溶瘤单纯疱疹病毒抗肿瘤作用及其机理研究
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摘要
目前,已有溶瘤病毒在临床治疗上应用,是一种有效的癌症免疫治疗方法。近年来研究人员对单纯疱疹病毒的研究越来越广泛,尤其是Ⅰ型单纯疱疹病毒。为了探索溶瘤单纯疱疹病毒抗肿瘤作用及其机理,从单纯疱疹病毒的生物学特点,溶瘤单纯疱疹病毒的抗肿瘤机制,溶瘤单纯疱疹病毒的临床应用及其局限性等方面进行归纳整理。研究表明,溶瘤病毒通过多步法包括直接裂解肿瘤细胞,诱导细胞毒性或凋亡致敏细胞因子以及促进抗肿瘤T细胞应答来达到抗肿瘤的作用。增强溶瘤治疗期间的免疫反应可增强其抗肿瘤效果。溶瘤病毒在肿瘤治疗方面已经成为一种新兴制剂。
Currently, some oncolytic viruses(OV) have been used in clinical treatment as an effective cancer immunotherapy. In recent years, there have been increasing studies on herpes simplex virus(HSV) in various aspects, especially HSV type I. To explore the anti-tumor effect of herpes simplex virus and its mechanism, this article summarizes the biological characteristics, the anti-tumor mechanism, the clinical application and limitations of HSV. The results show that therapy using OV is an effective immunotherapeutic approach for cancer treatment by a multistep process including direct tumor cell lysis, induction of cytotoxicity, or apoptosis-sensitive cytokines, and promotion of antitumor T cell responses. Enhanced immune response during oncolytic therapy may enhance its anti-tumor effect. OV has been a new agent of cancer treatment.
Currently, some oncolytic viruses(OV) have been used in clinical treatment as an effective cancer immunotherapy. In recent years, there have been increasing studies on herpes simplex virus(HSV) in various aspects, especially HSV type I. To explore the anti-tumor effect of herpes simplex virus and its mechanism, this article summarizes the biological characteristics, the anti-tumor mechanism, the clinical application and limitations of HSV. The results show that therapy using OV is an effective immunotherapeutic approach for cancer treatment by a multistep process including direct tumor cell lysis, induction of cytotoxicity, or apoptosis-sensitive cytokines, and promotion of antitumor T cell responses. Enhanced immune response during oncolytic therapy may enhance its anti-tumor effect. OV has been a new agent of cancer treatment.
引文
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[26] GHONIME M G,JACKSON J,SHAH A,et al.Chimeric HCMV/HSV-1 and Δγ134.5 oncolyticherpes simplex virus elicit immune mediated antigliomal effect and antitumor memory[J].Translational Oncology,2018,11(1):86.
[2] JOHNSON D B,PUZANOV I,KELLEY M C.Talimogene laherparepvec (T-VEC) for the treatment of advanced melanoma[J].Immunotherapy,2015,7(6):611-619.
[3] CONRADY C D,DREVETS D A,CARR D J J.Herpes Simplex Type I (HSV-1) Infection of the Nervous System:Is an Immune Response a Good Thing?[J].Journal of Neuroimmunology,2010,220(1):1-9.
[4] EAGER RM,NEMUNAITIS J.Clinical development directions in oncolytic viral therapy[J].Cancer Gene Therapy,2011,18(5):305-317.
[5] CHOU J,KERN ER,WHITLEY RJ,et al.Mapping of herpes simplex virus-1 neurovirulence to gamma 134.5,a gene nonessential for growth in culture[J].Science,1990,250(4 985):1 262-1 266.
[6] WALKER J D,SEHGAL I,KOUSOULAS K G.Oncolytic Herpes Simplex Virus 1 Encoding 15-Prostaglandin Dehydrogenase Mitigates Immune Suppression and Reduces Ectopic Primary and Metastatic Breast Cancer in Mice[J].Journal of Virology,2011,85(14):7 363.
[7] COEN D M,KOSZVNENCHAK M,JACOBSON J G,et al.Thymidine kinase-negative herpes simplex virus mutants establish latency in mouse trigeminal ganglia but do not reactivate[J].Proceedings of the National Academy of Sciences of the United States of America,1989,86(12):4 736-4 740.
