更新于：2024-04-01

HPV E7

人乳头瘤病毒E7蛋白

更新于：2024-04-01

基本信息

别名

乳头状瘤病毒属E7蛋白质、E7、Protein E7

简介

Plays a role in viral genome replication by driving entry of quiescent cells into the cell cycle. Stimulation of progression from G1 to S phase allows the virus to efficiently use the cellular DNA replicating machinery to achieve viral genome replication. E7 protein has both transforming and trans-activating activities. Induces the disassembly of the E2F1 transcription factor from RB1, with subsequent transcriptional activation of E2F1-regulated S-phase genes. Interferes with host histone deacetylation mediated by HDAC1 and HDAC2, leading to transcription activation. Also plays a role in the inhibition of both antiviral and antiproliferative functions of host interferon alpha. Interaction with host TMEM173/STING impairs the ability of TMEM173/STING to sense cytosolic DNA and promote the production of type I interferon (IFN-alpha and IFN-beta).

关联

项与 HPV E7 相关的药物

INO-3107

靶点-

作用机制

E7抑制剂 [+1]

在研机构

Inovio Pharmaceuticals, Inc.

原研机构

University of Pennsylvania

在研适应症

复发性呼吸道乳头状瘤病

非在研适应症

套细胞淋巴瘤

最高研发阶段申请上市

首次获批国家/地区-

首次获批日期1800-01-20

Bizalimogene ralaplasmid(University of Pennsylvania)

靶点

E6 x HPV E7

作用机制

E6抑制剂 [+1]

在研机构

Inovio Pharmaceuticals, Inc. [+1]

原研机构

University of Pennsylvania

在研适应症

鳞状上皮内病变 [+1]

非在研适应症

肛门肿瘤 [+4]

最高研发阶段临床3期

首次获批国家/地区-

首次获批日期1800-01-20

HPV 16 E7/HSP70 fused DNA vaccine(The Johns Hopkins University)

靶点

HPV E7 x HSPA1A

作用机制

E7调节剂 [+1]

在研机构

The Johns Hopkins University

原研机构

The Johns Hopkins University

在研适应症

卵巢癌 [+2]

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

项与 HPV E7 相关的临床试验

NCT06223568 / Not yet recruiting临床2期IIT

Phase II Trial of Neoadjuvant Chemotherapy (NAC) Alone or in Combination With Immunotherapy Vaccine PRGN-2009 in Subjects With Newly Diagnosed HPV-Associated Oropharyngeal (Head and Neck) Cancer

Background:
Throat cancer is a common tumor that can occur in people infected with the human papilloma virus (HPV). Most people with this cancer survive more than 5 years with standard chemotherapy drugs plus radiation. But radiation can cause serious adverse effects. Researchers believe that adding a vaccine (PRGN-2009) to this drug therapy may improve survival without the need for radiation.
Objective:
To test a study vaccine combined with standard chemotherapy in patients with HPV-associated throat cancers.
Eligibility:
People aged 18 years and older with newly diagnosed throat cancer associated with HPV.
Design:
Participants will be screened. They will have a physical exam and blood tests. They will have imaging scans and tests of their heart function and hearing. They will provide a sample of tissue from their tumor. A recent sample may be used; if none is available, a new sample will be taken.
All participants will get two common drugs for treating cancer. These drugs are given through a tube attached to a needle inserted into a vein in the arm. Participants will receive these drugs on the first day of three 3-week cycles.
Half of the participants will also get the vaccine. PRGN-2009 is injected under the skin in the arm. They will get these shots 4 times: 7 days before the start of the first cycle and on the 11th day of each cycle.
Participants will have standard surgery to remove their tumors 3 to 6 weeks after completing the study treatment. They will have follow-up visits 3, 6, 12, and 24 months after their surgery.

开始日期2024-04-03

申办/合作机构

National Cancer Institute

NCT06157151 / Recruiting临床2期

A Randomized, Open-label, Two-arm, Phase 2 Study to Evaluate Efficacy and Safety of PRGN-2009 in Combination With Pembrolizumab Versus Pembrolizumab in Patients With Recurrent or Metastatic Cervical Cancer.

This randomized trial will evaluate the efficacy and safety of PRGN-2009 in combination with pembrolizumab compared to pembrolizumab alone in patients with pembrolizumab-resistant recurrent or metastatic cervical cancer.

