A Phase 2 Study of the Safety, Efficacy, and Immune Response of CRS-207, Pembrolizumab, Ipilimumab, and Tadalafil in Patients With Previously Treated Metastatic Pancreatic Adenocarcinoma

The purpose of this study is to evaluate the safety and clinical activity of tadalafil, pembrolizumab, ipilimumab, and CRS-207 in subjects with metastatic pancreatic adenocarcinoma who have progressed after at least 1 prior chemotherapy regimen.

开始日期2022-08-22

申办/合作机构

The Sidney Kimmel Comprehensive Cancer Center

[+2]

NCT03006302 / Active, not recruiting临床2期IIT

Phase 2 Study of Epacadostat, Pembrolizumab, and CRS-207, With or Without Cyclophosphamide and GVAX Pancreas Vaccine in Patients With Metastatic Pancreas Cancer

This study will enroll patients who have metastatic pancreatic cancer and have progressed on prior chemotherapy.
Part 1 (dose escalation) participants will receive epacadostat/pembrolizumab/cyclophosphamide(CY)/GVAX pancreas vaccine followed by epacadostat/pembrolizumab/CRS-207, Part 1X (dose escalation) participants will receive epacadostat/pembrolizumab/CRS-207. Part 2X (dose expansion) participants will receive epacadostat/pembrolizumab/CRS-207.
The primary objectives of this study are to determine the recommended dose of epacadostat in this combination and assess survival of subjects in both treatment groups.

开始日期2018-01-31

申办/合作机构

The Sidney Kimmel Comprehensive Cancer Center

[+2]

NCT03190265 / Completed临床2期IIT

A Randomized Phase 2 Study of the Safety, Efficacy, and Immune Response of CRS-207, Nivolumab, and Ipilimumab With or Without GVAX Pancreas Vaccine (With Cyclophosphamide) in Patients With Previously Treated Metastatic Pancreatic Adenocarcinoma

The purpose of this study is to study the safety and clinical activity of nivolumab and ipilimumab in combination with either sequential administration of CY/GVAX pancreas vaccine followed by CRS-207 (Arm A) or with administration of CRS-207 alone (Arm B) in patients with pancreatic cancer.

开始日期2017-12-14

申办/合作机构

The Sidney Kimmel Comprehensive Cancer Center

[+3]

100 项与 CRS-207 相关的临床结果

登录后查看更多信息

100 项与 CRS-207 相关的转化医学

登录后查看更多信息

100 项与 CRS-207 相关的专利（医药）

登录后查看更多信息

项与 CRS-207 相关的文献（医药）

2020-07-15·Clinical cancer research : an official journal of the American Association for Cancer Research1区 · 医学

Evaluation of Cyclophosphamide/GVAX Pancreas Followed by Listeria-Mesothelin (CRS-207) with or without Nivolumab in Patients with Pancreatic Cancer.

1区 · 医学

Article

作者: Takahiro Tsujikawa ; Todd Crocenzi ; Jennifer N Durham ; Elizabeth A Sugar ; Annie A Wu ; Beth Onners ; Julie M Nauroth ; Robert A Anders ; Elana J Fertig ; Daniel A Laheru ; Kim Reiss ; Robert H Vonderheide ; Andrew H Ko ; Margaret A Tempero ; George A Fisher ; Michael Considine ; Ludmila Danilova ; Dirk G Brockstedt ; Lisa M Coussens ; Elizabeth M Jaffee ; Dung T Le

PURPOSE:

Two studies in previously-treated metastatic pancreatic cancer have been completed combining GVAX pancreas vaccine (granulocyte-macrophage colony-stimulating factor-secreting allogeneic pancreatic tumor cells) with cyclophosphamide (Cy) and CRS-207 (live, attenuated Listeria monocytogenes expressing mesothelin). In the current study, we compared Cy/GVAX followed by CRS-207 with (Arm A) or without nivolumab (Arm B).

EXPERIMENTAL DESIGN:

Patients with pancreatic adenocarcinoma who received one prior therapy for metastatic disease and RECIST measurable disease were randomized 1:1 to receive treatment on Arm A or Arm B. The primary objective was to compare overall survival (OS) between the arms. Additional objectives included assessment of progression-free survival, safety, tumor responses, CA19-9 responses and immunologic correlates.

RESULTS:

Ninety-three patients were treated (Arm A, 51; Arm B, 42). The median OS in Arms A and B were 5.9 (95% CI, 4.7, 8.6) and 6.1 (95% CI, 3.5, 7.0) months, respectively, with a hazard ratio 0.86 (95% CI, 0.55, 1.34). Objective responses were seen in three patients using immune-related response criteria (4%, 2/51, Arm A; 2%, 1/42, Arm B). The > grade 3 related adverse event rate while higher in Arm A (35.3% vs 11.9%) was manageable. Changes in the microenvironment, including increase in CD8⁺ T cells and a decrease in CD68⁺ myeloid cells, were observed in long-term survivors in Arm A only.

CONCLUSIONS:

While the study did not meet its primary endpoint of improvement in OS of Arm A over Arm B, the OS was comparable to standard therapy. Objective responses and immunologic changes in the tumor microenvironment were evident.

2020-05-01·Cancer immunology research1区 · 医学

Single-Cell Immune Competency Signatures Associate with Survival in Phase II GVAX and CRS-207 Randomized Studies in Patients with Metastatic Pancreatic Cancer.

1区 · 医学

Article

作者: Nitya Nair ; Shih-Yu Chen ; Ed Lemmens ; Serena Chang ; Dung T Le ; Elizabeth M Jaffee ; Aimee Murphy ; Chan Whiting ; Thomas Müller ; Dirk G Brockstedt

The identification of biomarkers for patient stratification is fundamental to precision medicine efforts in oncology. Here, we identified two baseline, circulating immune cell subsets associated with overall survival in metastatic pancreatic cancer patients who were enrolled in two phase 2 randomized studies of GVAX pancreas and CRS-207 immunotherapy. Single-cell mass cytometry was used to simultaneously measure 38 cell surface or intracellular markers in peripheral blood mononuclear cells obtained from a phase 2a patient sub-cohort (N=38). CITRUS, an algorithm for identification of stratifying subpopulations in multidimensional cytometry datasets, was used to identify single-cell signatures associated with clinical outcome. Patients with a higher abundance of CD8+CD45RO-CCR7-CD57+ cells and a lower abundance of CD14+CD33+CD85j+ cells had improved overall survival (median OS, range (days) 271, 43-1247) compared to patients with a lower abundance of CD8+CD45RO-CCR7-CD57+ cells and higher abundance of CD14+CD33+CD85j+ cells (77, 24-1247 days; P=0.0442). The results from this prospective-retrospective biomarker analysis were validated by flow cytometry in 200 pancreatic cancer patients enrolled in a phase 2b study (P=0.0047). The identified immune correlates provide potential prognostic or predictive signatures that could be employed for patient stratification.