[8] MARKERT J M,MALICK A,COEN D M,et al.Reduction and elimination of encephalitis in an experimental glioma therapy model with attenuated herpes simplex mutants that retain susceptibility to acyclovir[J].Neurosurgery,1993,32(4):597-603.
[9] SHIROTA T,KASUYA H,KODERA Y,et al.Oncolytic herpes virus induces effective anti-cancer immunity against murine colon cancer[J].Hepato-gastroenter ology 2011,58(110-111):1 482-1 489.
[10] WATANABE I,KASUYA H,NOMURA N,et al.Effects of tumor selective replication-competent herpes viruses in combination with gemcitabine on pancreatic cancer[J].Cancer Chemotherapy & Pharmacology,2008,61(5):875.
[11] KANZAKI A,KASUYA H,YAMAMURA K,et al.Antitumor efficacy of oncolytic herpes simplex virus adsorbed onto antigen-specific lymphocytes[J].Cancer Gene Therapy,2012,19(4):292.
[12] LORET S,GUAY G,LIPPé R.Comprehensive characterization of extracellular herpes simplex virus type 1 virions[J].Journal of Virology,2008,82(17):8 605-8 618.
[13] KOSHIZUKA T,KAWAGUCHI Y,NISHIYAMA Y.Herpes simplex virus type 2 membrane protein UL56 associates with the kinesin motor protein KIF1A[J].Journal of General Virology,2005,86(3):527-533.
[14] KROEGER K M,MUHAMMAD A K,BAKER G J,et al.Gene therapy and virotherapy:novel therapeutic approaches for brain tumors[J].Discovery Medicine,2010,10(53):293-304.
[15] TODO T."Armed" oncolytic herpes simplex viruses for brain tumor therapy[J].Cell Adh Migr,2008,2(3):208-213.
[16] WANG J N,HU P,ZENG M S,et al.Anti-tumor effect of oncolytic herpes simplex virus G47delta on human nasopharyngeal carcinoma[J].Chinese Journal of Cancer,2011,30(12):831-841.
[17] RYUICHI KANAI,HIROAKI WAKIMOTO,TOOBA CHEEMA,et al.Oncolytic herpes simplex virus vectors and chemotherapy:are combinatorial strategies more effective for cancer?[J].Future Oncology,2010,6(4):619-634.
[18] SAHIN T T,KASUYA H,NOMURA N,et al.Impact of novel oncolytic virus HF10 on cellular components of the tumor microenviroment in patients with recurrent breast cancer[J].Cancer Gene Therapy,2012,19(4):229-237.
[19] KAUFMAN H L,KIM D W,DERAFFELE G,et al.Local and distant immunity induced by intralesional vaccination with an oncolytic herpes virus encoding GM-CSF in patients with stage IIIc and IV melanoma[J].Annals of Surgical Oncology,2010,17(3):718.
[20] ANDTBACKA R H,KAUFMAN H L,COLLICHIO F,et al.Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma[J].Journal of Clinical Oncology,2015,33(25):2 780-2 788.
[21] JAIN RK.Normalization of tumor vasculature:an emerging concept in antiangiogenic therapy[J].Science,2005,307(5 706):58-62.
[22] OTTOLINOPERRY K,DIALLO J S,LICHTY B D,et al.Intelligent Design:Combination Therapy With Oncolytic Viruses[J].Molecular Therapy the Journal of the American Society of Gene Therapy,2010,18(2):251.
[23] CHEN C Y,WANG P Y,HUTZEN B,et al.Cooperation of Oncolytic Herpes Virotherapy and PD-1 Blockade in Murine Rhabdomyosarcoma Models[J].Sci Rep,2017,7(1):2 396.
[24] Jaime Ramirez A C,Dmitrieva N,Yoo J Y,et al.Humanized chondroitinase ABC sensitizes glioblastoma cells to temozolomide[J].Journal of Gene Medicine,2017,19(3):e 2 942.
[25] JAHAN N,LEE J M,SHAH K,et al.Therapeutic targeting of chemoresistant and recurrent glioblastoma stem cells with a proapoptotic variant of oncolytic herpes simplex virus[J].International Journal of Cancer,2017,141(8):1 671-1 681.
[26] GHONIME M G,JACKSON J,SHAH A,et al.Chimeric HCMV/HSV-1 and Δγ134.5 oncolyticherpes simplex virus elicit immune mediated antigliomal effect and antitumor memory[J].Translational Oncology,2018,11(1):86.