开始日期2024-02-20

申办/合作机构

Precigen, Inc.

[+1]

NCT05996523 / Recruiting临床2期IIT

Phase II Trial of Immunotherapeutic HPV Vaccine PRGN-2009 With Pembrolizumab Before Standard Treatment in Subjects With Newly Diagnosed HPV-Associated Oropharyngeal Cancer

Background:
Cancers in and around the mouth associated with human papilloma virus (HPV) are common. Two treatments (the drug pembrolizumab and the HPV vaccine PRGN-2009) have been shown to work well when used individually against these cancers. Researchers want to find out if they might work better when used together.
Objective:
To test pembrolizumab combined with PRGN-2009 in people with HPV-positive cancers in and around the mouth.
Eligibility:
Adults aged 18 and older newly diagnosed with HPV-positive cancers in and around the mouth.
Design:
Participants will be screened. They will have a physical exam with blood tests. They will have imaging scans. They may need to have a biopsy: A sample of tissue will be taken from the tumor.
PRGN-2009 is given as an injection under the skin. Pembrolizumab is given through a tube attached to a needle inserted into a vein in the arm.
Participants will have at least 3 clinic visits: At the first, they will receive both the drug and the vaccine; 15 days later, they will receive a second shot of the vaccine. At the third visit, about 1 week after the second, they will have follow-up tests.
During these visits, participants will give samples of blood, urine, and saliva. Imaging scans and biopsies will be repeated. They will have tests of their heart function.
Participants may opt to return for another follow-up visit about 1 month after their second dose of the vaccine.
Participants will have follow-up contacts by phone 3 and 6 months after starting the study. The calls will continue once a year for 5 years.

开始日期2023-11-07

申办/合作机构

National Cancer Institute

100 项与 HPV E7 相关的临床结果

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100 项与 HPV E7 相关的转化医学

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0 项与 HPV E7 相关的专利（医药）

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6,114

项与 HPV E7 相关的文献（医药）

2024-12-01·Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology

Human papillomavirus type 16 E7 promotes cell viability and migration in cervical cancer by regulating the miR-23a/HOXC8 axis.

Article

作者: Yahang Chen ; Lei Sun ; Lin Li

BACKGROUND:

Human papillomavirus (HPV) is a risk factor for the occurrence of cervical cancer (CC). Here, we aimed to explore the role of HPV16 in CC and identify the underlying mechanism.

METHODS:

The expression of miR-23a, HPV16 E6/E7 and homeobox C8 (HOXC8) was measured by quantitative real-time PCR or western blot. Cell viability and migration were evaluated using cell counting kit-8, Transwell and wound healing assays. The targeting relationship between miR-23a and HOXC8 was revealed by dual-luciferase reporter assay.

RESULTS:

miR-23a was downregulated in HPV16-positive (HPV16+) CC tissues and HPV16+ and HPV18+ cells. Additionally, E6/E7 expression was increased in CC cells. Then, we found that E7, rather than E6, positively regulated miR-23a expression. miR-23a suppressed cell viability and migration, whereas E7 overexpression abrogated this suppression. miR-23a targeted HOXC8, which reversed miR-23a-mediated cell viability and migration.

CONCLUSIONS:

HPV16 E7-mediated miR-23a suppressed CC cell viability and migration by targeting HOXC8, suggesting a novel mechanism of HPV-induced CC.

2024-02-19·Diagnostics (Basel, Switzerland)

Enhancing Cervical Cancer Screening: Review of p16/Ki-67 Dual Staining as a Promising Triage Strategy.

Review

作者: Yung-Taek Ouh ; Ho Yeon Kim ; Kyong Wook Yi ; Nak-Woo Lee ; Hai-Joong Kim ; Kyung-Jin Min

Cervical cancer, primarily caused by high-risk human papillomavirus (HR-HPV) types 16 and 18, is a major global health concern. Persistent HR-HPV infection can progress from reversible precancerous lesions to invasive cervical cancer, which is driven by the oncogenic activity of human papillomavirus (HPV) genes, particularly E6 and E7. Traditional screening methods, including cytology and HPV testing, have limited sensitivity and specificity. This review explores the application of p16/Ki-67 dual-staining cytology for cervical cancer screening. This advanced immunocytochemical method allows for simultaneously detecting p16 and Ki-67 proteins within cervical epithelial cells, offering a more specific approach for triaging HPV-positive women. Dual staining and traditional methods are compared, demonstrating their high sensitivity and negative predictive value but low specificity. The increased sensitivity of dual staining results in higher detection rates of CIN2+ lesions, which is crucial for preventing cervical cancer progression. However, its low specificity may lead to increased false-positive results and unnecessary biopsies. The implications of integrating dual staining into contemporary screening strategies, particularly considering the evolving landscape of HPV vaccination and changes in HPV genotype prevalence, are also discussed. New guidelines and further research are necessary to elucidate the long-term effects of integrating dual staining into screening protocols.