2019-10-01·Clinical cancer research : an official journal of the American Association for Cancer Research1区 · 医学

Clinical Response of Live-Attenuated, Listeria monocytogenes Expressing Mesothelin (CRS-207) with Chemotherapy in Patients with Malignant Pleural Mesothelioma.

1区 · 医学

Article

作者: Raffit Hassan ; Evan Alley ; Hedy Kindler ; Scott Antonia ; Thierry Jahan ; Somayeh Honarmand ; Nitya Nair ; Chan C Whiting ; Amanda Enstrom ; Ed Lemmens ; Takahiro Tsujikawa ; Sushil Kumar ; Gina Choe ; Anish Thomas ; Katherine McDougall ; Aimee L Murphy ; Elizabeth Jaffee ; Lisa M Coussens ; Dirk G Brockstedt

PURPOSE:

Malignant pleural mesothelioma (MPM) is an aggressive cancer associated with poor prognosis. CRS-207 is a live-attenuated Listeria monocytogenes engineered to express mesothelin, a tumor-associated antigen highly expressed in MPM. CRS-207 induces antitumor immune responses and increases susceptibility of neoplastic cells to immune-mediated killing.

PATIENTS AND METHODS:

Patients with unresectable MPM, ECOG 0 or 1, and adequate organ and pulmonary function were enrolled in this multicenter, open-label phase Ib study. They received two priming infusions of 1 × 10⁹ CFU CRS-207, followed by pemetrexed/cisplatin chemotherapy, and CRS-207 booster infusions. Primary objectives were safety and induction of immune response. Secondary/exploratory objectives included tumor response, progression-free survival (PFS), overall survival (OS), immune subset analysis, and gene-expression profiling of tumor.

RESULTS:

Of 35 evaluable patients, 89% (31/35) had disease control with one complete response (3%), 19 partial responses (54%), and 10 stable disease (29%). The estimated median duration of response was 5.0 months (95% CI, 3.9-11.5). The median PFS and OS were 7.5 (95% CI, 7.0-9.9) and 14.7 (95% CI, 11.2-21.9) months, respectively. Tumor size reduction was observed post-CRS-207 infusion prior to chemotherapy in 11 of 35 (31%) patients. No unexpected treatment-related serious adverse events or deaths were observed. IHC analysis of pre- and post-CRS-207 treatment tumor biopsies revealed possible reinvigoration and proliferation of T cells, increased infiltration of dendritic and natural killer cells, increased CD8:T_reg ratio, and a shift from immunosuppressive M2-like to proinflammatory M1-like macrophages following CRS-207 administration.

CONCLUSIONS:

Combination of CRS-207 and chemotherapy induced significant changes in the local tumor microenvironment and objective tumor responses in a majority of treated patients.

