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Targeted neoepitope vectors and methods therefor

A new epitope and carrier technology, applied in the field of recombinant nucleic acid therapeutics, can solve the problems of prohibitive production time limit and poor effect, etc.

Active Publication Date: 2020-01-07
河谷细胞有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Depending on the type and rate of growth of the cancer, such production timelines can be prohibitive
In addition, immune stimulation with only virally expressed proteins is generally less effective and additional therapeutic modalities such as cytokines are often required to elicit the desired therapeutic effect
[0009] Thus, although a variety of methods are known in the art for identifying and delivering neo-epitopes to multiple cells, all or nearly all of these methods suffer from various disadvantages, particularly in terms of efficacy and time requirements

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  • Targeted neoepitope vectors and methods therefor
  • Targeted neoepitope vectors and methods therefor
  • Targeted neoepitope vectors and methods therefor

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[0132] Exemplary sequence alignment

[0133] Neo-epitope sequences were determined by in silico by position-guided simultaneous alignment of tumor and normal samples using BAM files and BAM servers, as disclosed eg in US 2012 / 0059670 and US 2012 / 0066001. Specifically, tumors for DNA analysis were from the B16-F10 mouse melanoma line, and matched normal controls were blood from C57b1 / 6 parental mouse DNA. These results were filtered for expression by RNA sequencing of the tumor cell line. The neo-epitopes found to be expressed were further analyzed for binding affinity towards murine MHC-I (here Kb) and MHC-II (here I-Ab). After an additional step of dbSNP filtering, selected binders (with affinities equal to or less than 200 nM) were further analyzed to generate representative A score for the likelihood of the presence and / or strength of a hydrophobic sequence or signal peptide is present. The best scoring alignment (lowest likelihood of hydrophobic sequence or signal pepti...

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Abstract

Systems and methods are presented that allow for selection of tumor neoepitopes that are then used to generate recombinant nucleic acids that encode one or more polytopes that are optimized for propertrafficking and processing. In preferred methods, the polytopes are encoded in a plasmid and / or a viral expression system for use as a therapeutic agent.

Description

[0001] This application claims priority to our co-pending U.S. Provisional Patent Application Serial No. 62 / 489,102 filed April 24, 2017. technical field [0002] The field of the invention is improved compositions and methods of neoepitope-based immunotherapeutics, and in particular the invention relates to recombinant nucleic acid therapeutics in the treatment of cancer. Background technique [0003] The Background Description includes information useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, nor is any publication specifically or implicitly referenced to be prior art. [0004] All publications and patent applications herein are incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. If a definition or usage of a term in an i...

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/70C12N15/81C07K14/47A61K39/00A61K39/12A61P35/00
CPCA61K39/0011A61K39/12A61P35/00C12N15/86C12N15/70C12N15/81A61K2039/51A61K2039/523A61K2039/5256A61K2039/53A61K2039/585C12N2710/10343C07K14/47C07K14/70596A61K2039/70C12N2710/10043A61K2039/6031Y02A50/30A61K39/001102A61K39/39C12N15/861C12N2799/022C12N2710/10011C12N2710/10021C07K14/4748C07K2319/06C12N2710/10041
Inventor 卡伊万·尼亚兹
Owner 河谷细胞有限公司