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Chimeric antigen receptor specific for tumor cells

A chimeric antigen receptor, specific technology, applied in the direction of receptor/cell surface antigen/cell surface determinant, for targeting specific cell fusion, anti-tumor drugs, etc., can solve the unsatisfied medical treatment of other cancer types demand and other issues

Pending Publication Date: 2018-04-27
ミルテニイビオテックベーファーウントコーカーゲー
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although good treatment options are available for many cancer types, there are still unmet medical needs in other cancer types

Method used

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  • Chimeric antigen receptor specific for tumor cells
  • Chimeric antigen receptor specific for tumor cells
  • Chimeric antigen receptor specific for tumor cells

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0122] Example 1: Expression of targets on pancreatic cancer

[0123] Expression of CLA, CD142, CD73, CD49c, CD66c, CD104, CD318, and TSPAN8 on xenografted human pancreatic cancer cells indicated a strong abundance of these markers on pancreatic cancer cells, independent of the tumor microenvironment ( image 3 ). Furthermore, all markers were also reproducibly expressed at high levels on primary human pancreatic cancer cells (labeled Epcam+), but not on cells of healthy tumor-infiltrating leukocytes (labeled CD45+) or other healthy tissue-resident cell types (labeled is not double negative) on ( Figure 4 ). These results were further validated using immunohistochemistry-based detection of target expression in human pancreatic carcinoma ( Figure 5 ).

Embodiment 2

[0124] Example 2: Structure of a CAR that recognizes a pancreatic cancer-specific target

[0125] Adapters used can contain epitopes / tags that allow detection of the CAR, such as figure 1 shown in . Examples of epitopes / tags are YOL, cMYC or HIS. The pancreatic cancer target-specific binding fragment is derived from one or several antibodies specific for CLA, CD142, CD73, CD49c, CD66c, CD104, CD318 and / or TSPAN8. The hinge region may be derived from, for example, an IgG domain, CD8α or CD28, and may contain an epitope / tag that allows detection of the CAR. The transmembrane domain may be derived from eg CD8α or CD28, followed by one to three signaling domains. These domains may be derived from, for example, CD28, 4-1BB, OX40 or CD3ζ.

Embodiment 3

[0126] Example 3: Structure of a Dual CAR Recognizing a Pancreatic Cancer-Specific Target

[0127] This can be done by combining multiple antigen binding sites on one CAR molecule or by using multiple CAR molecules that are expressed in one cell and only function in combination, for example by using each CAR construct that is ineffective for cell activation when used alone signaling domains to address the recognition of two or more targets ( figure 2 ).

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PUM

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Abstract

The present invention is directed to ligand like a chimeric antigen receptor (CAR), comprising an antigen binding domain specific for one or more antigens selected from the group consisting of CLA, CD142, CD73, CD49c, CD66c, CD104, CD318 and TSPAN8; cell populations expressing such CARs and the use of the cell populations for cancer therapy.

Description

technical field [0001] The present invention relates to the use of ligands comprising antigen-binding domains specific for certain antigens, such as chimeric antigen receptors (CARs), and / or to engineered ligands provided with such ligands. Use of engineered cells for the treatment of human cancer. Background technique [0002] Cancer is a broad group of diseases involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors that invade adjacent parts of the body. Cancer can also spread to further parts of the body through the lymph system or bloodstream. There are more than 200 different cancers known to affect humans. Although good treatment options are available for many cancer types, there are still unmet medical needs in other cancer types. [0003] The technology of chimeric antigen receptors (CARs) may offer a promising avenue for adoptive cellular immunotherapy of cancer. Typically, a CAR comprises an antibody single...

Claims

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Application Information

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IPC IPC(8): C07K19/00C12N5/10A61K35/17A61P35/00
CPCC07K14/7051C07K16/18C07K16/2803C07K16/2839C07K16/2842C07K16/2896C07K16/36C12N5/0636C07K2317/622C07K2319/00C07K2319/03C07K2319/33C12N2510/00A61K39/4611A61K39/4644A61K39/4631A61K2039/852A61P35/00C07K2317/31C07K16/28C07K2319/20C07K2319/40A61K39/001129A61K47/65A61K35/17C07K14/70517C07K14/70521C07K14/70596
Inventor A.波西奥D.埃卡德特O.哈德特A.兹奥内克S.托缪克J.科勒
Owner ミルテニイビオテックベーファーウントコーカーゲー
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