项与 CRS-207 相关的新闻（医药）

2024-01-03

·药渡Daily

2023年ADC领域重磅交易盘点：中国Biotech与MNC的双向奔赴

纵观2023年的创新药BD交易，ADC药物从年头火到年尾，引领中国创新药的出海高潮，交易次数多达20余起，总计交易金额超200亿美元。统计出手次数、首付款金额、总金额，BioNTech、GSK、阿斯利康和BMS这4家跨国药企表现最为亮眼，早早出手将心仪的ADC收入囊中。目前出海的ADC大多处于早期临床，MNC各自选择在差异化方面布局，通过不同的新组合抢占市场。图片来源：药渡数据、作者整理BioNTech寻求下一个盈利点，疯狂扫货中国Biotech2020年，成立12年的BioNTech凭借mRNA新冠疫苗在商业化上的成功，完成了超强的原始资本积累。然而，疫情退却，BioNTech的收入大幅下滑，手握重金的BioNTech开始寻求新的收入来源，寻找潜在合作项目扩充研发管线。仅2023年，BioNTech与5家中国Biotech达成合作，引进8个新分子，其中包括4款ADC产品，披露的总金额为37.25亿美元，成为中国Biotech最大买家。回顾今年BioNTech的引进交易，获取授权的4个ADC分子涉及的靶点包括HER2、HER3、Trop2、B7H3。BioNTech选择这几个产品的可能有以下几个理由：这些靶点是ADC领域研究相对成熟的靶点，有大量的临床前和临床数据支撑，相较于其他研究冷门的ADC靶点临床开发率失败率较低；BioNTech在引进这4个ADC分子时，只有Trop2 ADC处于临床II期，其余几个分子均处于I期或临床前阶段，在全球范围内进展并不靠前，BioNTech能够以较低底价拿到biotech的重点创新型产品。这几个靶点均覆盖较大的适应症，在乳腺癌、肺癌等多个大癌种均具备巨大开发潜力。但是，拿HER2这一靶点来说，前有Enhertu这样的重磅产品“珠玉在前”，又有RC48紧跟其后，未来上市的HER2 ADC产品能够在市场上占有多大份额还很是个未知数。阿斯利康扩张ADC版图，重金押注下一个Enhertu在ADC领域，阿斯利康可谓是眼光独到，早在2013年，阿斯利康开始涉足ADC领域，在2019年凭借Enhertu的大火直接跃升到ADC第一梯队。根据阿斯利康公布2023H1业绩显示，Enhertu销售额增长翻倍，上半年实现5.8亿美元销售额。目前，第一三共和阿斯利康还在全球开展多项临床试验，评估Enhertu单药和联合疗法在多种HER2靶向癌症中的疗效和安全性。未来，Enhertu有望实现百亿美元销售额。图片来源：阿斯利康2023H1财报在携手第一三共开发Enhertu大获成功之后，阿斯利康不断推进ADC管线布局，自研与引进并重。阿斯利康目前的研发管线中已积累了超10余款在研ADC产品，涉及的靶点不仅包括HER2和Trop2等热门靶点，还包括FRα和B7H4等具有差异化的靶点。不难看出，阿斯利康已将ADC将作为夯实其肿瘤业务业绩增长的重要板块之一。随着中国ADC赛道不断成熟，阿斯利康开始把目光投向国内，在今年上半年分别引进了康诺亚/乐普生物的CMG901和礼新医药的LM-305两款ADC产品。与BioNTech不同，阿斯利康选择的是更具有差异化的靶点。CMG901是一款全球首创的靶向Claudin 18.2的抗体偶联药物，2022年9月，CMG901获CDE授予突破性治疗药物认定，用于治疗经一线及以上治疗失败或不能耐受的Claudin 18.2阳性晚期胃癌。LM-305是一款靶向GPRC5D的抗体偶联药物，作为针对复发/难治性骨髓瘤的潜在新疗法，丰富了阿斯利康在血液瘤产品管线。所谓“技多不压身”，有钱有实力，阿斯利康在ADC领域的未来还是值得期待的。GSK重振旗鼓，再战ADC曾经的疫苗之王葛兰素史克（GSK）,在新冠疫苗研发竞速中错失良机。2016年重回肿瘤领域后也几经受挫，其PD-1产品Jemperli销售不及预期，肿瘤管线中的支柱产品Zejula也存在安全性问题。GSK也曾想尝试在ADC市场分一杯羹，开发推出首款BCMA ADC，但由于验证性临床试验失败而撤市。2022年，与Mersana合作的HER2 STING产品XMT-2056也因严重不良事件暂停临床试验。GSK并未放弃希望，仍在市场上物色新对象，希望在本轮的ADC浪潮中押宝成功，以拉升肿瘤领域。2023年10月，GSK宣布以15.7亿美元的总金额引进了翰森制药的B7H4 ADC（HS-20089），12月，又与翰森制药签订B7H3 ADC（HS-20093）药物的许可协议，里程碑付款最多达15.25亿美元，累计交易最大金额已经超过30多亿美元，足见GSK布局ADC领域的决心。对于B7H4靶点，目前尚未有ADC成药，在全球同靶点管线中，仅有翰森的HS-20089进入临床2期，且已经在三阴性乳腺癌上看到了成药的潜力。临床进展最快，且拥有成药潜力或许是打动GSK最主要原因。