溶瘤病毒市场及研发格局分析<sup>*</sup>

doi:10.13523/j.cb.2301011

中国生物工程杂志

2023, Vol. 43

Issue (6): 87-101 DOI: 10.13523/j.cb.2301011

行业分析

溶瘤病毒市场及研发格局分析^*

韩佳,范月蕾,毛开云^**(

)

中国科学院上海营养与健康研究所中国科学院上海生命科学信息中心上海 200031

Analysis of Oncolytic Virus Market and R&D Pattern

HAN Jia,FAN Yue-lei,MAO Kai-yun^**(

)

Shanghai Information Center for Life Sciences, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai 200031, China

全文: PDF(974 KB) HTML

摘要：

溶瘤病毒可以感染和破坏癌组织,是一种治疗癌症的新型生物疗法。溶瘤病毒在癌细胞中选择性复制,进而导致癌细胞裂解,释放肿瘤特异性抗原,诱导抗癌免疫反应,充当原位肿瘤疫苗。对病毒进入、复制、诱导和抑制免疫反应机制的深入了解促进了利用病毒治疗人类疾病技术的发展。过去十年溶瘤病毒领域临床试验的进展证实了其对癌症患者的治疗益处,利用溶瘤病毒作为载体治疗特定类型的癌症是肿瘤免疫治疗市场的新增长点。通过全面分析溶瘤病毒免疫治疗市场的细分领域及其市场动态,从关键技术进展、主要企业竞争格局和产品研发进展角度进行分析,并展望溶瘤病毒的发展前景,旨在为相关企业研发方向选择及地区产业决策提供参考。

关键词： 溶瘤病毒; 竞争格局; 研发格局; 市场动态; 肿瘤免疫治疗; 癌症治疗

Abstract:

Oncolytic viruses, capable of infecting and destroying malignant tissues, are becoming new biological therapies for treating cancers. Their ability in selectively replicating inside cancer cells and inducing lysis of certain cancer cells leads to the releasing of tumor-specific antigens for anti-cancer immune responses, acting as in situ cancer vaccines. The insights into the mechanisms of virus replication, entry, induction and inhibition of immune response have promoted the technology development of virus utilization in the treatment of certain human diseases. In the past decade, the progress of clinical trials in the field of oncolytic viruses has confirmed the therapeutic benefits in cancer therpy. Using oncolytic virus as a carrier of foreign genes to treat specific types of cancer is a feasible method, which could become new growth avenue of the cancer immunotherapy market. This article provides a comprehensive and multidimensional analysis of the niche areas and the dynamic changes from several aspects such as the oncolytic virus immunotherapy market, key technology progress, major enterprise competition pattern and product R&D progress, combined with a forecast of the prospects for the development of oncolytic viruses as a cancer therapy, for the purpose of providing reference in research and development direction selection and regional industrial decision-making for related companies.

Key words: Oncolytic virus Competitive pattern R&D pattern Market trends Tumor immnuotherapy Cancer treatment

收稿日期: 2023-01-09 出版日期: 2023-07-04

ZTFLH:

Q819

基金资助: * 上海市2023年度“科技创新行动计划”软科学研究(23692102702);上海市2022年度“科技创新行动计划”软科学研究(22692102900)

通讯作者: **电子信箱:kymao@sinh.ac.cn

	服务
	把本文推荐给朋友
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	韩佳
	范月蕾
	毛开云

引用本文:

韩佳, 范月蕾, 毛开云. 溶瘤病毒市场及研发格局分析^*[J]. 中国生物工程杂志, 2023, 43(6): 87-101.

HAN Jia, FAN Yue-lei, MAO Kai-yun. Analysis of Oncolytic Virus Market and R&D Pattern. China Biotechnology, 2023, 43(6): 87-101.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2301011 或 https://manu60.magtech.com.cn/biotech/CN/Y2023/V43/I6/87

