
浏览全部资源
扫码关注微信
1. 上海交通大学医学院附属胸科医院上海市肺部肿瘤临床医学中心,上海 200030
2. 复旦大学附属肿瘤医院肿瘤内科,复旦大学上海医学院肿瘤学系,上海 200032
[ "梁滢昀(ORCID: 0009-0001-9061-158X),博士在读。" ]
陈健华(ORCID: 0000-0001-6543-991X),博士,主任医师。
收稿:2023-12-25,
修回:2024-06-10,
纸质出版:2024-07-30
移动端阅览
梁滢昀 综述, 陈健华 审校. 溶瘤病毒联合免疫治疗在恶性肿瘤治疗中的应用进展[J]. 中国癌症杂志, 2024,34(7):686-694.
Yingyun LIANG, Jianhua CHEN. Application progress of oncolytic virus combined with immunotherapy in the treatment of malignant tumors[J]. China Oncology, 2024, 34(7): 686-694.
梁滢昀 综述, 陈健华 审校. 溶瘤病毒联合免疫治疗在恶性肿瘤治疗中的应用进展[J]. 中国癌症杂志, 2024,34(7):686-694. DOI: 10.19401/j.cnki.1007-3639.2024.07.008.
Yingyun LIANG, Jianhua CHEN. Application progress of oncolytic virus combined with immunotherapy in the treatment of malignant tumors[J]. China Oncology, 2024, 34(7): 686-694. DOI: 10.19401/j.cnki.1007-3639.2024.07.008.
溶瘤病毒(oncolytic virus,OV)疗法通过溶瘤病毒在感染的肿瘤细胞内复制、裂解杀死肿瘤细胞,并促进“冷”-“热”肿瘤转换重塑肿瘤免疫微环境,诱导机体免疫系统对肿瘤细胞展开攻击从而达到抗肿瘤治疗的目的。病毒种类、病毒自身特征、宿主免疫力、给药途径及瘤种选择是OV高效发挥抗肿瘤作用的关键。随着基因工程技术的发展,OV可以经过基因编辑改造提高其针对肿瘤细胞的靶向性,增强其复制和裂解细胞的潜能并增强宿主抗肿瘤免疫水平,同时通过联合其他治疗方式可以增强抗肿瘤疗效。肿瘤的异质性是提升肿瘤治疗效果需要突破的瓶颈。鉴于目前临床上单一应用OV疗法的疗效有限,而OV疗法与免疫治疗在抗肿瘤作用机制上存在互补,其联合应用可能为肿瘤治疗提供新的策略。本文从临床获批的OV以及处于研究阶段的天然的或经基因编辑的OV种类、特点及抗肿瘤机制方面展开,同时对处于临床试验阶段的OV治疗进行梳理,总结OV联合治疗策略,尤其是联合以免疫检查点抑制剂(immune checkpoint inhibitor,ICI)和过继细胞疗法(adoptive cell therapy,ACT)为代表的肿瘤免疫治疗进行深入阐述,结合本项目组在OV研究中积累的经验提出OV在抗肿瘤治疗中的思考和展望。
The oncolytic virus (OV) therapy utilizes natural or genetically modified viruses to specifically target and infect tumor cells
leading to the destruction of cancer cells by the replication of the virus itself. This process also alters the immune microenvironment of the tumor transforming “cold” into “hot”
and mobilizes the body's immune system. The effectiveness of oncolytic viruses in anti-tumor therapy depends on factors such as the type of virus
host immunity and route of administration. Immunotherapy aims to activate the immune system and exert anti-tumor effect by relying on autoimmune function. With the development of genetic engineering technology
oncolytic viruses can enhance the anti-tumor effect through gene editing reconstruction
and can be used to treat tumors alone or in combination with other therapies. In view of the limited efficacy of single application of oncolytic virus therapy in clinic
the combination of oncolytic virus therapy and immunotherapy provides a new strategy for tumor treatment. This review started from the types of oncolytic viruses approved in the clinic
characteristics and its anti-tumor mechanisms. At the same time
it combed through the treatment of oncolytic viruses in the clinical trial stage
summarized the combined treatment strategies of oncolytic viruses
especially the combination of tumor immunotherapy represented by immune checkpoint inhibitor (ICI) and adoptive cell therapy (ACT)
and put forward some thoughts and prospects of oncolytic viruses in the anti-tumor treatment in combination with the experience accumulated by the project team in the research of oncolytic viruses.