2023年，翰森在ASCO公布了B7H3 ADC（HS-20093）在晚期实体瘤中的I期研究数据，在小细胞肺癌中数据，HS-20093的ORR（客观缓解率）为63.6%，DCR（疾病控制率）为81.8%，中位PFS（无进展生存期）为4.7个月，3个月无进展生存率为72.7%。良好的初步研究数据，HS-20093在小细胞肺癌上的治疗潜力无疑是吸引GSK拿下这款在研管线的重要原因。图片来源：2023 ASCO放弃肿瘤领域，又重新加入战场，两度牵手翰森，重金押注，切入ADC赛道。GSK的选择可以说既理性又勇敢。BMS应对“专利悬崖”，开启“买买买”模式百时美施贵宝（BMS）在2023年发布的第三季度财报中，其在美国的销售收入连续第五季度下降。下降主要归因于肿瘤业务王牌产品来那度胺的专利悬崖到来；且在商业化方面PD-1抗体O药销售增长势头也日益趋弱，不及默沙东的K药。早在2007年，BMS为了应对专利悬崖，就开始通过收购和联合开发的战略方式，寻找下一个重磅产品。随着ADC药物的爆火，ADC领域一定是BMS未来战略发展的重要一环。2023年接近尾声之际，BMS用8亿美元首付款，84亿美元的总金额引进百利天恒的BL-B01D1，一款靶向HER3/EGFR的双抗ADC。该交易创下了2023年国产创新药license out总金额之最，也刷新了我国创新药授权出海首付款新纪录；BL-B01D1也是我国首款成功出海的双抗ADC新药。根据披露的I期临床试验结果显示，BL-B01D1与第一三共的HER3 ADC U3-1402不相上下，但相比于U3-1402，BL-B01D1还有拓展更多适应症的可能性以及更大的市场空间。BL-B01D1单药在未来有很大可能获批末线NSCLC；并且可以联合“O药”去冲1线。对于手握“O药”的BMS来说，不仅看重其单药的用药潜力，更加关注与PD-1联用的潜力。数据来源：2023 ASCO但不可忽略新药从研发、临床推到上市的时间成本，BL-B01D1仅是一款处于临床I期的在产品，存在极大的不确定性。而BMS的“O”药预计2028年面临专利期风险，留给PD-1+ADC的研发时间还是相当紧张的。辉瑞豪掷重金，拿ADC赌明天面临专利悬崖危机的MNC不止BMS一家。有“宇宙第一大药厂“之称的辉瑞到2030年将有11款重要药物失去专利保护，并且随着疫情发展”红利“褪去，辉瑞凭借mRNA疫苗创下的千亿美元的营收战绩也急剧跳水。尽管辉瑞也是最早布局ADC药物的玩家，但其2款产品ADC产品Mylotarg（靶向CD33）和Besponsa（靶向CD22）的市场销售并不及预期。为了寻找下一个业绩爆点，2023年3月，辉瑞以430亿美元天价收购Seagen，加速布局ADC赛道。在豪掷重金收购“ADC先驱”Seagen后，辉瑞又盯上了中国ADC产品。2023年12月，辉瑞与和铂医药达成了全球权益合作，就其MSLN靶向抗体偶联药物（ADC）HBM9033的全球临床开发和商业化达成独家许可协议，交易总额可高达约11亿美元。HBM9033全人源单克隆抗体（mAb）由和铂医药专有HarbourMice平台产生，采用宜联生物最新一代TMALIN®ADC平台技术。临床前数据显示，HBM9033在体内研究中表现出卓越的药效性和安全性。靶点差异化，技术平台价值，使HBM9033成为全球一款潜在BIC产品。前尚无靶向MSLN的药物获批上市，但全球范围内不少制药巨头相继开展了MSLN药物的研发，包括拜耳的Anetumab ravtansine、Cerus Corp的CRS-207，以及国内荣昌生物的RC-88，可见此靶点的潜力，因此对于手持巨款的辉瑞来说自然不会错过开发此靶点的良机。目前获批的ADC产品仍是少数，赛道仍是一片蓝海。长期以来，国内药物创新虽然仍以me-too为主， Biotech的优势是早期的开发能力，但是在临床资源的布局、商业销售能力上与全球化药企有差别，所以寻求出海，找到雄厚资源的合作伙伴成为Biotech最佳选择。这也要求合作伙伴需要具备较强的临床能力，有较为丰富的资金储备，且对美国市场的报批流程较为较熟悉，并且具有一定的商业化能力。对于海外大药企而言，中国的ADC产品与其自身管线战略布局高度契合，能够填补产品组合空缺；通过license in可以很大程度节约研发的时间成本，博取未来更广阔的市场空间。当Biotech实力足够强的时候，就可以选择自己去独立进行临床试验，建立自己的商业化团队，最终实现本土ADC真正的“出海”。2023已经结束，2024，ADC的辉煌未完待续……参考资料BL-B01D1, a first-in-class EGFRxHER3 bispecific antibody-drug conjugate (ADC), in patients with locally advanced or metastatic solid tumor: Results from a first-in-human phase 1 study.