2024-02-16·Cancer immunology research

Tsyn-seq: a T cell synapse-based antigen identification platform.

Article

作者: Yimei Jin ; Takahiko Miyama ; Alexandria Brown ; Tomo Hayase ; Xingzhi Song ; Anand K Singh ; Licai Huang ; Ivonne I Flores ; Lauren K McDaniel ; Israel Glover ; Taylor M Halsey ; Rishika Prasad ; Valerie Chapa ; Saira Ahmed ; Jianhua Zhang ; Kunal Rai ; Christine B Peterson ; Gregory Lizee ; Jennifer Karmouch ; Eiko Hayase ; Jeffrey J Molldrem ; Chia-Chi Chang ; Wen-Bin Tsai ; Robert R Jenq

Tools for genome-wide rapid identification of peptide-major histocompatibility complex targets of T-cell receptors (TCRs) are not yet universally available. We present a new antigen screening method, the T-synapse (Tsyn) reporter system, which includes antigen-presenting cells (APCs) with a Fas-inducible NF-κB reporter and T cells with a nuclear factor of activated T cells (NFAT) reporter. To functionally screen for target antigens from a cDNA library, productively interacting T cell-APC aggregates were detected by dual reporter activity and enriched by flow sorting followed by antigen identification quantified by deep sequencing (Tsyn-seq). When applied to a previously characterized TCR specific for the E7 antigen derived from human papillomavirus type 16 (HPV16), Tsyn-seq successfully enriched the correct cognate antigen from a cDNA library derived from an HPV16-positive cervical cancer cell line. Tsyn-seq provides a method for rapidly identifying antigens recognized by TCRs of interest from a tumor cDNA library.

项与 HPV E7 相关的新闻（医药）

2024-03-26

·生物谷

Mol Cancer: CCL11可能是一种有效的抗癌T细胞增强剂

本研究中，研究者系统地评估了趋化因子融合的hpv16e6 /E7抗原在体内改善核苷酸疫苗诱导的细胞和体液免疫反应。由mRNA或DNA抗原前体组成的核苷酸疫苗被宿主细胞吸收，其核苷酸序列在细胞内被翻译成抗原。然后，这些抗原可以被细胞质中的蛋白酶体降解，生成MHC-I分子的表位肽，并激活细胞毒性反应。细胞外分泌的抗原被抗原呈递细胞(APCs)吞噬，同时触发T辅助细胞或体液免疫。核苷酸疫苗的特性赋予它们不仅在预防方面而且在治疗方面治疗癌症等疾病的能力。个体化RNA突变体疫苗成功地免疫了黑色素瘤患者，产生了良好的t细胞应答，延长了无进展生存期。核酸疫苗的免疫原性是成功的关键。因此，进一步的改进是非常可取的。图片来源：https://doi.org/10.1186/s12943-024-01958-4 近日，来自中国医学科学院药物生物技术研究所的研究者们在Mol Cancer杂志上发表了题为“Genetic fusion of CCL11 to antigens enhances antigenicity in nucleic acid vaccines and eradicates tumor mass through optimizing T-cell response”的文章，该研究表明CCL11可能是一种有效的抗癌T细胞增强剂。核酸疫苗在治疗癌症方面显示出良好的效力和功效，具有强大和特异性的T细胞反应。改善递送抗原的免疫原性有助于延长治疗疗效并降低剂量依赖性毒性。在这里，研究者系统地评估了趋化因子融合的hpv16e6 /E7抗原在体内改善核苷酸疫苗诱导的细胞和体液免疫反应。研究发现，与不同趋化因子的融合改变了针对抗原的免疫反应的性质。虽然许多趋化因子能够单独或同时放大特定的CD8 + T细胞或体液反应，CCL11被认为是改善免疫原性、促进特异性CD8 + T细胞干细胞性和产生肿瘤排斥反应的最有效的趋化因子。将CCL11与E6/E7抗原融合作为治疗性DNA疫苗显著提高了治疗效果，并在92%的携带肿瘤的小鼠中根除了已建立的大肿瘤(n = 25)。与CCL11融合的抗原扩大了特异性T细胞的TCR多样性，诱导活化的特异性T细胞、中性粒细胞、巨噬细胞和树突状细胞(dc)向肿瘤浸润，形成对肿瘤致命的综合免疫微环境。DNA疫苗联合抗CTLA4治疗进一步增强了治疗效果。此外，CCL11还可用于mRNA疫苗设计。不同的趋化因子可以形成抗原诱导的免疫类型图片来源：https://doi.org/10.1186/s12943-024-01958-4 总之，本研究表明与CCL11融合抗原不仅增加了特异性CD8 + T细胞的数量，而且提高了T细胞的质量，表现为TCF1 + PD1- CD62L +干细胞样CD8 + T细胞的数量和克隆多样性的增加。同时，在肿瘤中诱导了一个由先天免疫细胞和特异性免疫细胞组成的肿瘤致死性微环境。机制研究表明，CCR3 +细胞参与了这些免疫增强作用。虽然需要进一步鉴定特定的CCR3 +亚群，但它也表明，有效的抗肿瘤疫苗需要多种细胞亚群的参与。（生物谷 Bioon.com）参考文献: Hailong Qi et al. Genetic fusion of CCL11 to antigens enhances antigenicity in nucleic acid vaccines and eradicates tumor mass through optimizing T-cell response. Mol Cancer. 2024 Mar 8;23(1):46. doi: 10.1186/s12943-024-01958-4.

