Delving into the Latest Updates on Neoantigen DNA vaccine (AstraZeneca/Washington University School of Medicine) with Synapse

Overview

Basic Info

Drug Type

Personalized antigen vaccine, Therapeutic vaccine

Synonyms-

Target-

Mechanism

Immunostimulants

Therapeutic Areas

NeoplasmsRespiratory Diseases

Active Indication

Extensive stage Small Cell Lung Cancer

Inactive Indication

Breast CancerMetastatic Renal Cell CarcinomaPancreatic Cancer+ [2]

Originator Organization

MedImmune LLC

Washington University School of Medicine

Active Organization

Washington University School of Medicine

AstraZeneca PLC

Inactive Organization

Bristol Myers Squibb Co.

MedImmune LLC

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

Login to view timeline

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.

Start Date31 Aug 2020

Sponsor / Collaborator

Washington University School of Medicine

[+1]

NCT03199040 / TerminatedPhase 1IIT

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.

Start Date23 Jul 2019

Sponsor / Collaborator

Washington University School of Medicine

[+3]

100 Clinical Results associated with Neoantigen DNA vaccine (AstraZeneca/Washington University School of Medicine)

Login to view more data

100 Translational Medicine associated with Neoantigen DNA vaccine (AstraZeneca/Washington University School of Medicine)

Login to view more data

100 Patents (Medical) associated with Neoantigen DNA vaccine (AstraZeneca/Washington University School of Medicine)

Login to view more data

4

Literatures (Medical) associated with Neoantigen DNA vaccine (AstraZeneca/Washington University School of Medicine)

01 Aug 2024·MedComm

Circular RNA‐based neoantigen vaccine for hepatocellular carcinoma immunotherapy

Article

Author: 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.

02 Nov 2019·OncoImmunologyQ2 · MEDICINE

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

Q2 · MEDICINE

ArticleOA

Author: 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

Author: 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 ; Chen, Michael Y. ; Miller, Christopher A ; Ma, Cynthia X ; Zhang, Felicia ; Hagemann, Ian S. ; Griffith, Obi ; Myers, Nancy B. ; Miller, Christopher A. ; Sankpal, Narendra V ; Singhal, Kartik ; Zhang, Xiuli ; Fleming, Timothy P. ; Schreiber, Robert D ; Schreiber, Robert D. ; Vickery, Tammi ; Li, Lijin ; Yu, Yik Yeung ; Hagemann, Ian S ; Chen, Ina ; Hansen, Ted H. ; 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 Deals associated with Neoantigen DNA vaccine (AstraZeneca/Washington University School of Medicine)

Login to view more data

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Breast Cancer	Phase 3	US	Washington University School of Medicine	-
Prostatic Cancer	Phase 3	US	Bristol Myers Squibb Co.	-
Prostatic Cancer	Phase 3	US	Washington University School of Medicine	-
Extensive stage Small Cell Lung Cancer	Phase 2	US	AstraZeneca PLC	30 Mar 2022
Extensive stage Small Cell Lung Cancer	Phase 2	US	Washington University School of Medicine	30 Mar 2022
Metastatic Renal Cell Carcinoma	Preclinical	-	Washington University School of Medicine	31 Aug 2020
Triple Negative Breast Cancer	Preclinical	US	MedImmune LLC	23 Jul 2019
Pancreatic Cancer	Preclinical	US	Washington University School of Medicine	05 Jan 2018

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03199040 (CTgov)	Phase 1	Triple Negative Breast Cancer	18	TDS-IM system (Inchor Medical Systems)+Durvalumab+Neoantigen DNA vaccine (Neoantigen DNA Vaccine + Durvalumab)	ygddchneyv(dqgexcuxhs) = srjmdbaipa xtthymgmyv (vmtvzaotvo, pezzlbelyd - mpwujuqdjm) View more	-	14 Dec 2023
NCT03199040 (CTgov)	Phase 1	Triple Negative Breast Cancer	18	TDS-IM system (Inchor Medical Systems)+Neoantigen DNA vaccine (Neoantigen DNA Vaccine)	ygddchneyv(dqgexcuxhs) = lfnkljbhvd xtthymgmyv (vmtvzaotvo, lqicpjqshr - fmaszcnggn) View more	-	14 Dec 2023
NCT03122106 (CTgov)	Phase 1	Pancreatic Cancer	15	Peripheral blood draws+Personalized neoantigen DNA vaccine	(xihwwkfmge) = wykwokbjbq rpzuyqdyhd (isgdbkgyfl, stmavhbten - dbzonuibaf) View more	-	04 Oct 2022