表1 溶瘤病毒产品的主要类型

图1 溶瘤病毒药物的适应证

表2 中国溶瘤病毒药物行业发展的相关利好政策

图2 溶瘤病毒临床试验不同区域占比

图3 溶瘤病毒临床试验进行数量的主要国家年度比较

表3 溶瘤病毒行业国内外代表性企业

病毒种类	产品名称	制药公司	给药途径	临床阶段	临床研究适应症
腺病毒	Onyx-015	Onyx 制药	瘤内	Ⅱ	头颈癌、胰腺癌、卵巢癌、结直肠癌、肝癌等
腺病毒	DNX-2401	DNAtrix公司	瘤内	Ⅱ	卵巢癌
腺病毒	Colo-Ad1	PsiOxus 制药	瘤内	Ⅱ	非小细胞肺癌、肾癌、膀胱癌、卵巢癌等
腺病毒	ProstAtak	Adventagene公司	瘤内	Ⅲ	胰腺癌、肺癌、乳腺癌、前列腺癌等
腺病毒	Oncos-102	Oncos Therapeutics	瘤内	Ⅱ	卵巢瘤、直肠癌等
腺病毒	CG0070	Cold Genesys公司	瘤内	Ⅲ	膀胱癌
腺病毒	OBP-301	Oncolys 生物制药	瘤内	Ⅱ	食管癌、胃癌、肝癌、黑色素瘤
痘病毒	Pexa-vec	Jennerex生物治疗	瘤内静脉	Ⅲ	黑色素瘤、肝癌、乳腺癌、结直肠癌
痘病毒	GL-ONC1	Gnenelux	瘤内静脉腹腔注射	Ⅱ	肺癌、头颈癌、间皮瘤
疱疹病毒	G207	Treovir 公司	瘤内	Ⅱ	神经母细胞瘤
疱疹病毒	HF10	TaKaRa 公司	瘤内	Ⅱ	乳腺癌、黑色素瘤、胰腺癌
疱疹病毒	SEPREHVIR	Sorrento 制药	瘤内	Ⅱ	肝癌、间皮瘤、神经母细胞瘤、胶质母细胞瘤
疱疹病毒	OrienX010	北京奥源和力	瘤内	Ⅱ	神经母细胞瘤
疱疹病毒	RP1	Replimune公司	瘤内	Ⅱ	软组织肉瘤、黑色素瘤、皮肤癌、非小细胞肺癌
疱疹病毒	DS-1647	第一三共株式会社	瘤内	Ⅱ	胶质母细胞瘤、前列腺癌、神经母细胞瘤、间皮瘤
疱疹病毒	OH2	武汉滨会	瘤内	Ⅱ	结直肠癌、膀胱癌
疱疹病毒	T-Vec	安进公司	瘤内	Ⅲ	黑色素瘤、乳腺癌、头颈鳞癌、肝癌、肉瘤、淋巴瘤、皮肤癌
疱疹病毒	MVR-T3011	深圳亦诺微	瘤内静脉	Ⅱ	肺癌、肝癌、结直肠癌、子宫内膜癌
呼肠孤病毒	Reolysin	Oncolytics公司	瘤内静脉腹腔注射	Ⅲ	胶质瘤、肉瘤、结直肠癌、非小细胞肺癌、卵巢癌
柯萨奇病毒	Cavatak	Viralytics公司	瘤内腹腔	Ⅱ	黑色素瘤、胰腺癌、头颈癌、乳腺癌、前列腺癌等
麻疹病毒	MV-NIS	Vyriad公司	瘤内膀胱内	Ⅱ	输卵管癌、肉瘤、腹膜癌、子宫内膜样腺癌、卵巢癌