信使RNA疫苗寡核苷酸免疫疗法

2024-03-08

·今日头条

零复发！实体瘤克星TCR-T疗法新增两款血液肿瘤产品，I期效果惊艳

据环球通讯社（Source: GlobeNewswire）报道，2024年2月26日，TScan Therapeutics生物制药公司，在ASTCT（即美国移植和细胞治疗学会）和CIBMTR（即国际血液和骨髓移植中心的移植和细胞治疗会议）串联会议上，公布了两款新的TCR-T疗法产品—— TSC-100和TSC-101的Ⅰ期最新临床研究数据（NCT05473910），旨在治疗残留病灶并预防造血干细胞移植（HCT）后复发的急性髓性白血病（AML）、急性淋巴细胞白血病（ALL）、骨髓增生异常综合征（MDS）患者，目前该公司在积极探索2期临床试验推荐剂量。既往TCR-T疗法的研发主要针对实体瘤，此次公布的这两款产品却对血液肿瘤重拳出击，为TCR-T疗法的研发及应用开辟了新的赛道！ ▲截图源自“FINANCIAL TIMES” TSC-100和TSC-101剑指血液肿瘤大约30%~40%的急性髓性白血病（AML）患者，在异基因造血干细胞移植（HCT）治疗后复发，使得这类患者的治疗选择较为局限。 TSC-100和TSC-101是同种异体供体来源的T细胞受体基因工程改造的T细胞（TCR-T），分别靶向 HA-1和HA-2造血细胞抗原，两者均呈递于HLA-A*02:01。该药通过选择HLA-A*02:01或HA-1阴性的供体，可选择性消除造血干细胞移植后，残留的患者造血细胞，并预防癌症复发（治病机理详见下图）。 ▲图源“Blood”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 TSCAN-001（NCT05473910）是一项多中心、多臂非随机、对照1期研究，目的是评估TSC-100和TSC-101的可行性、安全性和初步疗效。将入组的患有AML、MDS或ALL的成年患者分为两组，即治疗组（HLA-A*02:01和HA-1/HA-2阳性患者）、对照组（HLA-A*02:01阴性患者）。入组后，治疗组（8例）患者先接受HCT治疗，再接受TSC-100（4例）或TSC-101（4例）治疗；对照组患者仅接受HCT治疗（3例）。HCT随访后中位时间为111天（范围33-266天）。结果显示如下： 1、TSC-100治疗组（N=4：T-ALL、AML、AML、MDS：接受TSC-100治疗的全部4例患者，均完全的供体嵌合，且没有复发。 2、TSC-101治疗组（N=4：TP53突变MDS、AML、B-ALL、B-ALL）：接受TSC-101治疗的全部4例患者实现了完全供体嵌合，且没有复发。其中包括1例患有高危TP53突变的MDS ，在接受TSC-101治疗后，现已达到1年未复发的奇迹，具有里程碑氏的意义！因为随着时间的推移，复发的可能性显著降低，从而有助于改善生活质量。此外，1例在HCT治疗后呈MRD阳性的AML患者，在 TSC-101治疗后转为MRD阴性，并维持MRD阴性状态（最近一次测量是在第180天）。 TSC-100及TSC-101在给药后的所有监测时间点，均持续存在，且最长的随访时间超过9个月。此外，与单次给药（剂量水平1）相比，重复给药（剂量水平2和3）导致循环TSC-100和TSC-101水平增加3倍。综上，造血干细胞移植后，使用TSC-100/101靶向MiHAHA-1或HA-2，显示出早期安全性和有效性的生物标志物证据，从而降低复发风险。 TCR-T疗法血液肿瘤招募进行时目前正有两款研发的TCR-T疗法，在招募复发难治恶性血液病、复发/难治性EBV阳性淋巴瘤患者。此外，若想寻求其他细胞疗法（如CAR-T、TILs、CAR-NK、CTL、NK）帮助的患者，同样可将治疗经历、病理报告、出院小结等，提交至全球肿瘤医生网医学部初步评估病情。 TCR-T疗法全力打击多款实体瘤其实除了在研的这两款产品外，还有多款TCR-T产品值得期待，剑指胰腺癌、黑色素瘤、肉瘤等多款实体瘤，目前在研靶点详见下图。下面小编简单盘点一下其中的佼佼者，以供参考！ ▼早期TCR-T产品覆盖的肿瘤适应证 ▲图源“CorreGene”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 01 黑色素瘤克星-Kimmtrak，首款获批的TCR-T产品 2022年1月25日，首款TCR-T细胞产品—— Kimmtrak（IMCgp100，tebentafusp-tebn），获美国食品和药物管理局（FDA）批准，用于治疗成年不可切除或转移性葡萄膜黑色素瘤（HLA-A*02:01阳性）。 KIMMTRAK的获批是基于3期IMCgp100-202临床试验结果，该研究共入组378名HLA-A*02:01阳性转移性葡萄膜黑色素瘤患者，并将其随机分为两组（2:1），一组为KIMMTRAK组（N=252），接受Kimmtrak治疗；另一组为对照组（N=126），给予伊匹单抗、派姆单抗或达卡巴嗪治疗）。