抗体药物偶联物财报引进/卖出疫苗临床2期

2023-02-17

·生物谷

《科学·转化医学》：让癌细胞“窝里斗”！哈佛团队将癌细胞改造成抗癌杀手，能诱导强力的抗肿瘤免疫

研究团队使用了人源GBM细胞系构建了hThTC1，并在人源化小鼠上测试了其治疗效果。结果显示，在切除原位肿瘤后，注射hThTC能够有效抑制复发肿瘤的生长并显著延长小鼠的生存期。这代表着活肿瘤细胞疫苗具疫苗，是免疫学赋予人类最强大的武器之一，拥有疫苗之后，许多传染病的流行得到有效控制，天花也已经绝迹。而现在，科学家们希望用这个武器来对付肿瘤。肿瘤在发生发展的过程中积累了多种突变，其中一些突变会引起蛋白质序列的变化，也就是所谓的肿瘤新抗原。免疫系统可以识别其中一些抗原，从而对肿瘤发动攻击，这使得学界萌生了使用肿瘤新抗原疫苗增强机体抗肿瘤免疫应答的想法。但是在既往的临床试验中，使用灭活肿瘤细胞进行免疫接种，并未给患者带来足够的临床获益[1-3]，因此还需进一步改良。近期，由哈佛医学院布莱根妇女医院干细胞和转化免疫治疗中心Khalid Shah领衔的研究团队在《科学·转化医学》上发表最新研究成果[4]：研究者在体外对肿瘤细胞进行改造，敲除IFN-β受体（IFNAR1），并使其过表达IFN-β和GM-CSF，再将经过改造的肿瘤细胞输回荷瘤小鼠体内，被改造后的肿瘤细胞能够抵达肿瘤病灶，并诱导强力的抗肿瘤免疫应答，显著延长了荷瘤小鼠的生存期。论文首页截图曾有研究将肿瘤细胞灭活后作为疫苗使用，但是灭活的肿瘤细胞失去归巢至体内病灶处的能力，并且也失去了表达蛋白质与递呈抗原给CD8+T细胞的能力，这意味着灭活肿瘤细胞疫苗难以在肿瘤病灶处激起足够强大的细胞免疫应答。因此，Khalid Shah研究团队决定开发一款基于活细胞的肿瘤细胞疫苗。研究者选用了恶性程度高的脑胶质母细胞瘤（GBM）作为测试模型，首先在体外对GBM细胞系CT2A进行改造，使其分泌能够改造肿瘤微环境的IFN-β和能够诱导DC细胞的GM-CSF，同时为了避免自我损伤，敲除了肿瘤细胞上的IFNAR1，被改造后的肿瘤细胞被称为ThTC。在体外共培养试验中，ThTC能直接杀伤未经改造的GBM细胞，说明ThTC可以凭借其分泌的IFN-β直接发挥抗肿瘤作用。 ThTC可以直接抑制肿瘤细胞的生长为了评估ThTC细胞能否在体内发挥抗肿瘤作用，研究团队构建了原位GBM小鼠模型，结果显示，接受ThTC免疫的小鼠，在接种WT GBM肿瘤细胞后，脑中没有形成可见的肿瘤，并且没有小鼠因为脑肿瘤死亡。这说明ThTC的直接抗肿瘤作用以及诱导抗肿瘤免疫作用最终完全消除了肿瘤。研究团队又给第一次荷瘤后幸存的小鼠对侧大脑再次接种肿瘤，观察小鼠是否具有免疫记忆，如能排除再次接种的肿瘤，则说明ThTC可以诱导免疫记忆。结果显示，接受ThTC治疗的小鼠完全消除了再次接种的肿瘤，而如果清除小鼠的CD4+T细胞，免疫记忆就无法形成，表明ThTC治疗可诱导对肿瘤的免疫记忆，且免疫记忆的形成依赖于CD4+T细胞。 ThTC治疗能完全清除肿瘤，并诱导T细胞免疫记忆接下来，研究团队为接种GBM的小鼠进行手术，切除瘤灶之后再给予小鼠ThTC治疗，从而在更贴近临床实际情况的状态下，评估ThTC治疗的价值。结果显示，接受ThTC治疗的小鼠复发率更低，生存期显著延长；对肿瘤浸润免疫细胞进行检测发现，接受ThTC治疗的小鼠肿瘤部位浸润的免疫细胞数量显著增加。转录组测序分析表明，接受ThTC治疗后，肿瘤中Ⅰ型干扰素通路、抗原递呈通路基因和免疫刺激性分子表达均明显上调。这些数据表明，ThTC治疗重塑了肿瘤免疫微环境，使其更偏向抗肿瘤免疫应答。 ThTC可降低肿瘤复发率并重塑肿瘤免疫微环境接下来研究团队测试了活肿瘤细胞疫苗在其他肿瘤中的效果，如针对肺癌的LLC-ThTC：结果显示，接种LLC-ThTC有效地抑制了肺癌进展，并显著延长了小鼠的生存期；在幸存小鼠的脑中再次接种肿瘤，模拟肺癌脑转移时，先前接受过LLC-ThTC免疫的小鼠能再次有效清除肿瘤。这表明，ThTC有望用于治疗多种肿瘤，并有效抑制肿瘤转移和复发。 LLC-ThTC不仅能够抑制原位肺癌生长，还能够帮助机体抵御脑转移瘤为了将上述小鼠中的发现转化到临床场景，研究团队使用了人源GBM细胞系构建了hThTC1，并在人源化小鼠上测试了其治疗效果。结果显示，在切除原位肿瘤后，注射hThTC能够有效抑制复发肿瘤的生长并显著延长小鼠的生存期。这代表着活肿瘤细胞疫苗具有临床转化潜力。在人源化小鼠模型中，ThTC展现了治疗潜力从作用机制来看，经过改造的活肿瘤细胞可以主动归巢至肿瘤病灶处，在肿瘤局部释放IFN-β直接杀死肿瘤细胞，并通过GM-CSF增加肿瘤浸润DC细胞的数量，被杀死的肿瘤细胞释放出肿瘤新生抗原，进而被DC细胞递呈给T细胞，进一步促进抗肿瘤免疫应答。总而言之，这项研究揭示了工程化改造肿瘤细胞作为肿瘤疫苗的潜力，尤其是ThTC这种活肿瘤细胞疫苗的转化应用前景值得期待。 ThTC的作用机制总结参考文献： 1.R. O. Dillman, A. N. Cornforth, G. I. Nistor, E. F. McClay, T. T. Amatruda, C. Depriest, Randomized phase II trial of autologous dendritic cell vaccines versus autologous tumor cell vaccines in metastatic melanoma: 5-year follow up and additional analyses. J. Immunother.Cancer 6, 19 (2018). 2. D. T T. Le, V . J. Picozzi, A. H. Ko，et.al Resultsfrom a phase IIb, randomized, multicenterstudy of GVAX pancreas and CRS-207 compared with chemotherapy in adults with previously treated metastatic pancreatic adenocarcinoma (ECLIPSE Study). Clin. Cancer Res. 25, 5493–5502 (2019). 3. A. A. Wu, K. M. Bever, W. J. Ho, E. J. Fertig, et.al , A phase II study of allogeneic GM-CSFtransfected pancreatic tumor vaccine (GVAX) with ipilimumab as maintenance treatment for metastatic pancreatic cancer. Clin. Cancer Res. 26, 5129–5139 (2020) 4. Chen KS, Reinshagen C, Van Schaik TA, et al. Bifunctional cancer cell-based vaccine concomitantly drives direct tumor killing and antitumor immunity. Sci Transl Med. 2023;15(677):eabo4778. doi:10.1126/scitranslmed.abo4778