MA J , RAMACHANDRAN M , JIN C , et al. Characterization of virus-mediated immunogenic cancer cell death and the consequences for oncolytic virus-based immunotherapy of cancer [J ] . Cell Death Dis , 2020 , 11 ( 1 ): 48 . DOI: 10.1038/s41419-020-2236-3 http://doi.org/10.1038/s41419-020-2236-3
FU Q F , CHEN N , GE C L , et al. Prognostic value of tumor-infiltrating lymphocytes in melanoma: a systematic review and meta-analysis [J ] . Oncoimmunology , 2019 , 8 ( 7 ): 1593806 .
HUANG L L , ZHAO H X , SHAN M Y , et al. Oncolytic adenovirus H101 ameliorate the efficacy of anti-PD-1 monotherapy in colorectal cancer [J ] . Cancer Med , 2022 , 11 ( 23 ): 4575 - 4587 .
TODO T , ITO H , INO Y , et al. Intratumoral oncolytic herpes virus G47∆ for residual or recurrent glioblastoma: a phase 2 trial [J ] . Nat Med , 2022 , 28 ( 8 ): 1630 - 1639 . DOI: 10.1038/s41591-022-01897-x http://doi.org/10.1038/s41591-022-01897-x
ANNELS N E , MANSFIELD D , ARIF M , et al. Phase Ⅰ trial of an ICAM-1-targeted immunotherapeutic-coxsackievirus A21 (CVA21) as an oncolytic agent against non muscle-invasive bladder cancer [J ] . Clin Cancer Res , 2019 , 25 ( 19 ): 5818 - 5831 .
BOMMAREDDY P K , SHETTIGAR M , KAUFMAN H L . Integrating oncolytic viruses in combination cancer immunotherapy [J ] . Nat Rev Immunol , 2018 , 18 ( 8 ): 498 - 513 . DOI: 10.1038/s41577-018-0014-6 http://doi.org/10.1038/s41577-018-0014-6
FU X P , ZHANG X L . Potent systemic antitumor activity from an oncolytic herpes simplex virus of syncytial phenotype [J ] . Cancer Res , 2002 , 62 ( 8 ): 2306 - 2312 .
ZHAO J , QIN C , LIU Y Z , et al. Herpes simplex virus and pattern recognition receptors: an arms race [J ] . Front Immunol , 2020 , 11 : 613799 .
GUO Z S , LU B F , GUO Z B , et al. Vaccinia virus-mediated cancer immunotherapy: cancer vaccines and oncolytics [J ] . J Immunother Cancer , 2019 , 7 ( 1 ): 6 . DOI: 10.1186/s40425-018-0495-7 http://doi.org/10.1186/s40425-018-0495-7
TOULMONDE M , COUSIN S , KIND M , et al. Randomized phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced soft-tissue sarcoma [J ] . J Hematol Oncol , 2022 , 15 ( 1 ): 149 .
PORTAL D E , WEISS R E , WOJTOWICZ M , et al. Phase Ⅰ neoadjuvant study of intravesical recombinant fowlpox-GM-CSF (rF-GM-CSF) or fowlpox-TRICOM (rF-TRICOM) in patients with bladder carcinoma [J ] . Cancer Gene Ther , 2020 , 27 ( 6 ): 438 - 447 .
PARK S H , BREITBACH C J , LEE J , et al. Phase 1b trial of biweekly intravenous pexa-vec (JX-594), an oncolytic and immunotherapeutic vaccinia virus in colorectal cancer [J ] . Mol Ther , 2015 , 23 ( 9 ): 1532 - 1540 . DOI: 10.1038/mt.2015.109 http://doi.org/10.1038/mt.2015.109
HEO J , REID T , RUO L , et al. Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer [J ] . Nat Med , 2013 , 19 ( 3 ): 329 - 336 . DOI: 10.1038/nm.3089 http://doi.org/10.1038/nm.3089
PONCE S , CEDRÉS S , RICORDEL C , et al. ONCOS-102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma: a randomized phase 2 study investigating clinical outcomes and the tumor microenvironment [J ] . J Immunother Cancer , 2023 , 11 ( 9 ): e007552 .
ZHU Z , ROBERT MCGRAY A J R , JIANG W J , et al. Improving cancer immunotherapy by rationally combining oncolytic virus with modulators targeting key signaling pathways [J ] . Mol Cancer , 2022 , 21 ( 1 ): 196 . DOI: 10.1186/s12943-022-01664-z http://doi.org/10.1186/s12943-022-01664-z
XIA T L , KONNO H , BARBER G N . Recurrent loss of STING signaling in melanoma correlates with susceptibility to viral oncolysis [J ] . Cancer Res , 2016 , 76 ( 22 ): 6747 - 6759 . DOI: 10.1158/0008-5472.CAN-16-1404 http://doi.org/10.1158/0008-5472.CAN-16-1404
ATASHEVA S , EMERSON C C , YAO J , et al. Systemic cancer therapy with engineered adenovirus that evades innate immunity [J ] . Sci Transl Med , 2020 , 12 ( 571 ): eabc6659 .