结果如下： 1、中位总生存期（OS）： 21.7个月（KIMMTRAK组）vs 16个月（对照组）； 2、中位无进展生存期（PFS）： 3.3个月（KIMMTRAK组）vs 2.9个月（对照组）； 3、1年总生存率： 73.2% （KIMMTRAK组）vs 58.5%（对照组）。总之，上述数据显示，与对照组相比，Kimmtrak单药治疗显著降低了葡萄膜黑色素瘤的病情进展或死亡风险，使其降低27%。 02 胰腺癌：TCR-T治疗部分缓解率高达72% 一例71岁进行性转移性胰腺癌患者，既往接受手术及放化疗后，病情持续进展，癌细胞已扩散至肺部。不过幸运的是。该患者基因检测发现，体内存在一种“KRAS”的突变蛋白，这也为该患者后续接受靶向KRASG12D的TCR-T治疗，提供了可能。患者入组后，见接受了托珠单抗+环磷酰胺的预处理治疗，之后再接受TCR-T治疗。结果显示，TCR-T治疗后第21天，患者的血小板计数和绝对中性粒细胞得以恢复；治疗第1个月的计算机断层扫描显示，患者肺转移病灶消退；治疗后6个月，部分缓解（PR）率高达72%！图1 胰腺癌患者TCR-T治疗前后，胸部计算机断层扫描对比图 ▲图源“NEJM”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 03 乙肝病毒相关肝细胞癌：SCG101具有抗癌及抗病毒双重功效 ▲图源“NMPA官网” SCG101是由星汉德生物公司研发的一款TCR-T细胞产品，并在2022年3月，获中国国家药品监督管理局（NMPA）新药IND批准。 SCG101是一种乙肝抗原特异性的TCR-T细胞疗法，既能有效清除HBV-HCC肿瘤细胞、HBV-DNA整合的癌前病变细胞，达到“抗癌”的效果；同时还能清除HBV感染细胞，实现抗病毒的功效，可谓“一箭双雕”！一项关于“ SCG101治疗乙型肝炎病毒（HBV）相关肝细胞癌（HCC） ”的临床研究，共纳入1例HBV相关的肝细胞癌患者，入组后仅接受单剂SCG101输注，而未接受其他抗肿瘤治疗，结果显示如下： 1、肿瘤缓解：患者在治疗第28天，达到部分缓解（PR），肿瘤靶病灶相比基线缩小66% ，并在治疗第4个月进一步缩小至74.5% ；同时另一处病灶完全消失。截至数据统计时，该患者肿瘤未进展时间已超过6.9个月。图2 HBV相关肝细胞癌患者，回输SCG101前后影像学变化 ▲图源“CISION”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 2、HBV感染缓解：该患者在回输SCG101前后，肝脏免疫组化结果显示，乙肝表面抗原阳性肝细胞达到100%清除； HBsAg（HBV血清学标志）水平，也从治疗前的557.96 IU/mL，下降至1.3 IU/mL（回输SCG101第7天）、 0.08 IU/mL （回输第28天）。图3 回输SCG101前后，HBsAg值变化 ▲图源“CISION”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除如何寻求个性化癌症疫苗帮助目前正有几款TCR-T疗法，在招募乙型肝炎病毒相关肝细胞癌、妇科恶性肿瘤（卵巢癌、子宫内膜癌、宫颈癌）、头颈部肿瘤等患者开展临床试验。 04 滑膜肉瘤：TAEST16001初战告捷，疾病控制率达83.3% TAEST16001是由我国香雪生命科学技术公司自主研发的一款TCR-T细胞产品，TAEST16001治疗晚期软组织肉瘤的Ⅰ期临床试验结果惊艳！本次研究共纳入12例 HLA-A*02:01阳性且表达NY-ESO-1的晚期软组织肉瘤患者（滑膜肉瘤10例，脂肪肉瘤2例）。58.3%（7/12）为男性，，中位年龄为33（25-67）岁。此外，83.3%的患者既往至少接受过2种化学药物治疗。入组后，在给予改良淋巴细胞清除术后，输注TAEST16001细胞治疗。经过为期43天的中位随访，结果显示： 1、缓解时间：中位缓解时间（TTR）为1.9个月，中位缓解持续时间为13.1个月。 2、客观缓解率（ORR）： ORR为41.7% （95%CI，15.2–72.3）。 3、部分缓解（PR）率：12例患者中有 5例获得部分缓解，PR率为41.67%。 4、疾病控制率：5例[41.7%（95%CI，15.2–72.3）]患者疾病稳定，疾病控制率为83.3% （95%CI，51.6–97.9）。 5、中位无进展生存期（PFS）： PFS为7.2个月（95%CI，2.5–11.8）。综上，9例（75%）患者显示肿瘤消退，6例（50%）患者在第一次放射学评估后肿瘤负荷持续下降。让我们期待这款TCR-T疗法的后续临床研究成果！图4 单个可评估患者的最佳临床反应 ▲图源“Cell Rep Med”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除我国TCR-T研发全面开花，精准打击多款癌种！