Neoantigen DNA vaccine (AstraZeneca/Washington University School of Medicine)(Neoantigen DNA vaccine (AstraZeneca/Washington University School of Medicine))

概要

基本信息

药物类型

个性化抗原疫苗、治疗性疫苗

别名-

靶点-

作用机制

免疫刺激剂

治疗领域

在研适应症

非在研适应症

原研机构

Washington University School of Medicine

在研机构

Washington University School of Medicine

AstraZeneca PLC

非在研机构

Bristol Myers Squibb Co.

MedImmune LLC

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

6

项与 Neoantigen DNA vaccine (AstraZeneca/Washington University School of Medicine) 相关的临床试验

NCT04397003

/ Recruiting临床2期IIT

Phase II Study of a Personalized Neoantigen Vaccine in Combination With Durvalumab (MEDI4736) in Extensive Stage Small Cell Lung Cancer

The investigators hypothesize that a personalized neoantigen vaccine combined with durvalumab will improve the progression free survival of patients with extensive state small cell lung cancer (ES-SCLC).

开始日期2022-03-30

申办/合作机构

Washington University School of Medicine

[+2]

NCT03598816

/ Withdrawn临床2期IIT

A Randomized Phase II PIVOT-RCC (PolyImmune {Durvalumab (MEDI4736) and Tremelimumab} & Vaccine Orchestrated Treatment for Patients With Advanced/Metastatic Renal Cell Carcinoma) Trial

Reported in the 2018 NEJM (378; 1277) article, the combination of checkpoint inhibitors ipilimumab (anti-CTLA-4 antibody) and nivolumab (anti-PD-1 antibody) phase III trial Checkmate 214 demonstrated statistically significant (P<0.0001) improvement of overall response rate (ORR) at 42% (95% confidence interval (CI), 37-47%) compared to standard of care (SOC) sunitinib at 27% (95% CI, 22-31%) in treatment naïve advanced or metastatic clear cell renal cell carcinoma (ccRCC). This study also showed increased survival benefit of Ipi+Nivo over sunitinib in the IMDC intermediate-poor risk ccRCC patients. Accordingly, the Ipi+Nivo was just approved by U.S. FDA in April 2018 for treating metastatic ccRCC. Hence, the investigators hypothesized that the combination of durvalumab and tremelimumab is similarly efficacious in advanced or metastatic RCC. Furthermore, the investigators also hypothesize that the administration of personalized neoantigen DNA vaccine will further enhance anti-tumor immune response in RCC.

开始日期2020-08-31

申办/合作机构

Washington University School of Medicine

[+1]

NCT03199040

/ Terminated临床1期IIT

A Randomized Phase 1 Trial of Neoantigen DNA Vaccine Alone vs. Neoantigen DNA Vaccine Plus Durvalumab in Triple Negative Breast Cancer Patients Following Standard of Care Therapy

This is a single institution, open-label randomized phase 1 trial of neoantigen DNA vaccine alone vs. neoantigen DNA vaccine plus durvalumab in triple negative breast cancer (TNBC) patients following standard of care therapy. Patients with newly diagnosed clinical stage II-III TNBC are eligible for enrollment. Patients will receive standard of care therapy including chemotherapy, surgery and radiation therapy as clinically indicated. Following standard of care therapy, patients will be randomized to receive either a neoantigen DNA vaccine alone, or a neoantigen DNA vaccine + durvalumab.

开始日期2019-07-23

申办/合作机构

Washington University School of Medicine

[+3]

100 项与 Neoantigen DNA vaccine (AstraZeneca/Washington University School of Medicine) 相关的临床结果

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100 项与 Neoantigen DNA vaccine (AstraZeneca/Washington University School of Medicine) 相关的转化医学

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100 项与 Neoantigen DNA vaccine (AstraZeneca/Washington University School of Medicine) 相关的专利（医药）

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4

项与 Neoantigen DNA vaccine (AstraZeneca/Washington University School of Medicine) 相关的文献（医药）

2024-08-01·MedComm

Circular RNA‐based neoantigen vaccine for hepatocellular carcinoma immunotherapy

Article

作者: Cai, Guang ; Cai, Zhixiong ; Li, Yingying ; Zhang, Cuilin ; Gao, Shaodong ; Zhao, Bixing ; Liu, Xiaolong ; Li, Fang ; Zhuang, Qiuyu ; Wang, Yingchao ; Wang, Fei