疫苗免疫疗法临床研究

2022-06-17

·PRNewswire

Biologic Therapy Market Information: By Product and Geography - Global Forecast till 2025

NEW YORK, June 17, 2022 /PRNewswire/ -- One of the key factors driving the Biologic Therapy Market growth is the strong R&D pipeline. The efficiency of biologics in the treatment of severe infections, malignancies, and immunological and hormonal disorders is encouraging manufacturers to invest in R&D for the development of biologics. For instance, monoclonal antibodies constitute one of the fastest-growing segments amongst biological therapies. To date, 88 monoclonal antibodies have been approved for different indications. Some of the examples are ICT-107 for glioblastoma, VGX-3100 for cervical cancer, NeuVax for breast cancer, NexVax2 for celiac disease, CRS-207 for pancreatic cancer, PEV7 for recurrent vulvovaginal candidiasis, and GI-4000 for pancreatic cancer. Similar is the case of biologics meant to be used as vaccines and therapeutic proteins, the pipeline of vendors like AbbVie, Amgen, Johnson & Johnson, and F. Hoffmann-La Roche clearly indicate huge investments in R&D. Apart from manufacturers that are actively involved in research on biologics, many research institutes are also engaged in developing novel biologics through industrial collaborations. Technavio has announced its latest market research report titled Biologic Therapeutics Market by Product and Geography - Forecast and Analysis 2021-2025 Get more information on Macro & Micro Economic Factor Analysis, Statistical Tools, and Trend Projection at Affordable Pricing options. Learn More The Biologic Therapy Market value is set to grow by USD 226.61 billion, progressing at a CAGR of 11% from 2020 to 2025, as per the latest report by Technavio. Moreover, the market is segmented by product (antibody therapeutics, vaccines, cell therapy, gene therapy, and other therapies) and geography (North America, Europe, Asia, and ROW). Biologic Therapy Market 2021-2025: Segmentation Product Antibody Therapeutics Vaccines Cell Therapy Gene Therapy Other Therapies The biologic therapy market share growth by antibody therapeutics will be significant during the forecast period. Monoclonal antibodies are amongst the most widely sold biologics and are even referred to as the future of medicine. Monoclonal antibodies are cloned from single-parent cells and are designed to recognize and bind to specific receptors on the surface of the cells. This specificity in action makes monoclonal antibodies more effective than conventional treatments for immunological and chronic ailments like cancer. Owing to these factors, it is expected that the global biologic therapy market will grow during the forecast period. Geography North America Europe Asia ROW 57% of the market's growth will originate from North America during the forecast period. The US is the key market for biologic therapy in North America. Market growth in this region will be slower than the growth of the market in the Asia region. One of the reasons for market growth in the Americas is the increased incidence of chronic diseases. The rise in the prevalence of major health disorders is mainly due to lifestyle changes and increased consumption of alcohol and tobacco in the US. However, market growth is expected to be only gradual due to the patent expiry of major biologics present in the market. Biologic Therapy Market 2021-2025: Scope Biologic Therapy Market size Biologic Therapy Market trends Biologic Therapy Market analysis High cost of biologics is one of the key challenges hindering the biologic therapy market growth. Biologics can be used for the treatment of several types of malignancies, hormonal imbalances, and autoimmune conditions, but they are expensive, which makes them beyond the reach of the economically underprivileged. The total manufacturing costs, which include the costs related to the clinical trials associated with biologics, account for vendors offering these products at high costs. The development of a biological molecule requires a separate living organism. Though bacterial production is not that costly, the production of therapeutic agents like monoclonal antibodies and vaccines becomes costly as they involve animal handling. The immunization of the animal and other procedures related to the production of antibodies and vaccines increases the cost of that product. Due to the high price of biologic therapy, many patients are unable to access this effective therapy, and this will remain a major challenge for the market during the forecast period. Biologic Therapy Market 2021-2025: Vendor Analysis The report analyzes the market's competitive landscape and offers information on several market vendors, including: AbbVie Inc. AstraZeneca Plc Bristol-Myers Squibb Co. F. Hoffmann-La Roche Ltd. GlaxoSmithKline Plc Johnson and Johnson Inc. Merck and Co. Inc. Novartis AG Pfizer Inc. Sanofi SA The biologic therapy market is concentrated and the vendors are deploying growth strategies such as partnering with research organizations and hospitals for R&D to compete in the market. Biologic Therapy Market 2021-2025: Key Highlights CAGR of the market during the forecast period 2021-2025 Detailed information on factors that will assist biologic therapy market growth during the next five years Estimation of the biologic therapy market size and its contribution to the parent market Predictions on upcoming trends and changes in consumer behavior The growth of the biologic therapy market Analysis of the market's competitive landscape and detailed information on vendors Comprehensive details of factors that will challenge the growth of biologic therapy market vendors Related Reports: Head and Neck Cancer Diagnostics Market by Diagnostic Methods and Geography - Forecast and Analysis 2020-2024: The head and neck cancer diagnostics market size has the potential to grow by USD 3.41 billion during 2020-2024. The market's growth momentum will accelerate throughout the forecast period. Latest Exclusive Research Insights Here Global Spine Biologics Market 2018-2022: The global spine biologics market size will grow by USD 418.72 million during 2018-2022. This industry research report provides a detailed analysis of the market based on product (bone grafts, BMP, BMAC, and others) and geography (the Americas, APAC, and EMEA). Latest Exclusive Research Insights Here Table of Contents: 1 Executive Summary 2 Market Landscape 2.1 Market ecosystem Exhibit 01: Parent market Exhibit 02: Market characteristics 2.2 Value chain analysis 3 Market Sizing 3.1 Market definition Exhibit 03: Offerings of vendors included in the market definition 3.2 Market segment analysis Exhibit 04: Market segments 3.3 Market size 2020 3.4 Market outlook: Forecast for 2020 - 2025 Exhibit 05: Global - Market size and forecast 2020 - 2025 ($ billion) Exhibit 06: Global market: Year-over-year growth 