截至目前，TCR-T细胞免疫疗法已在部分实体肿瘤治疗中，取得了较满意的疗效，尤其是对黑素瘤、肝癌、滑膜细胞肉瘤等实体瘤的治疗效果较为明显。作为细胞免疫治疗的热门赛道之一，TCR-T细胞治疗产品已吸引了多家药企布局，目前我国也有多款TCR-T产品新药IND获批，期待能早日迎来我国自主研发的TCR-T上市的好消息！ 1 TC-N201注射液 ▲图源“NMPA官网” 2022年11月28日，由广东天科雅生物医药科技公司研发的一款TCR-T产品——“TC-N201注射液”的临床试验申请（IND），获国家药监局审查中心批准，用于治疗既往治疗失败的复发或者转移性实体瘤（LA-A2和NY-ESO-1阳性）。 2 TAEST1901 ▲图源“NMPA官网” 2022年4月20日，由香雪生命科学研发的一款创新型TCR-T产品——“TAEST1901注射液”，获中国国家药监局（NMPA）的临床试验许可，拟用于治疗晚期肝癌或其它晚期肿瘤（HLA-A*02:01、肿瘤抗原AFP表达阳性）。 3 CRTE7A2-01 ▲图源“NMPA官网” 2023年8月25日，北京可瑞生物科技有限公司研发的一款TCR-T细胞注射液——“CRTE7A2-01”的临床新药IND获国家药品审评中心批准，拟用于治疗头颈部肿瘤、HPV16阳性晚期宫颈癌等多款实体瘤。研究显示，CRTE7A2-01有良好的抗肿瘤活性，可通过靶向抑制HPV16 E7突变的表达，防治细胞向恶性方向转化。此前该药已通过FDA临床申请（NCT05122221），预计将于2024年11月完成I期试验。小编寄语 TCR-T疗法作为一种新型的抗肿瘤方案，具有归巢能力强、安全性良好等优点，在黑色素瘤、非小细胞肺癌、肝癌、滑膜肉瘤等多款实体瘤治疗领域，取得了不俗的成绩。本次随着TSC-100和TSC-101Ⅰ期临床结果的公布，也让我们看到了TCR-T疗法在血液肿瘤领域的应用潜力。各国对TCR-T疗法的研发热度持续攀升，我国包括来恩生物、星汉德、百吉生物、香雪生命、天科雅等多家企业也已进入到临床研究阶段，目前最快已推进到2期临床研究阶段，我们也期望未来会有越来越多的TCR-T细胞产品问世，造福更多的患者！参考资料 [1]Al Malki M M,et al.Initial Results of a Phase 1 Trial of TSC-100 and TSC-101, Engineered T Cell Therapies That Target Minor Histocompatibility Antigens to Prevent Relapse after Allogeneic Hematopoietic Cell Transplantation[J].Blood,2023,142:2090. https://ashpublications.org/blood/article/142/Supplement+1/2090/500034/Initial-Results-of-a-Phase-1-Trial-of-TSC-100-and [2]Nayar R,et al. 156 Discovery of TSC-100: A natural HA-1-specific TCR to treat leukemia following hematopoietic stem cell transplant therapy[J]. 2020. https://jitc.bmj.com/content/8/Suppl_3/A94 [3]Pan Q,et al.Phase 1 clinical trial to assess safety and efficacy of NY-ESO-1-specific TCR T cells in HLA-A∗02:01 patients with advanced soft tissue sarcoma. Cell Rep Med. 2023 Aug 15;4(8):101133. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439245/ [4]https://markets.ft.com/data/announce/full?dockey=1330-9052919en-62GP5TO6D9ULFSTC04EREDQ9VU [5]https://corregene.com/index.php?m=content&c=index&a=lists&catid=10 [6]https://hk.prnasia.com/story/406654-2.shtml [7]https://www.nejm.org/doi/full/10.1056/NEJMoa2119662 [8]https://www.cde.org.cn/ 本文为全球肿瘤医生网原创，未经授权严禁转载