AbstractmRNA vaccines are regarded as a highly promising avenue for next‐generation cancer therapy. Nevertheless, the intricacy of production, inherent instability, and low expression persistence of linear mRNA significantly restrict their extensive utilization. Circular RNAs (circRNAs) offer a novel solution to these limitations due to their efficient protein expression ability, which can be rapidly generated in vitro without the need for extra modifications. Here, we present a novel neoantigen vaccine based on circRNA that induces a potent anti‐tumor immune response by expressing hepatocellular carcinoma‐specific tumor neoantigens. By cyclizing linearRNA molecules, we were able to enhance the stability of RNA vaccines and form highly stable circRNA molecules with the capacity for sustained protein expression. We confirmed that neoantigen‐encoded circRNA can promote dendritic cell (DC) activation and enhance DC‐induced T‐cell activation in vitro, thereby enhancing T‐cell killing of tumor cells. Encapsulating neoantigen‐encoded circRNA within lipid nanoparticles for in vivo expression has enabled the creation of a novel circRNA vaccine platform. This platform demonstrates superior tumor treatment and prevention in various murine tumor models, eliciting a robust T‐cell immune response. Our circRNA neoantigen vaccine offers new options and application prospects for neoantigen immunotherapy in solid tumors.

2019-11-02·OncoImmunology2区 · 医学

A poly-neoantigen DNA vaccine synergizes with PD-1 blockade to induce T cell-mediated tumor control

2区 · 医学

ArticleOA

作者: Arens, Ramon ; Han, Wanda ; Tondini, Elena ; Ossendorp, Ferry ; Camps, Marcel ; van Bergen, Jeroen ; van Duikeren, Suzanne ; Zondag, Gerben ; Arakelian, Tsolere ; Oosterhuis, Koen

The combination of immune-stimulating strategies has the potency to improve immunotherapy of cancer. Vaccination against neoepitopes derived from patient tumor material can generate tumor-specific T cell immunity, which could reinforce the efficacy of checkpoint inhibitor therapies such as anti-PD-1 treatment. DNA vaccination is a versatile platform that allows the inclusion of multiple neoantigen-coding sequences in a single formulation and therefore represents an ideal platform for neoantigen vaccination. We developed an anti-tumor vaccine based on a synthetic DNA vector designed to contain multiple cancer-specific epitopes in tandem. The DNA vector encoded a fusion gene consisting of three neoepitopes derived from the mouse colorectal tumor MC38 and their natural flanking sequences as 40 amino acid stretches. In addition, we incorporated as reporter epitopes the helper and CTL epitope sequences of ovalbumin. The poly-neoantigen DNA vaccine elicited T cell responses to all three neoantigens and induced functional CD8 and CD4 T cell responses to the reporter antigen ovalbumin after intradermal injection in mice. The DNA vaccine was effective in preventing outgrowth of B16 melanoma expressing ovalbumin in a prophylactic setting. Moreover, the combination of therapeutic DNA vaccination and anti-PD-1 treatment was synergistic in controlling MC38 tumor growth whereas individual treatments did not succeed. These data demonstrate the potential of DNA vaccination to target multiple neoepitopes in a single formulation and highlight the cooperation between vaccine-based and checkpoint blockade immunotherapies for the successful eradication of established tumors.

Genome Medicine

Neoantigen DNA vaccines are safe, feasible, and induce neoantigen-specific immune responses in triple-negative breast cancer patients

Article

作者: Sturmoski, Mark A ; Fleming, Timothy P ; Mardis, Elaine R ; Gao, Feng ; Mardis, Elaine R. ; Gillanders, William E ; Goedegebuure, S Peter ; Hansen, Ted H ; Foluso, Ademuyiwa ; Hundal, Jasreet ; Kim, Samuel W. ; Chen, Michael Y ; Griffith, Malachi ; Miller, Christopher A ; Chen, Michael Y. ; Ma, Cynthia X ; Zhang, Felicia ; Hagemann, Ian S. ; Griffith, Obi ; Myers, Nancy B. ; Miller, Christopher A. ; Sankpal, Narendra V ; Singhal, Kartik ; Fleming, Timothy P. ; Zhang, Xiuli ; Schreiber, Robert D ; Vickery, Tammi ; Li, Lijin ; Schreiber, Robert D. ; Yu, Yik Yeung ; Chen, Ina ; Hansen, Ted H. ; Hagemann, Ian S ; Gillanders, William E. ; Ma, Cynthia X. ; Suresh, Rama ; McLellan, Michael D. ; Davidson, Jesse T. ; McLellan, Michael D ; Davies, Sherri ; Davidson, Jesse T ; Goedegebuure, S. Peter ; Sankpal, Narendra V. ; Kim, Samuel W ; Mishra, Rashmi ; Sturmoski, Mark A. ; Wang-Gillam, Andrea ; Myers, Nancy B ; Myles, Stephanie