表4 Ⅱ期和Ⅲ期临床试验阶段的部分溶瘤病毒产品

[1]	Kelly E, Russell S J. History of oncolytic viruses: genesis to genetic engineering. Molecular Therapy, 2007, 15(4): 651-659. doi: 10.1038/sj.mt.6300108 pmid: 17299401
[2]	Vellinga J, Van der Heijdt S, Hoeben R C. The adenovirus capsid: major progress in minor proteins. Journal of General Virology, 2005, 86(6): 1581-1588. doi: 10.1099/vir.0.80877-0
[3]	Arnberg N. Adenovirus receptors: implications for targeting of viral vectors. Trends in Pharmacological Sciences, 2012, 33(8): 442-448. doi: 10.1016/j.tips.2012.04.005 pmid: 22621975
[4]	Dai M H, Zamarin D, Gao S P, et al. Synergistic action of oncolytic Herpes simplex virus and radiotherapy in pancreatic cancer cell lines. The British Journal of Surgery, 2010, 97(9): 1385-1394. doi: 10.1002/bjs.7124
[5]	De Clercq E. Antiviral drugs in current clinical use. Journal of Clinical Virology, 2004, 30(2): 115-133. doi: 10.1016/j.jcv.2004.02.009 pmid: 15125867
[6]	Diefenbach R, Sokolowski N, Rizos H. Oncolytic virotherapy using Herpes simplex virus: how far have we come? Oncolytic Virotherapy, 2015, 4: 207-219. doi: 10.2147/OV.S66086 pmid: 27512683
[7]	Chhikara B S, Parang K. Global cancer statistics 2022: the trends projection analysis. Chemical Biology Letters, 2023, 10(1): 451-451.
[8]	Nabors L B, Portnow J, Ammirati M, et al. Central nervous system cancers, version 1.2015. Journal of the National Comprehensive Cancer Network, 2015, 13(10): 1191-1202. doi: 10.6004/jnccn.2015.0148 pmid: 26483059
[9]	Corrado G, Salutari V, Palluzzi E, et al. Optimizing treatment in recurrent epithelial ovarian cancer. Expert Review of Anticancer Therapy, 2017, 17(12): 1147-1158. doi: 10.1080/14737140.2017.1398088 pmid: 29086618
[10]	Casali P G. Adjuvant chemotherapy for soft tissue sarcoma. American Society of Clinical Oncology Educational Book, 2015(35): e629-e633.
[11]	Flaig T W, Spiess P E, Agarwal N, et al., Bladder cancer, version 3.2020, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw, 2020, 18(3): 329-354. doi: 10.6004/jnccn.2020.0011
[12]	Feola S, Russo S, Ylösmäki E, et al. Oncolytic ImmunoViroTherapy: a long history of crosstalk between viruses and immune system for cancer treatment. Pharmacology & Therapeutics, 2022, 236: 108103.
[13]	Puzanov I, Milhem M, Minor D, et al. Talimogene laherparepvec in combination with ipilimumab in previously untreated, unresectable stage IIIB-IV melanoma. J Clin Oncol, 2016, 34(22): 2619-2626. doi: 10.1200/JCO.2016.67.1529 pmid: 27298410
[14]	Chesney Jason A, Antoni R, Long Georgina V, et al. Randomized, double-blind, placebo-controlled, global phase III trial of talimogene laherparepvec combined with pembrolizumab for advanced melanoma. Journal of Clinical Oncology, 2023, 41(3): 528-540.
[15]	Gujar S, Bell J, Diallo J S. SnapShot: cancer immunotherapy with oncolytic viruses. Cell, 2019, 176(5): 1240-1240.e1. doi: S0092-8674(19)30114-X pmid: 30794777
[16]	Twumasi-Boateng K, Pettigrew J L, Eunice Kwok Y Y, et al. Oncolytic viruses as engineering platforms for combination immunotherapy. Nature Reviews Cancer, 2018, 18(7): 419-432. doi: 10.1038/s41568-018-0009-4 pmid: 29695749
[17]	Wan P K T, Ryan A J, Seymour L W. Beyond cancer cells: targeting the tumor microenvironment with gene therapy and armed oncolytic virus. Molecular Therapy, 2021, 29(5): 1668-1682. doi: 10.1016/j.ymthe.2021.04.015
[18]	Pol J G, Workenhe S T, Konda P, et al. Cytokines in oncolytic virotherapy. Cytokine & Growth Factor Reviews, 2020, 56: 4-27.
[19]	Jiang H, Shin D, Nguyen T T, et al. Localized treatment with oncolytic adenovirus delta-24-RGDOX induces systemic immunity against disseminated subcutaneous and intracranial melanomas. Clinical Cancer Research, 2019, 25: 6801-6814. doi: 10.1158/1078-0432.CCR-19-0405 pmid: 31455679
[20]	Passaro C, Alayo Q, De Laura I, et al., Arming an oncolytic Herpes simplex virus type 1 with a single-chain fragment variable antibody against PD-1 for experimental glioblastoma therapy. Clin Cancer Res, 2019, 25(1): 290-299. doi: 10.1158/1078-0432.CCR-18-2311
[21]	Su Y H, Su C Q, Qin L X. Current landscape and perspective of oncolytic viruses and their combination therapies. Translational Oncology, 2022, 25: 101530. doi: 10.1016/j.tranon.2022.101530
[22]	Maroun J, Muñoz-Alía M, Ammayappan A, et al. Designing and building oncolytic viruses. Future Virology, 2017, 12(4): 193-213. doi: 10.2217/fvl-2016-0129 pmid: 29387140
[23]	Liu B L, Robinson M, Han Z Q, et al. ICP34.5 deleted Herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties. Gene Therapy, 2003, 10(4): 292-303. doi: 10.1038/sj.gt.3301885 pmid: 12595888
