The purpose of this study is to evaluate the clinical efficacy of an investigational agent, P10s-PADRE, a peptide mimotope-based vaccine in subjects with metastatic cancer.

开始日期2021-03-01

申办/合作机构

The University of Arkansas

NCT02938442 / Completed临床1/2期IIT

A Combined Phase i/II Efficacy Study of a Carbohydrate Mimotope-based Vaccine With MONTANIDE™ ISA 51 VG STERILE Combined With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer

The purpose of this study is to evaluate a new investigational cancer vaccine, P10s-PADRE in combination with standard neoadjuvant chemotherapy and surgery in patients with clinical stage I, II or III triple negative breast cancer (TNBC). This study will compare the vaccine plus standard neoadjuvant chemotherapy and surgery to standard neoadjuvant chemotherapy and surgery alone.

开始日期2019-01-25

申办/合作机构

University of Arkansas System

NCT02264236 / Withdrawn临床1/2期IIT

"Vaccination of Advanced-Stage Lung Cancer Patients" A Phase I/II Study of a Carbohydrate Mimotope Based Vaccine With MONTANIDETM ISA 51 VG ST Adjuvant

The overarching purpose of this study is to evaluate the clinical efficacy of an investigational agent, P10s-PADRE, a peptide mimotope-based vaccine, in combination with standard-of-care (SoC) treatment in subjects with advanced-stage (i.e., metastatic) Lung Cancer. Vaccine will consist of P10s-PADRE admixed with an adjuvant, MONTANIDETM ISA 51 VG. Up to one hundred fifty (150) subjects with advanced-stage Lung Cancer of any histologic type will be enrolled for this vaccine trial.
This single-arm, multi-site trial is designed to evaluate the therapeutic benefits of the vaccine in subjects with advanced-stage lung cancer. The primary objectives of the study are: (1) to monitor the safety and tolerability of the vaccine when it is administered in combination with SoC therapy; and (2) to determine whether immunization with vaccine can successfully elicit a robust immune response in subjects with advanced-stage lung cancer.

开始日期2015-10-01

申办/合作机构

The University of Arkansas

100 项与 P10s-PADRE vaccine(University of Arkansas) 相关的临床结果

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100 项与 P10s-PADRE vaccine(University of Arkansas) 相关的转化医学

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100 项与 P10s-PADRE vaccine(University of Arkansas) 相关的专利（医药）

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项与 P10s-PADRE vaccine(University of Arkansas) 相关的文献（医药）

2021-10-26·Oncotarget

P10s-PADRE vaccine combined with neoadjuvant chemotherapy in ER-positive breast cancer patients induces humoral and cellular immune responses

Article

作者: Abu-Rmaileh, Muhammad ; Post, Ginell R. ; Monzavi-Karbassi, Behjatolah ; Makhoul, Issam ; Siegel, Eric R. ; Beck, J. Thaddeus ; Jousheghany, Fariba ; Lee, John J. ; Kieber-Emmons, Thomas ; Pina-Oviedo, Sergio ; Ibrahim, Saddam Mohammed ; Rogers, Lora J.

Breast cancer patients diagnosed with HR+/HER2- tumors face a persistent risk of distant recurrence long after completion of their treatment. Strategies to induce anti-tumor immune responses could complement standard-of-care therapies for these patients. The current study was performed to examine the feasibility, safety and immunogenicity of adding P10s-PADRE to standard-of-care chemotherapy in HR+/HER2- early-stage breast cancer patients. Twenty-five subjects were treated in a single-arm Phase Ib clinical trial. Five different immunization schedules were considered to evaluate the feasibility of eliciting an immune response. The primary immunogenicity endpoint was antibody titer. The expression of several activation markers on natural killer (NK) cells and serum concentrations of Th1/Th2 cytokines were also examined. The percentage of tumor-infiltrating lymphocytes (TILs) was determined. Antibody response was superior in schedule C where 3 weekly immunizations preceded the first dose of chemotherapy. A significant change in CD16, NKp46 and CD94 expression levels on NK cells and a rise in serum content of IFN-γ was observed after treatment. Schedule C showed an increase in TILs in residual lesions. The combination therapy is safe and immunogenic with treatment schedule C being immunologically promising. Randomized trials focused on long-term survival outcomes are needed to evaluate clinical benefits.

