO ZS, LU B, GUO Z, et al.Vaccinia virus-mediated cancer immunotherapy: cancer vaccines and oncolytics[J]. J Immunother Cancer, 2019, 7(1): 6.
[6] KIM M, NITSCHKE M, SENNINO B, et al.Amplification of oncolytic vaccinia virus widespread tumor cell killing by sunitinib through multiple mechanisms[J]. Cancer Res, 2018, 78(4): 922-937.
[7] HUANG YH, LU YY, XIE Z, et al.Research progress of oncolytic virus in tumor treatment[J]. Infectious Disease Information(传染病信息), 2019, 32(1): 30-36.
[8] STREBY KA, GELLER JI, CURRIER MA, et al.Intratumoral injection of HSV1716, an oncolytic herpes virus, is safe and shows evidence of immune response and viral replication in young cancer patients[J]. Clin Cancer Res, 2017, 23(14): 3566-3574.
[9] PARATO KA, BREITBACH CJ, LE BOEUF F, et al.The oncolytic poxvirus JX-594 selectively replicates in and destroys cancer cells driven by genetic pathways commonly activated in cancers[J]. Mol Ther, 2012, 20(4): 749-758.
[10] DENG L, FAN J, DING Y, et al.Oncolytic efficacy of thymidine kinase-deleted vaccinia virus strain Guang9[J]. Oncotarget, 2017, 8(25): 40533-40543.
[11] SUN BQ, WANG QY, PAN LD.Advances in the study of the latent and activation mechanisms of herpes simplex virus[J]. Journal of Zhejiang University (Medical Edition) [浙江大学学报(医学版)], 2019, 48(1): 89-101.
[12] UCHE IK, KOUSOULAS KG, RIDER PJF.The effect of herpes simplex virus-type-1 (HSV-1) oncolytic immunotherapy on the tumor microenvironment[J]. Viruses, 2021, 13(7): 1200.
[13] CUI J, WEI W.General considerations of the research status of oncolytic herpes simplex virus type 1 and its pharmacological evaluation[J]. Advances in Microbiology and Immunology(微生物学免疫学进展), 2021, 49(4): 66-73.
[14] FERRUCCI PF, PALA L, CONFORTI F, et al.Talimogene laherparepvec (T-VEC): an intralesional cancer immunotherapy for advanced melanoma[J]. Cancers (Basel), 2021, 13(6): 1383.
[15] BROMAN KK, ZAGER JS.An evaluation of talimogene laherparepvec for the treatment of melanoma[J]. Expert Opin Biol Ther, 2020, 20(1): 9-14.
[16] LAROCCA CA, LEBOEUF NR, SILK AW, et al.An update on the role of talimogene laherparepvec (T-VEC) in the treatment of melanoma: best practices and future directions[J]. Am J Clin Dermatol, 2020, 21(6): 821-832.
[17] SUNDARESAN P, HUNTER WD, MARTUZA RL, et al.Attenuated, replication-competent herpes simplex virus type 1 mutant G207: safety evaluation in mice[J]. J Virol, 2000, 74(8): 3832-3841.
[18] FUKUHARA H, TAKESHIMA Y, TODO T.Triple-mutated oncolytic herpes virus for treating both fast- and slow-growing tumors[J]. Cancer Sci, 2021, 112(8): 3293-3301.
[19] ZHAO Q, ZHANG W, NING Z, et al.A novel oncolytic herpes simplex virus type 2 has potent anti-tumor activity[J]. PLoS One, 2014, 9(3): e93103.
[20] WANG Y, ZHOU X, WU Z, et al.Preclinical safety evaluation of oncolytic herpes simplex virus type 2[J]. Hum Gene Ther, 2019, 30(5): 651-660.
[21] SUN T, HE XL.Research advances in tumor-targeting adenovirus preparation strategies[J]. Chinese Journal of Oncology Biotherapy(中国肿瘤生物杂志), 2018, 25(2): 198-205.
[22] NIEMANN J, KUHNEL F.Oncolytic viruses: adenoviruses[J]. Virus Genes, 2017, 53(5): 700-706.