AbstractBackgroundNeoantigen vaccines can induce or enhance highly specific antitumor immune responses with minimal risk of autoimmunity. We have developed a neoantigen DNA vaccine platform capable of efficiently presenting both HLA class I and II epitopes and performed a phase 1 clinical trial in triple-negative breast cancer patients with persistent disease on surgical pathology following neoadjuvant chemotherapy, a patient population at high risk of disease recurrence.MethodsExpressed somatic mutations were identified by tumor/normal exome sequencing and tumor RNA sequencing. The pVACtools software suite of neoantigen prediction algorithms was used to identify and prioritize cancer neoantigens and facilitate vaccine design for manufacture in an academic GMP facility. Neoantigen DNA vaccines were administered via electroporation in the adjuvant setting (i.e., following surgical removal of the primary tumor and completion of standard of care therapy). Vaccines were monitored for safety and immune responses via ELISpot, intracellular cytokine production via flow cytometry, and TCR sequencing.ResultsEighteen subjects received three doses of a neoantigen DNA vaccine encoding on average 11 neoantigens per patient (range 4–20). The vaccinations were well tolerated with relatively few adverse events. Neoantigen-specific T cell responses were induced in 14/18 patients as measured by ELISpot and flow cytometry. At a median follow-up of 36 months, recurrence-free survival was 87.5% (95% CI: 72.7–100%) in the cohort of vaccinated patients.ConclusionOur study demonstrates neoantigen DNA vaccines are safe, feasible, and capable of inducing neoantigen-specific immune responses.Clinical trial registration numberNCT02348320.

100 项与 Neoantigen DNA vaccine (AstraZeneca/Washington University School of Medicine) 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
广泛期小细胞肺癌	临床2期	美国	AstraZeneca PLC	2022-03-30
广泛期小细胞肺癌	临床2期	美国	Washington University School of Medicine	2022-03-30
转移性肾细胞癌	临床2期	-	Washington University School of Medicine	2020-08-31
三阴性乳腺癌	临床2期	美国	MedImmune LLC	2019-07-23
胰腺癌	临床2期	美国	Washington University School of Medicine	2018-01-05
乳腺癌	药物发现	美国	Washington University School of Medicine	-
前列腺癌	药物发现	美国	Bristol Myers Squibb Co.	-
前列腺癌	药物发现	美国	Washington University School of Medicine	-

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临床结果

适应症

分期

评价

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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


NCT03199040 (CTgov)	临床1期	三阴性乳腺癌	18	TDS-IM system (Inchor Medical Systems)+Durvalumab+Neoantigen DNA vaccine (Neoantigen DNA Vaccine + Durvalumab)	鹹鹽遞鏇觸衊獵鬱艱蓋(網淵願鹹積壓積夢遞願) = 構窪積襯壓齋製糧齋繭選齋積夢壓顧構膚膚鹽 (窪壓蓋構蓋鑰襯廠顧齋, 選鏇觸製淵夢遞窪製衊 ~ 積築鹹觸積衊範積壓鑰) 更多	-	2023-12-14
NCT03199040 (CTgov)	临床1期	三阴性乳腺癌	18	TDS-IM system (Inchor Medical Systems)+Neoantigen DNA vaccine (Neoantigen DNA Vaccine)	鹹鹽遞鏇觸衊獵鬱艱蓋(網淵願鹹積壓積夢遞願) = 壓鹽壓鏇鏇構淵齋蓋餘選齋積夢壓顧構膚膚鹽 (窪壓蓋構蓋鑰襯廠顧齋, 廠餘淵膚範選艱顧壓壓 ~ 構齋淵淵網齋襯廠範衊) 更多	-	2023-12-14
NCT03122106 (CTgov)	临床1期	胰腺癌	15	Peripheral blood draws+Personalized neoantigen DNA vaccine	(衊簾艱鏇範鹽構壓鬱襯) = 壓夢選齋積餘衊鏇餘鬱淵鏇衊夢積範鹹衊構蓋 (鬱艱襯廠夢顧構膚簾醖, 壓遞構鬱憲遞蓋衊積獵 ~ 網窪鹹壓構製繭鑰獵築) 更多	-	2022-10-04