MCLAUGHLIN M , PEDERSEN M , ROULSTONE V , et al. The PERK inhibitor GSK2606414 enhances reovirus infection in head and neck squamous cell carcinoma via an ATF4-dependent mechanism [J ] . Mol Ther Oncolytics , 2020 , 16 : 238 - 249 .
DAVOLA M E , MOSSMAN K L . Oncolytic viruses: how “lytic” must they be for therapeutic efficacy? [J ] . Oncoimmunology , 2019 , 8 ( 6 ): e1581528 .
QUAIL D F , JOYCE J A . Microenvironmental regulation of tumor progression and metastasis [J ] . Nat Med , 2013 , 19 ( 11 ): 1423 - 1437 . DOI: 10.1038/nm.3394 http://doi.org/10.1038/nm.3394
ANG L , LI J , DONG H , et al. Chimeric oncolytic adenovirus armed chemokine rantes for treatment of breast cancer [J ] . Bioengineering , 2022 , 9 ( 8 ): 342 .
BRACCI L , SCHIAVONI G , SISTIGU A , et al. Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer [J ] . Cell Death Differ , 2014 , 21 ( 1 ): 15 - 25 . DOI: 10.1038/cdd.2013.67 http://doi.org/10.1038/cdd.2013.67
GUJAR S , POL J G , KIM Y , et al. Antitumor benefits of antiviral immunity: an underappreciated aspect of oncolytic virotherapies [J ] . Trends Immunol , 2018 , 39 ( 3 ): 209 - 221 . DOI: S1471-4906(17)30228-4 http://doi.org/S1471-4906(17)30228-4
LUO Y , LIN C L , ZOU Y D , et al. Tumor-targeting oncolytic virus elicits potent immunotherapeutic vaccine responses to tumor antigens [J ] . Oncoimmunology , 2020 , 9 ( 1 ): 1726168 .
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 .
BELLUCCI R , MARTIN A , BOMMARITO D , et al. Interferon-γ-induced activation of JAK1 and JAK2 suppresses tumor cell susceptibility to NK cells through upregulation of PD-L1 expression [J ] . Oncoimmunology , 2015 , 4 ( 6 ): e1008824 .
DUMMER R , GYORKI D E , HYNGSTROM J , et al. Neoadjuvant talimogene laherparepvec plus surgery versus surgery alone for resectable stage ⅢB-ⅣM1a melanoma: a randomized, open-label, phase 2 trial [J ] . Nat Med , 2021 , 27 ( 10 ): 1789 - 1796 .
CUI C L , WANG X , LIAN B , et al. OrienX010, an oncolytic virus, in patients with unresectable stage ⅢC-Ⅳ melanoma: a phase Ⅰb study [J ] . J Immunother Cancer , 2022 , 10 ( 4 ): e004307 .
MARTINEZ-QUINTANILLA J , SEAH I , CHUA M , et al. Oncolytic viruses: overcoming translational challenges [J ] . J Clin Invest , 2019 , 129 ( 4 ): 1407 - 1418 .
CHEN J H , GAO P , YUAN S J , et al. Oncolytic adenovirus complexes coated with lipids and calcium phosphate for cancer gene therapy [J ] . ACS Nano , 2016 , 10 ( 12 ): 11548 - 11560 . DOI: 10.1021/acsnano.6b06182 http://doi.org/10.1021/acsnano.6b06182
LI Y , LI L J , WANG L J , et al. Selective intra-arterial infusion of rAd-p53 with chemotherapy for advanced oral cancer: a randomized clinical trial [J ] . BMC Med , 2014 , 12 : 16 . DOI: 10.1186/1741-7015-12-16 http://doi.org/10.1186/1741-7015-12-16
ZHANG Y L , QIAN L , CHEN K , et al. Oncolytic adenovirus in treating malignant ascites: a phase Ⅱ trial and longitudinal single-cell study [J ] . Mol Ther , 2024 , 32 ( 6 ): 2000 - 2020 .