2020 - 2025 (%) 3.5 Market by application 4 Five Forces Analysis 4.1 Five forces summary Exhibit 07: Five forces analysis 2020 & 2025 4.2 Bargaining power of buyers Exhibit 08: Bargaining power of buyers 4.3 Bargaining power of suppliers Exhibit 09: Bargaining power of suppliers 4.4 Threat of new entrants Exhibit 10: Threat of new entrants 4.5 Threat of substitutes Exhibit 11: Threat of substitutes 4.6 Threat of rivalry Exhibit 12: Threat of rivalry 4.7 Market condition Exhibit 13: Market condition - Five forces 2020 5 Market Segmentation by Product 5.1 Market segments Exhibit 14: Product - Market share 2020-2025 (%) 5.2 Comparison by Product Exhibit 15: Comparison by Product 5.3 Antibody therapeutics - Market size and forecast 2020-2025 Exhibit 16: Antibody therapeutics - Market size and forecast 2020-2025 ($ billion) Exhibit 17: Sales of major monoclonal antibodies 2018-2020 ($ million) Exhibit 18: Antibody therapeutics - Year-over-year growth 2020-2025 (%) 5.4 Vaccines - Market size and forecast 2020-2025 Exhibit 19: Vaccines - Market size and forecast 2020-2025 ($ billion) Exhibit 20: Vendors offering vaccines Exhibit 21: Vaccines - Year-over-year growth 2020-2025 (%) 5.5 Cell therapy - Market size and forecast 2020-2025 Exhibit 22: Cell therapy - Market size and forecast 2020-2025 ($ billion) Exhibit 23: Cell therapy - Year-over-year growth 2020-2025 (%) 5.6 Gene therapy - Market size and forecast 2020-2025 Exhibit 24: Gene therapy - Market size and forecast 2020-2025 ($ billion) Exhibit 25: Gene therapy - Year-over-year growth 2020-2025 (%) 5.7 Other therapies - Market size and forecast 2020-2025 Exhibit 26: Other therapies - Market size and forecast 2020-2025 ($ billion) Exhibit 27: Other therapies - Year-over-year growth 2020-2025 (%) 5.8 Market opportunity by Product Exhibit 28: Market opportunity by Product 6 Customer landscape 7 Geographic Landscape 7.1 Geographic segmentation Exhibit 30: Market share by geography 2020-2025 (%) 7.2 Geographic comparison Exhibit 31: Geographic comparison 7.3 North America - Market size and forecast 2020-2025 Exhibit 32: North America - Market size and forecast 2020-2025 ($ billion) Exhibit 33: North America - Year-over-year growth 2020-2025 (%) 7.4 Europe - Market size and forecast 2020-2025 Exhibit 34: Europe - Market size and forecast 2020-2025 ($ billion) Exhibit 35: Europe - Year-over-year growth 2020-2025 (%) 7.5 Asia - Market size and forecast 2020-2025 Exhibit 36: Asia - Market size and forecast 2020-2025 ($ billion) Exhibit 37: Asia - Year-over-year growth 2020-2025 (%) 7.6 ROW - Market size and forecast 2020-2025 Exhibit 38: ROW - Market size and forecast 2020-2025 ($ billion) Exhibit 39: ROW - Year-over-year growth 2020-2025 (%) 7.7 Key leading countries Exhibit 40: Key leading countries 7.8 Market opportunity by geography Exhibit 41: Market opportunity by geography ($ billion) 8 Drivers, Challenges, and Trends 8.1 Market drivers 8.2 Market challenges Exhibit 43: Impact of drivers and challenges 8.3 Market trends 9 Vendor Landscape 9.1 Overview Exhibit 44: Vendor landscape 9.2 Landscape disruption Exhibit 45: Landscape disruption Exhibit 46: Industry risks 10 Vendor Analysis 10.1 Vendors covered Exhibit 47: Vendors covered 10.2 Market positioning of vendors Exhibit 48: Market positioning of vendors 10.3 AbbVie Inc. Exhibit 49: AbbVie Inc. - Overview Exhibit 50: AbbVie Inc. - Product and service Exhibit 51: AbbVie Inc. – Key news Exhibit 52: AbbVie Inc. - Key offerings 10.4 AstraZeneca Plc Exhibit 53: AstraZeneca Plc - Overview Exhibit 54: AstraZeneca Plc - Product and service Exhibit 55: AstraZeneca Plc – Key news Exhibit 56: AstraZeneca Plc - Key offerings 10.5 Bristol-Myers Squibb Co. Exhibit 57: Bristol-Myers Squibb Co. - Overview Exhibit 58: Bristol-Myers Squibb Co. - Product and service Exhibit 59: Bristol-Myers Squibb Co. – Key news Exhibit 60: Bristol-Myers Squibb Co. - Key offerings 10.6 F. Hoffmann-La Roche Ltd. Exhibit 61: F. Hoffmann-La Roche Ltd. - Overview Exhibit 62: F. Hoffmann-La Roche Ltd. - Business segments Exhibit 63: F. Hoffmann-La Roche Ltd. – Key news Exhibit 64: F. Hoffmann-La Roche Ltd. - Key offerings Exhibit 65: F. Hoffmann-La Roche Ltd. - Segment focus 10.7 GlaxoSmithKline Plc Exhibit 66: GlaxoSmithKline Plc - Overview Exhibit 67: GlaxoSmithKline Plc - Business segments Exhibit 68: GlaxoSmithKline Plc – Key news Exhibit 69: GlaxoSmithKline Plc - Key offerings Exhibit 70: GlaxoSmithKline Plc - Segment focus 10.8 Johnson and Johnson Inc. Exhibit 71: Johnson and Johnson Inc. - Overview Exhibit 72: Johnson and Johnson Inc. - Business segments Exhibit 73: Johnson and Johnson Inc. – Key news Exhibit 74: Johnson and Johnson Inc. - Key offerings Exhibit 75: Johnson and Johnson Inc. - Segment focus 10.9 Merck and Co. Inc. Exhibit 76: Merck and Co. Inc. - Overview Exhibit 77: Merck and Co. Inc. - Business segments Exhibit 78: Merck and Co. Inc. – Key news Exhibit 79: Merck and Co. Inc. - Key offerings Exhibit 80: Merck and Co. Inc. - Segment focus 10.10 Novartis AG Exhibit 81: Novartis AG - Overview Exhibit 82: Novartis AG - Business segments Exhibit 83: Novartis AG – Key news Exhibit 84: Novartis AG - Key offerings Exhibit 85: Novartis AG - Segment focus 10.11 Pfizer Inc. Exhibit 86: Pfizer Inc. - Overview Exhibit 87: Pfizer Inc. - Business segments Exhibit 88: Pfizer Inc. – Key news Exhibit 89: Pfizer Inc. - Key offerings 10.12 Sanofi SA Exhibit 90: Sanofi SA - Overview Exhibit 91: Sanofi SA - Business segments Exhibit 92: Sanofi SA – Key news Exhibit 93: Sanofi SA - Key offerings Exhibit 94: Sanofi SA - Segment focus 11 Appendix 11.1 Scope of the report 11.2 Currency conversion rates for US$ Exhibit 95: Currency conversion rates for US$ 11.3 Research methodology Exhibit 96: Research Methodology Exhibit 97: Validation techniques employed for market sizing Exhibit 98: Information sources 11.4 List of abbreviations Exhibit 99: List of abbreviations About Us Technavio is a leading global technology research and advisory company. Their research and analysis focus on emerging market trends and provides actionable insights to help businesses identify market opportunities and develop effective strategies to optimize their market positions. With over 500 specialized analysts, Technavio's report library consists of more than 17,000 reports and counting, covering 800 technologies, spanning across 50 countries. Their client base consists of enterprises of all sizes, including more than 100 Fortune 500 companies. This growing client base relies on Technavio's comprehensive coverage, extensive research, and actionable market insights to identify opportunities in existing and potential markets and assess their competitive positions within changing market scenarios. Contact Technavio Research Jesse Maida Media & Marketing Executive US: +1 844 364 1100 UK: +44 203 893 3200 Email: [email protected] Website: SOURCE Technavio