2017-11-17·Oncotarget

Targeting tumor-associated carbohydrate antigens: a phase I study of a carbohydrate mimetic-peptide vaccine in stage IV breast cancer subjects

Article

作者: Pennisi, Angela ; Makhoul, Issam ; Emanuel, Peter D. ; Monzavi-Karbassi, Behjatolah ; Hutchins, Laura F. ; Pashov, Anastas D. ; Jousheghany, Fariba ; Siegel, Eric R. ; Guo, Xueyan ; Kieber-Emmons, Thomas

Tumor-associated carbohydrate antigens (TACAs) support cell survival that could be interrupted by anti-TACA antibodies. Among TACAs that mediate cell survival signals are the neolactoseries antigen Lewis Y (LeY) and the ganglioside GD2. To induce sustained immunity against both LeY and GD2, we developed a carbohydrate mimicking peptide (CMP) as a surrogate pan-immunogen that mimics both. This CMP, referred to as P10s, is the N-terminal half of a peptide vaccine named P10s-PADRE, the C-terminal half of which (PADRE) is a Pan-T-cell epitope. A Phase I dose-escalation trial of P10s-PADRE plus adjuvant MONTANIDE™ ISA 51 VG was conducted in subjects with metastatic breast cancer to test 300 and 500 μg/injection in two cohorts of 3 subjects each. Doses of the P10s-PADRE vaccine were administered to research participants subcutaneously on weeks 1, 2, 3, 7 and 19. Antibody responses to P10s, GD2, and LeY were measured by ELISA. The P10s-PADRE vaccine induced antibodies specifically reactive with P10s, LeY and GD2 in all 6 subjects. Serum antibodies displayed Caspase-3-dependent apoptotic functionality against LeY or GD2 expressing breast cancer cell lines. Immunization with the P10s-PADRE vaccine was well-tolerated and induced functional antibodies, and the data suggest potential clinical benefit.

2015-01-01·Human vaccines & immunotherapeutics3区 · 医学

Moving a Carbohydrate Mimetic Peptide into the clinic

3区 · 医学

Article

作者: Peter D Emanuel ; Behjatolah Monzavi-Karbassi ; Fariba Jousheghany ; Thomas Kieber-Emmons ; Laura Hutchins ; Issam Makhoul ; Eric Siegel ; Angela Pennisi

Tumor-Associated Carbohydrate Antigens (TACAs) are broad-spectrum targets for immunotherapy. Immunization with Carbohydrate Mimetic Peptides (CMPs) is a strategy to induce broad-spectrum TACA-reactive antibodies hypothesized to interfere with cellular pathways involved in tumor cell survival. A Phase I study was conducted with a first-in-man CMP referred to as P10s, conjugated to the Pan T cell carrier PADRE, along with MONTANIDE(™) ISA 51 VG as adjuvant over a course of 5 immunizations. While designed as a safety and tolerability study, the potential for therapeutic impact was observed in a subject with metastatic lesions as evaluated before and after vaccine treatment. The subject received Vinorelbine and Trastuzumab (VT) for two months prior to study eligibility. PET scans showed partial response in the lungs and complete resolution of a previously enlarged subpectoral lymph node. Immunization with P10s vaccine resulted in responses to P10s, with serum and plasma antibodies reactive with and cytotoxic to human breast cancer cells in vitro, including the Trastuzumab-resistant HCC1954 cell line. However, the patient developed cystic masses in the brain parenchyma with no apparent evidence of metastases. The subject was switched to Docetaxel, Pertuzumab and Trastuzumab a year later, and her last PET scan showed a complete response in the lungs and lymph nodes. Incubation of cancer cells with a combination of vaccine-induced serum and docetaxel suggests that the induced antibodies sensitize tumor cells for more efficient killing upon administration of docetaxel. The data suggest that P10s-PADRE induces anti-tumor antibody response that in combination with chemotherapy can affect metastatic lesions in breast cancer patients.