[24]	Andtbacka R H, Kaufman H L, Collichio F, et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol, 2015, 33(25): 2780-2788. doi: 10.1200/JCO.2014.58.3377 pmid: 26014293
[25]	Liang M. Oncorine, the world first oncolytic virus medicine and its update in China. Current Cancer Drug Targets, 2018, 18(2): 171-176. doi: 10.2174/1568009618666171129221503
[26]	Chan W M, McFadden G. Oncolytic poxviruses. Annual Review of Virology, 2014, 1: 191-214. doi: 10.1146/virology.2014.1.issue-1
[27]	Zhang Q, Zhang J W, Tian Y F, et al. Efficacy of a novel double-controlled oncolytic adenovirus driven by the Ki 67 core promoter and armed with IL-15 against glioblastoma cells. Cell Biosci, 2020, 10: 124. doi: 10.1186/s13578-020-00485-1 pmid: 33133514
[28]	Huang H Y, Liu Y Q, Liao W X, et al. Oncolytic adenovirus programmed by synthetic gene circuit for cancer immunotherapy. Nature Communications, 2019, 10(1): 1-15. doi: 10.1038/s41467-018-07882-8
[29]	Raimondi G, Gea-Sorlí S, Otero-Mateo M, et al. Inhibition of miR-222 by oncolytic adenovirus-encoded miRNA sponges promotes viral oncolysis and elicits antitumor effects in pancreatic cancer models. Cancers, 2021, 13(13): 3233. doi: 10.3390/cancers13133233
[30]	Froechlich G, Caiazza C, Gentile C, et al. Integrity of the antiviral STING-mediated DNA sensing in tumor cells is required to sustain the immunotherapeutic efficacy of Herpes simplex oncolytic virus. Cancers, 2020, 12(11): 3407. doi: 10.3390/cancers12113407
[31]	Eriksson E, Milenova I, Wenthe J, et al. Shaping the tumor stroma and sparking immune activation by CD40 and 4-1BB signaling induced by an armed oncolytic virus. Clin Cancer Res, 2017. 23(19): 5846-5857. doi: 10.1158/1078-0432.CCR-17-0285 pmid: 28536305
[32]	Andarini S, Kikuchi T, Nukiwa M, et al. Adenovirus vector-mediated in vivo Gene transfer of OX40 ligand to tumor cells enhances antitumor immunity of tumor-bearing hosts. Cancer Research, 2004, 64(9): 3281-3287. doi: 10.1158/0008-5472.can-03-3911 pmid: 15126371
[33]	Autio K, Knuuttila A, Kipar A, et al. Safety and biodistribution of a double-deleted oncolytic vaccinia virus encoding CD 40 ligand in laboratory Beagles. Molecular Therapy - Oncolytics, 2014, 1: 14002. doi: 10.1038/mto.2014.2
[34]	Kaufman H L. Targeting the local tumor microenvironment with vaccinia virus expressing B7.1 for the treatment of melanoma. Journal of Clinical Investigation, 2005, 115(7): 1903-1912. doi: 10.1172/JCI24624 pmid: 15937544
[35]	Wenthe J, Naseri S, Hellström A C, et al. Immunostimulatory oncolytic virotherapy for multiple myeloma targeting 4-1BB and/or CD40. Cancer Gene Therapy, 2020, 27(12): 948-959. doi: 10.1038/s41417-020-0176-9
[36]	Wenthe J, Naseri S, Labani-Motlagh A, et al. Boosting CAR T-cell responses in lymphoma by simultaneous targeting of CD40/4-1BB using oncolytic viral gene therapy. Cancer Immunology, Immunotherapy, 2021, 70(10): 2851-2865. doi: 10.1007/s00262-021-02895-7
[37]	Ylösmäki E, Ylösmäki L, Fusciello M, et al. Characterization of a novel OX40 ligand and CD40 ligand-expressing oncolytic adenovirus used in the PeptiCRAd cancer vaccine platform. Molecular Therapy - Oncolytics, 2021, 20: 459-469. doi: 10.1016/j.omto.2021.02.006
[38]	Rosen L S, Camidge D R, Khalil D, et al. FORTITUDE: results of a phase 1a study of the novel transgene-armed and tumor-selective vector NG-350A with and without pembrolizumab (pembro). Journal of Clinical Oncology, 2022, 40(16_suppl): 2559. doi: 10.1200/JCO.2022.40.16_suppl.2559
[39]	Jiang H, Rivera-Molina Y, Gomez-Manzano C, et al. Oncolytic adenovirus and tumor-targeting immune modulatory therapy improve autologous cancer vaccination. Cancer Research, 2017, 77(14): 3894-3907. doi: 10.1158/0008-5472.CAN-17-0468 pmid: 28566332
[40]	Chaurasiya S, Fong Y, Warner S G. Optimizing oncolytic viral design to enhance antitumor efficacy: progress and challenges. Cancers, 2020, 12(6): 1699. doi: 10.3390/cancers12061699
[41]	Vilgelm A E, Richmond A. Chemokines modulate immune surveillance in tumorigenesis, metastasis, and response to immunotherapy. Frontiers in Immunology, 2019, 10: 333. doi: 10.3389/fimmu.2019.00333 pmid: 30873179
[42]	Mgrditchian T, Arakelian T, Paggetti J, et al. Targeting autophagy inhibits melanoma growth by enhancing NK cells infiltration in a CCL5-dependent manner. Proceedings of the National Academy of Sciences of the United States of America, 2017, 114(44): e9271-e9279.
[43]	Li J, O’Malley M, Urban J, et al. Chemokine expression from oncolytic vaccinia virus enhances vaccine therapies of cancer. Molecular Therapy, 2011, 19(4): 650-657. doi: 10.1038/mt.2010.312 pmid: 21266959
