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Sequence arrangements and sequences for neoepitope presentation

A new epitope and sequence technology, applied in the field of immunotherapy compositions, can solve the problems of unpredictable treatment success and so on

Inactive Publication Date: 2019-04-02
河谷细胞有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Furthermore, especially when multiple peptides are expressed in antigen-presenting cells (e.g., dendritic cells), the processing of precursor proteins to generate neo-epitopes remains incompletely understood, thus leading to therapeutic the unpredictability of success

Method used

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  • Sequence arrangements and sequences for neoepitope presentation
  • Sequence arrangements and sequences for neoepitope presentation
  • Sequence arrangements and sequences for neoepitope presentation

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Embodiment

[0107] Exemplary sequence alignment

[0108] Neo-epitope sequences were determined via in silico by position-directed simultaneous alignment of tumor and normal samples, eg as disclosed in US2012 / 0059670 and US2012 / 0066001 using BAM files and BAM server. Specifically, DNA analysis of tumors was from the B16-F10 mouse melanoma line and matching normal tissue was blood DNA from C57bl / 6 parental mice. Expression results were screened by RNA sequencing of this tumor cell line. The found expressed neo-epitopes were further analyzed for binding affinity to murine MHC-I (here: Kb) and MHC-II (here: I-Ab). Following the further steps of dbSNP screening using the positional alignment of all neo-epitopes, followed by a weighting matrix and neural network prediction processing to generate scores representing the likelihood and / or strength of the presence of hydrophobic sequences or signal peptides, further analysis of the selected Binders (with an affinity equal to or less than 200 nM)...

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Abstract

Systems and methods are presented that allow for selection of tumor neoepitopes that are then used to generate a recombinant polytope that is optimized for proper trafficking and processing. In preferred methods, the polytope is encoded in a viral expression system that is used as a therapeutic agent.

Description

[0001] This application claims U.S. Provisional priority of the application, all of these provisional applications are hereby incorporated by reference. field of invention [0002] The field of the invention is improved compositions and methods for neoepitope-based immunotherapy, and in particular relates to the production of recombinant viral therapeutics for cancer treatment. Background technique [0003] The Background Description includes information useful in understanding the present invention. It is not an admission that any information provided herein is prior art or that any publication specifically or implicitly referenced is prior art with respect to the presently claimed invention. [0004] All publications and patent applications are herein 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. To the extent that a definition or usage of a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/86C12N7/00C07K14/47A61K35/17A61K35/761A61K39/00A61K47/50A61K48/00G16B20/20
CPCA61K39/0011A61K39/39A61K2039/5256A61K2039/57A61K2039/572C12N2710/10343A61P35/00A61P37/04A61P43/00G16B20/20C12N7/00C12N15/86C07K2319/01G16B20/00A61K39/001102C07K7/06C07K14/70539C07K14/70596C12N2710/10321C12N2710/10334C12N2840/002A61K2039/5254A61K2039/70C07K2319/06C07K2319/40C07K2319/95
Inventor 卡伊万·尼亚兹安德鲁·纽伦沙赫鲁兹·拉比扎德派翠克·松吉翁斯蒂芬·查尔斯·本茨
Owner 河谷细胞有限公司
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