[23] CERVERA-CARRASCON V, HAVUNEN R, HEMMINKI A.Oncolytic adenoviruses: a game changer approach in the battle between cancer and the immune system[J]. Expert Opin Biol Ther, 2019, 19(5): 443-455.
[24] MANTWILL K, KLEIN FG, WANG D, et al.Concepts in oncolytic adenovirus therapy[J]. Int J Mol Sci, 2021, 22(19): 10522.
[25] ZHAO Y, LIU Z, LI L, et al.Oncolytic adenovirus: prospects for cancer immunotherapy[J]. Front Microbiol, 2021, 12: 707290.
[26] HEMMINKI O, PARVIAINEN S, JUHILA J, et al.Immunological data from cancer patients treated with Ad5/3-E2F-Delta24-GMCSF suggests utility for tumor immunotherapy[J]. Oncotarget, 2015, 6(6): 4467-4481.
[27] TAZAWA H, HASEI J, YANO S, et al.Bone and soft-tissue sarcoma: a new target for telomerase-specific oncolytic virotherapy[J]. Cancers (Basel), 2020, 12(2): 478.
[28] YAMASAKI Y, TAZAWA H, HASHIMOTO Y, et al.A novel apoptotic mechanism of genetically engineered adenovirus-mediated tumour-specific p53 overexpression through E1A-dependent p21 and MDM2 suppression[J]. Eur J Cancer, 2012, 48(14): 2282-2291.
[29] YANO S, TAKEHARA K, MIWA S, et al.Fluorescence-guided surgery of a highly-metastatic variant of human triple-negative breast cancer targeted with a cancer-specific GFP adenovirus prevents recurrence[J]. Oncotarget, 2016, 7(46): 75635-75647.
[30] SIMON EJ, HOWELLS MA, STUART JD, et al.Serotype-specific killing of large cell carcinoma cells by reovirus[J]. Viruses, 2017, 9(6):140.
[31] MACEDO N, MILLER D M, HAQ R, et al.Clinical landscape of oncolytic virus research in 2020[J]. J Immunother Cancer, 2020, 8(2): e001486.
[32] VIJAYAKUMAR G, MCCROSKERY S, PALESE P.Engineering newcastle disease virus as an oncolytic vector for intratumoral delivery of immune checkpoint inhibitors and immunocytokines[J]. J Virol, 2020, 94(3): e01677-e01719.
[33] SUI H, WANG K, XIE R, et al.NDV-D90 suppresses growth of gastric cancer and cancer-related vascularization[J]. Oncotarget, 2017, 8(21): 34516-34524.
[34] BOURGEOIS-DAIGNEAULT MC, ROY DG, AITKEN AS, et al. Neoadjuvant oncolytic virotherapy before surgery sensitizes triple-negative breast cancer to immune checkpoint therapy[J]. Sci Transl Med, 2018, 10(422): eaao1641.
[35] LIU Z, RAVINDRANATHAN R, KALINSKI P, et al.Rational combination of oncolytic vaccinia virus and PD-L1 blockade works synergistically to enhance therapeutic efficacy[J]. Nat Commun, 2017, 8: 14754.
[36] ROULSTONE V, PEDERSEN M, KYULA J, et al.BRAF- and MEK-Targeted small molecule inhibitors exert enhanced antimelanoma effects in combination with oncolytic reovirus through ER stress[J]. Mol Ther, 2015, 23(5): 931-942.
[37] LI YJ, LEI W, QIN Y, et al.Discussion on the inhibitory effect and mechanism of sorafenib combined with tumorolytic pox seedling virus on liver cancer cells[J]. Journal of Central China Normal University (Natural Science Edition) [华中师范大学学报(自然科学版)], 2017, 51(5): 638-645.
[38] PARK A K, FONG Y, KIM S I, et al. Effective combination immunotherapy using oncolytic viruses to deliver CAR targets to solid tumors[J]. Sci Transl Med, 2020, 12(559): eaaz1863.