[44]	Li F, Sheng Y Q, Hou W, et al. CCL5-armed oncolytic virus augments CCR5-engineered NK cell infiltration and antitumor efficiency. 2020, 8(1) :e000131.
[45]	Tian Y M, Xie D Y, Yang L. Engineering strategies to enhance oncolytic viruses in cancer immunotherapy. Signal Transduction and Targeted Therapy, 2022, 7: 117. doi: 10.1038/s41392-022-00951-x pmid: 35387984
[46]	Qiu Y, Su M X, Liu L Y, et al. Clinical application of cytokines in cancer immunotherapy. Drug Design, Development and Therapy, 2021, 15: 2269-2287. doi: 10.2147/DDDT.S308578 pmid: 34079226
[47]	Shiomi A, Usui T. Pivotal roles of GM-CSF in autoimmunity and inflammation. Mediators of Inflammation, 2015, 2015: 1-13.
[48]	Pol J, Kroemer G, Galluzzi L. First oncolytic virus approved for melanoma immunotherapy. OncoImmunology, 2016, 5(1): e1115641. doi: 10.1080/2162402X.2015.1115641
[49]	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. Annals of Surgical Oncology, 2010, 17(3): 718-730. doi: 10.1245/s10434-009-0809-6 pmid: 19915919
[50]	Kim K J, Moon D, Kong S J, et al., Antitumor effects of IL-12 and GM-CSF co-expressed in an engineered oncolytic HSV-1. Gene Ther, 2021, 28(3-4): 186-198. doi: 10.1038/s41434-020-00205-x
[51]	Lee J H, Roh M S, Lee Y K, et al. Oncolytic and immunostimulatory efficacy of a targeted oncolytic poxvirus expressing human GM-CSF following intravenous administration in a rabbit tumor model. Cancer Gene Therapy, 2010, 17(2): 73-79. doi: 10.1038/cgt.2009.50 pmid: 19629143
[52]	Lemay C G, Rintoul J L, Kus A, et al. Harnessing oncolytic virus-mediated antitumor immunity in an infected cell vaccine. Molecular Therapy, 2012, 20(9): 1791-1799. doi: 10.1038/mt.2012.128 pmid: 22760544
[53]	Robinson M, Li B, Ge Y, et al. Novel immunocompetent murine tumor model for evaluation of conditionally replication-competent (oncolytic) murine adenoviral vectors. Journal of Virology, 2009, 83(8): 3450-3462. doi: 10.1128/JVI.02561-08 pmid: 19193803
[54]	Kemp V, van den Wollenberg D J M, Camps M G M, et al. Arming oncolytic reovirus with GM-CSF gene to enhance immunity. Cancer Gene Therapy, 2019, 26(9): 268-281. doi: 10.1038/s41417-018-0063-9
[55]	Konrad M W, Hemstreet G, Hersh E M, et al. Pharmacokinetics of recombinant interleukin 2 in humans. Cancer Research, 1990, 50(7): 2009-2017. pmid: 2317789
[56]	Liu Z Q, Ge Y, Wang H Y, et al. Modifying the cancer-immune set point using vaccinia virus expressing re-designed interleukin-2. Nature Communications, 2018, 9(1): 1-9. doi: 10.1038/s41467-017-02088-w
[57]	Koeller J M. Biologic response modifiers: the interferon Alfa experience. American Journal of Hospital Pharmacy, 1989, 46(11_Suppl): S11-S15.
[58]	Bourgeois-Daigneault M C, Roy D G, Falls T, et al. Oncolytic vesicular stomatitis virus expressing interferon-σ has enhanced therapeutic activity. Molecular Therapy - Oncolytics, 2016, 3: 16001. doi: 10.1038/mto.2016.1
[59]	Su C Q, Peng L H, Sham J, et al. Immune gene-viral therapy with triplex efficacy mediated by oncolytic adenovirus carrying an interferon-γ gene yields efficient antitumor activity in immunodeficient and immunocompetent mice. Molecular Therapy, 2006, 13(5): 918-927. doi: 10.1016/j.ymthe.2005.12.011
[60]	Daud A I, Wolchok J D, Robert C, et al. Programmed death-ligand 1 expression and response to the anti-programmed death 1 antibody pembrolizumab in melanoma. J Clin Oncol, 2016, 34(34): 4102-4109. pmid: 27863197
[61]	Kelly K R, Espitia C M, Zhao W, et al. Oncolytic reovirus sensitizes multiple myeloma cells to anti-PD-L1 therapy. Leukemia, 2018, 32(1): 230-233. doi: 10.1038/leu.2017.272 pmid: 28832023
[62]	Chesney J, Puzanov I, Collichio F, et al. Randomized, open-label phase II study evaluating the efficacy and safety of talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone in patients with advanced, unresectable melanoma. J Clin Oncol, 2018. 36(17): 1658-1667. doi: 10.1200/JCO.2017.73.7379 pmid: 28981385
[63]	Moon E K, Wang L C S, Bekdache K, et al. Intra-tumoral delivery of CXCL 11 via a vaccinia virus, but not by modified T cells, enhances the efficacy of adoptive T cell therapy and vaccines. OncoImmunology, 2018, 7(3): e1395997. doi: 10.1080/2162402X.2017.1395997
[64]	Nishio N, Dotti G. Oncolytic virus expressing RANTES and IL-15 enhances function of CAR-modified T cells in solid tumors. OncoImmunology, 2015, 4(2): e988098. doi: 10.4161/21505594.2014.988098
[65]	Soliman H, Hogue D, Han H, et al. A phase I trial of talimogene laherparepvec in combination with neoadjuvant chemotherapy for the treatment of nonmetastatic triple-negative breast cancer. Clin Cancer Res, 2021, 27(4): 1012-1018. doi: 10.1158/1078-0432.CCR-20-3105 pmid: 33219014