细胞疗法临床2期临床结果临床终止

2024-03-01

·BioSpace

Defence Announces Peer-Reviewed Publication on Accum-E7 Anti-Cancer Vaccine in Cancer Science Journal and Financing Update

Vancouver, British Columbia--(News - February 29, 2024) - Defence Therapeutics Inc. (CSE: DTC) (OTCQB: DTCFF) (FSE: DTC) ("Defence" or the "Company"), one of the leading Canadian biotechnology companies working in the field of immune-oncology, is pleased to announce the publication of a peer-reviewed study on the anticancer properties of its dual Accum®-E7 vaccine, one of Defence's experimental product designed to treat established cervical cancer. The study, which was published in the prestigious journal of Cancer Science, is entitled, "An engineered Accum®-E7 protein-based vaccine with dual anti-cervical cancer activity", and can be directly accessed at the following address . The human papillomavirus (HPV) can cause genital warts subsequently leading to cervical, anal, or head and neck cancers. Prophylactic HPV vaccines were therefore developed to prevent these infections and their associated complications. The most widely used of all four commercially available HPV vaccines is Gardasil-9®. However, this vaccine has challenges: it requires three doses and the vaccine manufacturing remains costly, which may be prohibitive to low-income countries. In addition, the vaccine cannot provide complete protection against all 14 high-risk HPV subtypes as it only targets 9 of them. Furthermore, the vaccine should be administered before HPV exposure implying that it cannot treat existing infections or established cervical cancer. The peer-reviewed study on Defence's Accum®-E7 anti-cancer vaccine presents an engineered Accum®-E7 protein-based vaccine capable of providing a durable memory response when used prophylactically. In addition, the selection of E7 as a target "non-self" antigen widened the vaccine scope of application as it can also control the growth of pre-established cervical tumors through the generation of potent cytotoxic T lymphocytes (CTLs). "Overall, this engineered Accum®-E7 vaccine is safe, simple to engineer and manufacture making it an elixir candidate capable of providing both prophylactic and therapeutic activity against cervical cancer," says Dr. Rafei, the Chief Scientific Officer of Defence Therapeutics. The key highlights of the Accum®-E7 study are: Prophylactic vaccination using the Accum®-E7 vaccine confers complete protection despite multiple challenges. Accum®-E7 elicits antibodies capable of interfering with cancer cell proliferation in vitro. Therapeutic vaccination using Accum®-E7 synergises with multiple immune-checkpoint inhibitors. The therapeutic effect of Accum®-E7 relies on cross-presenting dendritic cells (DCs) and CD8 T cells. Vaccination using Accum®-E7 is safe and immunogenic as shown in the conducted GLP study. "This prestigious peer-reviewed publication provides an additional example of how the Accum® technology can be exploited in the development of vaccines. It also opens up a new line of investigations where Defence's more potent Accum® variants could be tested as bioconjugates to protein antigens," said Mr. Plouffe, Chief Executive Officer of Defence Therapeutics. In summary, our study shows that Accum®-E7: i) provides potent protection (prophylactic vaccination) and durable memory responses, ii) triggers antibodies