项与 P10s-PADRE vaccine(University of Arkansas) 相关的新闻（医药）

2023-08-07

·药研网

GUCY2C（GCC）：阻击结直肠癌

在2023 ASCO（美国临床肿瘤学会）年会上，由安徽省肿瘤医院生物治疗科牵头发起的CAR-T细胞治疗晚期结直肠癌临床研究结果显示，在所有肿瘤分期的结直肠癌中，鸟苷酸环化C（GUCY2C）的表达均超过90%，且靶向GUCY2C的CAR-T的细胞能够安全有效的清除结直肠癌细胞。该临床结果再一次把GUCY2C和结直肠癌（CRC）强势推入公众视野。此前我们介绍过一些结直肠癌靶点，如LY6G6D，GPA33，CDH17等，CRC是威胁我国居民生命健康的主要癌症之一，根据国家癌症中心2022年发布的报告，结直肠癌已成为仅次于肺癌的第二大发病癌种。而在2022年，斯丹赛的GUCY2C CAR-T产品GCC19CART获FDA授予快速通道资格，用于治疗复发难治性转移性结直肠癌，再次证明GUCY2C是治疗CRC的强有力靶点。GUCY2C即鸟苷酸环化酶 C，又称GC-C，或STa受体/STaR，是一种在肠上皮细胞上表达的跨膜受体，属于鸟苷酸环化酶家族。GUCY2C由GUCY2C基因编码，其蛋白结构由胞外结构域、跨膜区和胞内结构域三大部分组成，属于I型跨膜蛋白。GUCY2C结构（doi.org/10.1186/s40425-019-0576-2）当配体与GUCY2C结合后可催化GTP转化为cGMP，并启动下游cGMP相关信号通路。此外，GUCY2C-cGMP 信号轴可以维持正常的细胞内和细胞外离子浓度以及体液和电解质平衡，并维持正常肠道功能，而GUCY2C-cGMP信号轴的失调会促进结直肠癌的发展。GUCY2C-cGMP信号轴（doi.org/10.3389/fonc.2018.00299）吉满生物推出构建GUCY2C(GCC)过表达稳定细胞系/抗体的服务（详细数据见文末），充分满足药物研发需求，助力药物临床申报。目前国内进展最快的是上海斯丹赛生物研发的GCC19CART，处于临床I期，已获美国FDA快速通道资格，今年ASCO年会上公布了I期剂量扩展数据。截至2023年1月28日，该试验共纳入21名受试者，注输剂量为1x106（13人）或2x106 CAR T-cells/kg（8人）。两个剂量水平的总ORR为28.6%（6/21）。剂量水平1的ORR为15.4%（2/13），mPFS为1.9个月，mOS为13.3个月；剂量水平2 的 ORR 为 50%（4/8），mPFS为6.3个月，mOS为18.3个月。最常见的不良反应是CRS 21/21 例（1 级 19/21 例（90.48%）或 2 级 2/21 例（9.52%））和腹泻 21/21 例（1 级 6/21 例（28.57%）、2 级 5/21 例（23.81%）、3 级 9/21 例（42.86%）或 4 级 1/21 例（4.76%））。所有出现 3 级及以上副作用的患者都得到了很好的控制。2/21（9.52%）例患者出现3级或4级免疫效应细胞相关神经毒性综合征（ICANS），使用皮质类固醇后即可缓解。除了CAR-T赛道外，GUCY2C还被用于开发单抗、双抗和ADC药物。由辉瑞研发的PF-0706119是GUCY2C/CD3双抗，处于临床I期，临床前数据表明PF-0706119具有良好的抗肿瘤疗效，并且与anti-PD-1/PD-L1或者VEGF抑制剂联用，可以进一步提高治疗效果。 PF-07062119结构示意图（DOI：10.1158/1078-0432.CCR-19-3275）海德堡/华东医药开发了一款GUCY2C-ADC药物HDP-104，目前处于临床前，是通过海德堡ATAC技术平台开发，ATAC平台采用鹅膏毒素作为载荷。推荐阅读：Heidelberg第三代ADCs此外，美国Sidney Kimmel癌症中心还开发了相关疫苗，通过将GUCY2C分子与增强免疫反应的分子PADRE连接起来，并将其加载到腺病毒载体中，进而开发了专门针对结直肠癌的疫苗Ad5-GUCY2C-PADRE。临床前研究表明，该疫苗可激活CD8+T细胞产生免疫应答，预防结直肠癌转移，而在I期小型临床试验中，10名大肠癌患者接种了疫苗，并接受了6个月的随访。最终得到的结果是阳性，且没有出现严重的不良反应。GUCY2C作为肠道信号系统的重要成员，将GUCY2C-cGMP 轴作为结直肠癌预防及治疗目标在目前已具有一定理论基础。不管是CAR-T疗法还是抗体、ADC，都旨在为癌症治疗提供新的选择。新的免疫疗法的开展必将为胃肠道恶性肿瘤的治疗带来新的见解与机遇，期待GUCY2C相关治疗产品的百花齐放。用心做好细胞，为更好的靶向药吉满生物科技（上海）有限公司，是位于上海浦东的一家以创新为驱动的工程化细胞系研发公司，基于自有的国内最大报告基因平台、慢病毒平台以及最迅速的药研网资讯平台，目前已构建出500余株现货单克隆细胞系产品，覆盖ROR1/DLL3/SLC39A6/TROP2/BCMA/BDCA/TREM2……200余新药热门靶点，其中有90余靶点开发有对应luciferase reporter方法，更有国内独家/首家CCR8, BDCA, TREM2和GAPR等luciferase的assay平台。GUCY2C（GCC）细胞/抗体产品列表部分结果：H_GUCY2C HEK-293 Cell Line（Genomeditech/GM-C33482）使用Anti-H_GUCY2C hIgG1 Antibody(Indusatumab)（Genomeditech/GM-28860AB）流式验证结果H_GUCY2C CHO-K1 Cell Line（Genomeditech/GM-C19042）使用Anti-H_GUCY2C hIgG1 Antibody(Indusatumab)（Genomeditech/GM-28860AB）流式验证结果吉满生物助力药物研发，紧随前沿靶点资讯，储备几百株现货细胞，覆盖GPCR、细胞因子、免疫检查点、TAA等多领域近200余个靶点。2020年底成立专业细胞系子品牌DDXCELL，同时已建立了DDXCELL现货查询小程序。截止当前已布局近200个热门靶向药靶点500余株细胞系，旨在助力、加速大分子早期研发，做到进口细胞的国产替代。同时可根据客户需求提供细胞系服务。细胞系现货查询请扫码👇