[1]	韩佳, 张博文, 毛开云. 新型药物递送系统研发格局分析^*[J]. 中国生物工程杂志, 2023, 43(2/3): 1-14.
[2]	张慧,陈华宁,库德莱迪·库尔班,王松娜,刘嘉扬,赵缜,叶丽. Wnt/β-catenin信号通路与癌症发生发展及其免疫治疗^*[J]. 中国生物工程杂志, 2022, 42(1/2): 104-111.
[3]	毛开云,李荣,李丹丹,赵若春,范月蕾,江洪波. 全球双特异性抗体药物研发格局分析^*[J]. 中国生物工程杂志, 2021, 41(11): 110-118.
[4]	张保惠,熊华龙,张天英,袁权. 基于水疱性口炎病毒(VSV)的溶瘤病毒研究进展 ^*[J]. 中国生物工程杂志, 2020, 40(6): 53-62.
[5]	吕海银,王腾飞,裴仁军. 基于核酸适配体的肿瘤免疫治疗进展 ^*[J]. 中国生物工程杂志, 2019, 39(6): 55-61.
[6]	曲殿波, 刘传暄, 马清钧. 肿瘤免疫治疗的一种新技术——肽脉冲[J]. 中国生物工程杂志, 1998, 18(4): 58-63.

Viewed

Full text

Abstract

Cited

Shared

Discussed