exhibiting a non-negligible role in fighting cervical tumors, iii), controls established tumors when delivered in combination with several immune-checkpoint inhibitors (therapeutic vaccination), and iv) is relatively safe, well tolerated and immunogenic by animals even when used at higher doses (GLP study). Financing Update The Company also provides an update to its previously announced non-brokered private placement of up to 1,500,000 units of the Company (each a "Unit") at a price of $1.50 per Unit for gross proceeds of up to $2,250,000 (the "Offering"). Following the first tranche closing of 567,000 Units for aggregate proceeds of $850,500 on January 30th, 2024, the Company has received a 45-day extension from the Canadian Securities Exchange to complete the Offering. About Defence: Defence Therapeutics is a publicly-traded biotechnology company working on engineering the next generation vaccines and ADC products using its proprietary platform. The core of Defence Therapeutics platform is the ACCUM® technology, which enables precision delivery of vaccine antigens or ADCs in their intact form to target cells. As a result, increased efficacy and potency can be reached against catastrophic illness such as cancer and infectious diseases. For further information: Sebastien Plouffe, President, CEO and Director P: (514) 947-2272 Splouffe@defencetherapeutics.com Cautionary Statement Regarding "Forward-Looking" Information This release includes certain statements that may be deemed "forward-looking statements". All statements in this release, other than statements of historical facts, that address events or developments that the Company expects to occur, are forward-looking statements. Forward-looking statements are statements that are not historical facts and are generally, but not always, identified by the words "expects", "plans", "anticipates", "believes", "intends", "estimates", "projects", "potential" and similar expressions, or that events or conditions "will", "would", "may", "could" or "should" occur. Although the Company believes the expectations expressed in such forward-looking statements are based on reasonable assumptions, such statements are not guarantees of future performance and actual results may differ materially from those in the forward-looking statements. Factors that could cause the actual results to differ materially from those in forward-looking statements include regulatory actions, market prices, and continued availability of capital and financing, and general economic, market or business conditions. Investors are cautioned that any such statements are not guarantees of future performance and actual results or developments may differ materially from those projected in the forward-looking statements. Forward-looking statements are based on the beliefs, estimates and opinions of the Company's management on the date the statements are made. Except as required by applicable securities laws, the Company undertakes no obligation to update these forward-looking statements in the event that management's beliefs, estimates or opinions, or other factors, should change. Neither the CSE nor its market regulator, as that term is defined in the policies of the CSE, accepts responsibility for the adequacy or accuracy of this release. To view the source version of this press release, please visit

疫苗免疫疗法