DEY M , YU D , KANOJIA D , et al. Intranasal oncolytic virotherapy with CXCR4-enhanced stem cells extends survival in mouse model of glioma [J ] . Stem Cell Reports , 2016 , 7 ( 3 ): 471 - 482 . DOI: S2213-6711(16)30150-3 http://doi.org/S2213-6711(16)30150-3
BELCAID Z , BERREVOETS C , CHOI J , et al. Low-dose oncolytic adenovirus therapy overcomes tumor-induced immune suppression and sensitizes intracranial gliomas to anti-PD-1 therapy [J ] . Neurooncol Adv , 2020 , 2 ( 1 ): vdaa011 .
CHESNEY J A , PUZANOV I , COLLICHIO F A , et al. Talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone for advanced melanoma: 5-year final analysis of a multicenter, randomized, open-label, phase Ⅱ trial [J ] . J Immunother Cancer , 2023 , 11 ( 5 ): e006270 .
BEKAII-SAAB T , KIM R , KIM T W , et al. Third- or later-line therapy for metastatic colorectal cancer: reviewing best practice [J ] . Clin Colorectal Cancer , 2019 , 18 ( 1 ): e117 -e129.
MONGE C , XIE C Q , MYOJIN Y , et al. Phase Ⅰ/Ⅱ study of PexaVec in combination with immune checkpoint inhibition in refractory metastatic colorectal cancer [J ] . J Immunother Cancer , 2023 , 11 ( 2 ): e005640 .
KLEINPETER P , FEND L , THIOUDELLET C , et al. Vectorization in an oncolytic vaccinia virus of an antibody, a Fab and a scFv against programmed cell death-1 (PD-1) allows their intratumoral delivery and an improved tumor-growth inhibition [J ] . Oncoimmunology , 2016 , 5 ( 10 ): e1220467 .
ELLIS G I , SHEPPARD N C , RILEY J L . Genetic engineering of T cells for immunotherapy [J ] . Nat Rev Genet , 2021 , 22 ( 7 ): 427 - 447 . DOI: 10.1038/s41576-021-00329-9 http://doi.org/10.1038/s41576-021-00329-9
CHEN T Y , DING X Q , LIAO Q B , et al. IL-21 arming potentiates the anti-tumor activity of an oncolytic vaccinia virus in monotherapy and combination therapy [J ] . J Immunother Cancer , 2021 , 9 ( 1 ): e001647 .
SANTOS J , HEINIÖ C , QUIXABEIRA D , et al. Systemic delivery of oncolytic adenovirus to tumors using tumor-infiltrating lymphocytes as carriers [J ] . Cells , 2021 , 10 ( 5 ): 978 .
WANG G Q , ZHANG Z L , ZHONG K H , et al. CXCL11-armed oncolytic adenoviruses enhance CAR-T cell therapeutic efficacy and reprogram tumor microenvironment in glioblastoma [J ] . Mol Ther , 2023 , 31 ( 1 ): 134 - 153 .
YE K , LI F , WANG R K , et al. An armed oncolytic virus enhances the efficacy of tumor-infiltrating lymphocyte therapy by converting tumors to artificial antigen-presenting cells in situ [J ] . Mol Ther , 2022 , 30 ( 12 ): 3658 - 3676 . DOI: 10.1016/j.ymthe.2022.06.010 http://doi.org/10.1016/j.ymthe.2022.06.010
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 ): eaaz 1863.
WALSH S R , BASTIN D , CHEN L , et al. Type Ⅰ IFN blockade uncouples immunotherapy-induced antitumor immunity and autoimmune toxicity [J ] . J Clin Invest , 2019 , 129 ( 2 ): 518 - 530 .
ROSEWELL SHAW A , PORTER C E , WATANABE N , et al. Adenovirotherapy delivering cytokine and checkpoint inhibitor augments CAR T cells against metastatic head and neck cancer [J ] . Mol Ther , 2017 , 25 ( 11 ): 2440 - 2451 . DOI: S1525-0016(17)30424-0 http://doi.org/S1525-0016(17)30424-0
ZHENG N B , FANG J , XUE G , et al. Induction of tumor cell autosis by myxoma virus-infected CAR-T and TCR-T cells to overcome primary and acquired resistance [J ] . Cancer Cell , 2022 , 40 ( 9 ): 973 - 985 .e7. DOI: 10.1016/j.ccell.2022.08.001 http://doi.org/10.1016/j.ccell.2022.08.001
PAKOLA S A , PELTOLA K J , CLUBB J H , et al. Safety, efficacy, and biological data of T cell-enabling oncolytic adenovirus TILT-123 in advanced solid cancers from the TUNIMO monotherapy phase Ⅰ trial [J ] . Clin Cancer Res , 2024 . [Epub Ahead of Print ]
0
浏览量
1388
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621