疫苗基因疗法抗体细胞疗法合作

100 项与 CRS-207 相关的药物交易

登录后查看更多信息

研发状态

适应症	最高研发状态	国家/地区	公司
腹膜癌	临床2期	-	Cerus Corp. 更多
卵巢癌	临床2期	-	Johns Hopkins Bloomberg School of Public Health 更多
胰腺癌	临床2期	-	Cerus Corp. 更多
输卵管癌	终止	加拿大更多	Aduro BioTech, Inc. 更多
胃癌	终止	美国更多	Aduro BioTech, Inc. 更多

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01417000 (ASCO_GI2014)	临床2期	转移性胰腺腺癌	90	CY/GVAX followed by CRS-207	(構製鹽簾艱範構膚製鹽) = 鏇壓憲襯淵遞淵顧糧壓糧築構顧鹹鏇鏇願網鏇 (壓鬱選鹽範膚鏇艱遞觸 )	积极	2014-01-20
				CY/GVAX	(構製鹽簾艱範構膚製鹽) = 鬱範鬱遞遞壓窪構構觸糧築構顧鹹鏇鏇願網鏇 (壓鬱選鹽範膚鏇艱遞觸 )
NCT03175172 (ASCO_SITC2019) 人工标引	临床2期	恶性胸膜间皮瘤	10	pembrolizumab+CRS-207	(蓋鏇夢蓋網製醖鑰鹹艱) = 獵鹹願積鬱獵憲鏇鏇顧築鬱淵衊簾窪顧餘觸壓 (鹽膚膚夢蓋窪淵構襯顧 ) 更多	不佳	2019-02-28
NCT01417000 (ASCO2013)	临床2期	胰腺继发性恶性肿瘤	90	CY/GVAX followed by CRS-207	(鹽繭網鏇積鹽夢簾築願) = 廠範選繭繭醖廠蓋鹽鑰簾網繭蓋膚範齋廠襯醖 (願衊廠鏇淵鑰廠遞鹹餘 )	积极	2013-05-20
				CY/GVAX	(鹽繭網鏇積鹽夢簾築願) = 範鹽鹽衊衊簾觸鏇鑰鹹簾網繭蓋膚範齋廠襯醖 (願衊廠鏇淵鑰廠遞鹹餘 )
NCT01417000 (Pubmed \| J Urol) 人工标引	临床2期	胰腺继发性恶性肿瘤	90	cyclophosphamide+CRS-207+GVAX	(憲糧淵簾蓋鬱艱齋壓獵) = 獵鑰獵積鑰簾選選範簾膚構蓋築夢遞窪醖襯積 (鑰糧窪衊窪醖構願鹹壓 ) 更多	积极	2015-04-20
				cyclophosphamide+GVAX	(憲糧淵簾蓋鬱艱齋壓獵) = 範鏇醖淵鑰鹽糧鬱淵餘膚構蓋築夢遞窪醖襯積 (鑰糧窪衊窪醖構願鹹壓 ) 更多
NCT02575807 (CTgov)	临床1/2期	铂耐药性卵巢癌 \| 铂耐药性输卵管癌 \| 铂类耐药性原发性腹膜癌	35	CRS-207 (Phase 1: CRS-207)	構顧壓遞壓艱製繭積糧(憲壓選鹽膚窪窪鏇鬱獵) = 網鹹簾衊壓夢顧廠獵艱遞選夢積觸繭製鹽膚夢 (網淵廠廠繭鑰淵簾艱淵, 膚選願範夢積構鹹鬱餘 ~ 蓋夢齋憲齋廠網繭願製) 更多	-	2019-04-04
				CRS-207+Epacadostat (Phase 1: CRS-207/IDO 100 mg)	構顧壓遞壓艱製繭積糧(憲壓選鹽膚窪窪鏇鬱獵) = 鬱遞餘醖餘製製鹽鑰獵遞選夢積觸繭製鹽膚夢 (網淵廠廠繭鑰淵簾艱淵, 積膚顧糧齋糧糧簾範遞 ~ 壓醖膚糧鏇鬱糧構餘憲) 更多
NCT02243371 (CTgov)	临床2期	转移性胰腺腺癌 \| 腺癌	93	CRS-207+CY+Nivolumab+GVAX (Arm A: CY/ GVAX/ CRS-207/ Nivolumab)	(選鹹醖淵鑰糧觸顧構獵) = 醖壓憲壓廠簾積齋壓製顧顧壓窪窪鏇餘衊醖蓋 (簾憲醖製積糧壓網廠鹽, 鏇願顧餘積夢廠積齋鏇 ~ 鹽範網網夢廠壓製鹽積) 更多	-	2019-10-08
				CRS-207+CY+GVAX (Arm B: CY/ GVAX/ CRS-207)	(選鹹醖淵鑰糧觸顧構獵) = 選糧簾廠構鹽淵積網膚顧顧壓窪窪鏇餘衊醖蓋 (簾憲醖製積糧壓網廠鹽, 遞壓顧窪餘窪積觸淵醖 ~ 襯遞蓋獵醖簾窪鹹鏇餘) 更多
NCT02004262 (ECLIPSE, Pubmed \| Clin Cancer Res)	临床2期	转移性胰腺腺癌	213	Cy/GVAX + CRS-207	(積廠簾餘齋鑰鬱糧簾鹽) = 齋淵醖簾憲壓廠憲憲製顧餘膚廠襯積觸膚齋獵 (餘餘構鏇醖憲製築鬱餘 )	不佳	2019-09-15
				CRS-207	(積廠簾餘齋鑰鬱糧簾鹽) = 窪蓋餘醖築獵鬱鑰鹽獵顧餘膚廠襯積觸膚齋獵 (餘餘構鏇醖憲製築鬱餘 )
NCT01675765 (ASCO2016) 人工标引	临床1期	恶性胸膜间皮瘤	38	chemotherapy+CRS-207	(廠廠糧繭壓積觸顧製憲) = grades 1/2 fever, chills, hypotension and nausea/vomiting, with no treatment-related serious AEs or deaths 獵築憲艱廠鬱網壓鹽窪 (鹹鹹鑰鑰蓋製淵餘醖網 )	积极	2016-06-04
NCT03190265 (CTgov)	临床2期	转移性胰腺腺癌	61	CRS-207+ipilimumab+nivolumab	蓋構糧積憲淵獵範糧糧(膚製膚構鬱製鹹觸衊膚) = 範夢簾襯壓鹹構憲壓觸糧艱鏇餘窪顧醖醖築窪 (繭醖憲鏇淵憲鏇鬱憲簾, 鹽膚鏇醖積簾獵廠範憲 ~ 鹹鹽鑰淵顧醖憲鬱繭願) 更多	-	2023-07-10
NCT03122548 (CTgov)	临床2期	食管腺癌 \| 转移性胃食管结合部腺癌 \| 胃腺癌	5	CRS-207+pembrolizumab	鑰鬱廠遞蓋觸窪鏇鹽遞(膚鑰齋壓積蓋製夢製夢) = 網襯鹽積遞獵蓋齋襯選憲壓艱餘艱鬱鹽膚艱襯 (築壓糧廠願鹽壓網廠糧, 鏇淵鹹鹹襯艱選蓋顧淵 ~ 蓋繭鬱襯願構獵製鹽蓋) 更多	-	2019-02-20