1类新药-重组人nsIL12溶瘤腺病毒注射液

详细说明

　　BioTTT001，是由锤特生物独立开发并准备申报注册的国家I类新药，为一种新型、高效、低毒、靶向性治疗人肿瘤的重组人nsIL12溶瘤腺病毒注射液。该新型病毒载体可作为治疗肿瘤的基因工程药物，同时可诱导机体产生肿瘤治疗性疫苗作用，杀伤远处转移肿瘤细胞和防止肿瘤复发。是目前具有最高效肿瘤杀伤能力和最低毒性的新型肿瘤病毒基因治疗生物制剂。新药临床试验（IND）申请已顺利获得国家药品监督管理局（NMPA）的默示许可。

　　BioTTT001, also knowned as Recombinant Human nsIL12 Oncolytic Adenovirus Injection, is an innovative, high-efficiency, low-toxicity, targeting-therapy drugs of cancer. This innovative oncolytic adenovirus vector was independently developed by Beijing Bio-Targeting Therapeutics Technology Co., Ltd (BioTTT), can inestroy cancers directely and kill distant metastasis, tumor cells and prevent tumor recurrence by induced therapeutic tumor vaccines. We believes BioTTT001 will be a safe, effective therapy to improve the lives of many cancer patients.

　　本产品的适应证为肉眼可见或者显微镜下可见的实体瘤（如头颈部肿瘤、表层肿瘤如黑色素瘤）、转移瘤（腹腔转移瘤）和扩散瘤，通过肿瘤内注射的方式达到治疗肿瘤、预防肿瘤复发和转移的效果。

　　产品简介：

　　产品名：BioTTT001

　　通用名：重组人nsIL12溶瘤腺病毒注射液

　　BioTTT001，是由锤特生物独立开发并拟申报注册的国家I类新药，为一种新型、高效、低毒、靶向性治疗人肿瘤的重组人nsIL12溶瘤腺病毒注射液。该新型病毒载体可作为治疗肿瘤的基因工程药物，同时可诱导机体产生肿瘤治疗性疫苗作用，杀伤远处转移肿瘤细胞和防止肿瘤复发。是目前具有最高效肿瘤杀伤能力和最低毒性的新型肿瘤病毒基因治疗生物制剂。

　　本产品适应证为实体瘤（如头颈部肿瘤、结直肠癌、胰腺癌等）、转移瘤（腹腔转移瘤）和扩散瘤，通过肿瘤内注射、腹腔注射或介入治疗的方式达到治疗肿瘤、预防肿瘤复发和转移的效果。

　　Product Name: BioTTT001

　　Generic Name: Recombinant Human nsIL12 Oncolytic Adenovirus Injection

　　BioTTT001, also knowned as Recombinant Human nsIL12 Oncolytic Adenovirus Injection, is an innovative, high-efficiency, low-toxicity, targeting-therapy drugs of cancer. This innovative oncolytic adenovirus vector was independently developed by Beijing Bio-Targeting Therapeutics Technology Co., Ltd (BioTTT), can inestroy cancers directely and kill distant metastasis, tumor cells and prevent tumor recurrence by induced therapeutic tumor vaccines. We believes BioTTT001 will be a safe, effective therapy to improve the lives of many cancer patients.

　　作用原理：

　　BioTTT001特定靶向带有常见Rb基因和抗凋亡基因异常的人肿瘤细胞，使其能选择性地在肿瘤细胞中复制而不在正常细胞中复制，从而表现出很高的特异性和安全性。

　　BioTTT001通过注射等方法进入体内靶细胞、其周围或者附近后，能够选择性地在肿瘤细胞中复制并溶解肿瘤细胞，释放大量肿瘤相关抗原，与表达的细胞因子人IL-12协同作用，使机体产生高效、特异的抗肿瘤反应，杀伤未被病毒感染的远处肿瘤细胞，包括转移的微小肿瘤细胞灶。在肿瘤细胞中高表达的nsIL12还具有抗肿瘤血管形成等多种作用。

　　BioTTT001 is a type 5 human adenovirus of group C, of which three intrinsic genes E1A-CR2, E1B19K, and E3gp-19K are removed (Therefore named Ad-Triple Deletion, Ad-TD) and the E3B gene that facilitates the expression of viral genes and enhances the persistence of the viruses in vivo is retained. Furthermore, the endogenous promoter of E3gp-19K is retained to drive the expression of the exogenous therapeutic gene—human nsIL12.

　　The vector has a superior anti-tumor efficacy compared to the first generation of onclytic adenovirus. Interleukin 12 (IL12) is well-known as a stimulatory factor for Natural Killer Cell and a maturation factor for Cytotoxic T Lymphocytes, and it is a cytokine heterodimer connected by disulfide bonds, and the two subunits are p35 and p40.

　　The nsIL12 expressed by the BioTTT001 can prevent neovascularization, and more importantly, it can regulate host immunity and produce a synergistic effect with the replicated virus vecter in tumor cells, whereby producing specific anti-tumor immunity in organisms, killing metastatic tumor cells from remote places, and preventing recurrence of tumors.

　　临床前研究：

　　多种人肿瘤细胞系（胰腺癌SUIT2和Capan1、肺癌A549和H1299、食管癌EC9706和ZZB、卵巢癌SKOV3、结直肠癌SW620和HCT116和胃癌AGS）分别感染不同浓度分别感染不同浓度的溶瘤病毒，培养6天检测病毒的杀伤能力，计算EC50值。结果显示，Ad-TD-nsIL-12（BioTTT001）、Ad-TD-IL-12和Ad-TD-LUC对各种人实体瘤细胞系均具有较强的杀伤能力，各病毒组之间无显著性差异。本实验条件下EC50值大多介于0.6 PFU/cell以下，提示BioTTT001体外抗肿瘤能力良好。

　　适 应 证：

　　实体瘤（如头颈部肿瘤、结直肠癌、宫颈癌、表层肿瘤如黑色素瘤、胃癌、胰腺癌等）

　　转移瘤（腹腔转移瘤）、扩散瘤

　　Oncology indications including: locally advanced or metastatic melanoma,  colorectal carcinoma, the head and neck cancer, gastric cancer, pancreatic cancer and metastasis tumor of abdomen. pancreatic cancer.

　　文献资料：

　　1. Tugues S, Burkhard SH, Ohs I, et al. New insights into IL-12-mediated tumor suppression. Cell Death Differ. 2015 Feb;22(2):237-46. (doi: 10.1038/cdd.2014.134)

　　2. Wong HH, Lemoine NR, Wang YH. Oncolytic Viruses for Cancer Therapy: Overcoming the Obstacles. Viruses. 2010 Jan;2(1):78-106. (doi:  10.3390/v2010078)

　　3. Hemminki O, Hemminki A. Chapter 11 - Oncolytic Adenoviruses in the Treatment of Cancer in Humans. Gene Therapy of Cancer (Third Edition), 2014, Pages 153-70. (doi:10.1016/B978-0-12-394295-1.00011-1)

　　4. Wang P, Li X, Wang J, et al. Re-designing Interleukin-12 to enhance its safety andpotential as an anti-tumor immunotherapeutic agent. Nat Commun. 2017 Nov9;8(1):1395. (doi: 10.1038/s41467-017-01385-8)