ASCO会议临床1期细胞疗法快速通道临床结果

100 项与 P10s-PADRE vaccine(University of Arkansas) 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
肿瘤转移	临床2期	-	The University of Arkansas	2021-03-01
实体瘤	临床2期	-	The University of Arkansas	2021-03-01
三阴性乳腺癌	临床2期	美国	University of Arkansas System	2019-01-25
晚期肺腺癌	临床2期	美国	The University of Arkansas	2015-10-01
肺癌	临床2期	美国	The University of Arkansas	2015-10-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02938442 (CTgov)	临床1/2期	三阴性乳腺癌	16	P10s-PADRE+cyclophosphamide+Paclitaxel+Doxorubicin	構艱獵繭網衊艱齋鏇鬱(鹽鬱糧鹹膚衊夢壓願糧) = 夢鑰襯繭遞繭襯築鏇製鑰鏇窪鹹鹽窪膚獵糧顧 (餘衊願齋遞襯繭膚遞鑰, 製夢鬱膚壓獵鏇製願鑰 ~ 鏇範廠繭遞夢壓願觸獵) 更多	-	2024-07-05
NCT01390064 (CTgov)	临床1期	转移性乳腺癌	6	Mimotope P10s-PADRE/MONTANIDE ISA 51 VG (Initial Cohort)	艱選衊鹹鹽膚餘醖網獵(廠襯鬱夢簾淵餘艱窪製) = 襯鑰選鹹夢廠淵憲餘壓窪廠壓鹽憲夢願夢顧製 (鏇構鏇齋遞積願繭築衊, 觸選憲糧選齋繭鏇醖鏇 ~ 積艱窪鹽齋鑰壓窪遞醖) 更多	-	2019-06-03
NCT01390064 (CTgov)	临床1期	转移性乳腺癌	6	Mimotope P10s-PADRE/MONTANIDE ISA 51 VG (Escalation Cohort)	艱選衊鹹鹽膚餘醖網獵(廠襯鬱夢簾淵餘艱窪製) = 願艱夢築憲構餘選壓構窪廠壓鹽憲夢願夢顧製 (鏇構鏇齋遞積願繭築衊, 積醖範壓築範窪蓋遞鏇 ~ 鬱製廠築製顧廠願窪夢) 更多	-	2019-06-03