Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Viral vectors encoding cancer/testis antigens for use in a method of prevention or treatment of cancer

A technology of cancer antigen and carrier, which is applied in the direction of virus/phage, tumor rejection antigen precursor, and the introduction of foreign genetic material by carrier, which can solve the problems of reducing the risk of amplification and strong immunogenicity

Pending Publication Date: 2021-05-11
LUDWIG INST FOR CANCER RES LTD
View PDF16 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Thus, MVA lacks the ability to mature virions in many mammalian cells and is associated with strong immunogenicity and reduced risk of expansion

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Viral vectors encoding cancer/testis antigens for use in a method of prevention or treatment of cancer
  • Viral vectors encoding cancer/testis antigens for use in a method of prevention or treatment of cancer
  • Viral vectors encoding cancer/testis antigens for use in a method of prevention or treatment of cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0184] Example 1: Induction of CD8 T cells against P1A by immunization with ChAdOx / MVA

[0185] P1A is a murine MAGE-type antigen that can be used to confirm the induction of CD8 responses against non-mutated MAGE-type antigens in syngeneic hosts and to induce protection against P1A-expressing tumors P815. It is a replacement for MAGE-A3 and NY-ESO-1.

[0186] Figure 1B A schematic diagram of the prime-boost immunization of mice from which peripheral blood mononuclear cells (PBMC) were obtained and tested for vaccination response is shown. figure 2CD8 in mice vaccinated with ChAdOx1 / MVA viral vector encoding P1A is shown + T cell response. Timeline according to vaccination protocol (Figure 1) – BL / 6, DBA / 2 and CD1 mice were vaccinated with ChAdOx1.P1A or ChAdOx1.P1A-Ii (prime) followed by MVA.P1A (boost) 4 weeks later ). To test P1A-specific T cell responses, PMBCs were stimulated ex vivo with the P1A peptide pool and the percentage of cells producing type I cytokine...

Embodiment 2

[0188] Example 2: Evaluation of the protective efficacy of P1A-carrying ChAdOx1 and MVA viral vectors against tumor formation

[0189] As part of assessing the protective efficacy of the vaccine against tumor challenge, mice were injected subcutaneously with tumor cells in serum-free cell culture medium on one side. After the appearance of overt tumors, their growth was recorded and mice were euthanized once the tumor size reached 10 mm in either direction. Tumor volume was measured using the formula: length (mm) x width2 (mm) x 0.5. Survival curves were drawn according to the Kaplan-Meier method, and differences in survival were tested using the log-rank test. P values ​​below 0.05 were considered significant.

[0190] In more detail, DBA / 2 mice were immunized with PBS, live L1210.P1A.B7-1 cells or given ChAdOx1-P1A(±Ii) / MVA-P1A prime-boost immunization at intervals of 4 weeks, and then on one side with 1.5x10 6 P815 cells or 1x10 6 15V4T3 cells were challenged by subc...

Embodiment 3

[0194] Example 3: Evaluation of Vaccine Therapeutic Efficacy of ChAdOx1 and MVA Viral Vectors Carrying P1A

[0195] Experiments are conducted to assess the therapeutic efficacy of vaccines. After the establishment of 15V4T3 tumors, mice were primed with ChAdOx vector from 5 days later, and then boosted with MVA vector on day 26. Vaccination regimens such as Figure 7 shown. Three different vaccination regimens were tested. Subcutaneously via the ventral side with 1x10 6 DBA / 2 mice were challenged with 15V4T3 cells, and then received 5 days after challenge: a single standard dose of ChAdOx-P1A (10 8 IU) / MVA-P1A (10 7 PFU) prime-boost vaccination, a single low-dose prime-boost vaccination (ChAdOx–10 7 IU, MVA–10 6 PFU), weekly alternating low-dose ChAdOx-P1A / MVA-P1A vaccination or weekly ChAdOx / MVA vaccination encoding the control antigen DPY. Growth and survival of 15V4T3 tumors in each treatment group were then monitored.

[0196] As shown in Figure 8, tumor growth ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

Chimpanzee adenovirus (ChAd) and MVA virus vectors containing polynucleotide sequences encoding cancer antigens are administered sequentially to a subject in a suitable adjuvant in order to achieve a prime boost effect. The polynucleotides are expressed in situ following administration to provide a MAGEA3 / linker / NY-ESO-1 fusion protein and variants thereof. Also, a hli / MAGEA3 / linker / NY-ESO-1 fusion protein and variants thereof. An improved T cell response is found. In a particular synergistic therapeutic approach a triple combination of ChAdOx and MVA vectors together with chemotherapeutic agent and checkpoint inhibitor results in depleted myeloid derived suppressor cells (MDSC) and dramatically improves survival time in a mouse model of cancer.

Description

technical field [0001] The present invention relates to viral vector-based vaccines for the prevention or treatment of cancer, and more particularly, to replication-defective adenovirus (Ad) and modified vaccinia virus Ankara (MVA) vectors containing cancer vaccine antigens of interest and for use in breastfeeding animal. Accordingly, the present invention relates to viral particles, immunogenic compositions comprising said viral particles and host cells comprising said viral vectors. The viral vector vaccine is used to treat a subject with cancer or prevent a subject from developing cancer. In a preferred protocol, the invention involves an initial administration with an Ad vector followed by a boost administration with an MVA vector. The present invention further provides vaccine compositions comprising the novel replication-deficient adenoviral vectors of the present invention. Background technique [0002] More than 1.6 million Americans are diagnosed with cancer each...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/00A61K39/395A61P35/00C12N15/861C12N15/863C07K16/28
CPCC12N2710/10343C12N2710/24143A61K39/001186A61K39/001188C07K14/4748C07K2319/02C07K2319/03A61P35/00A61K39/3955A61K2039/505A61K2039/545C07K16/2818A61K39/00118A61K2039/605A61K2300/00C12N15/86C12N15/62C07K16/2827A61K2039/585C07K14/70539C12N2710/10043C12N2710/24043
Inventor 伯努瓦·J·范登恩德卡罗尔·S·梁艾德里安·S·希尔伊琳娜·雷德琴科
Owner LUDWIG INST FOR CANCER RES LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com