Anti-ROR1 chimeric antigen receptors

A chimeric antigen receptor, antibody technology, applied in the direction of antibodies, antibody medical components, antibody mimics/scaffolds, etc., can solve the problem of lack of ROR1 expression in adult tissues

Active Publication Date: 2018-06-08
EUREKA THERAPEUTICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007]Although ROR1 is selectively overexpressed in several solid and ...

Method used

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  • Anti-ROR1 chimeric antigen receptors

Examples

Experimental program
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Effect test

example 1

[0657] Construction of anti-ROR1 CAR

[0658] CARs containing humanized anti-ROR1 scFv antibodies were designed to contain the MND promoter operably linked to anti-ROR1 scFv, hinge and transmembrane domains from CD8α and CD137 costimulatory domains, followed by CD3ζ The intracellular signaling domain of the chain. figure 1 The anti-ROR1 CAR includes a CD8α signal peptide (SP) sequence for surface expression on immune effector cells. Table 3 shows the identity, gene bank reference, source nomenclature, and cited documents of various nucleotide fragments of exemplary anti-ROR1 CAR lentiviral vectors.

[0659] table 3.

[0660]

[0661]

example 2

[0663] Evaluation of Human Anti-ROR1 CAR T Cells

[0664] Evaluation of transduction efficiency, CAR expression, and ROR1 biological activity.

[0665] Anti-ROR1 CAR molecules were constructed using sequences from scFv isolated from a human phage display library. CAR T cells were generated following lentiviral transduction of primary human T cells. Four CAR candidates were selected for further study after an initial high-throughput screen consisting of in vitro assays analyzing CAR expression and ROR1-specific T cell activity. Anti-ROR1 CAR2 includes the variable chain set forth in SEQ ID NO:7 and SEQ ID NO:8; anti-ROR1 CAR4 includes the variable chain set forth in SEQ ID NO:63 and SEQ ID NO:64; anti-ROR1 CAR6 includes The variable chain set forth in SEQ ID NO:15 and SEQ ID NO:16 and the anti-ROR1 CAR15 includes the variable chain set forth in SEQ ID NO:159 and SEQ ID NO:160. The transduction efficiency, CAR expression, and ROR1 biological activity of anti-ROR1 CAR T cells...

example 3

[0672] Evaluation of additional human anti-ROR1 CAR T cells

[0673] Evaluation of transduction efficiency, CAR expression, and ROR1 biological active.

[0674] Anti-ROR1 CAR molecules were constructed using sequences from scFv isolated from a human phage display library. CAR T cells were generated following lentiviral transduction of primary human T cells. Five CAR candidates were selected for further study following an initial high-throughput screen consisting of in vitro assays analyzing CAR expression and ROR1-specific T cell activity. The anti-ROR1 CAR50 includes the variable chain set forth in SEQ ID NO:255 and SEQ ID NO:256; the anti-ROR1 CAR53 includes the variable chain set forth in SEQ ID NO:271 and SEQ ID NO:272; the anti-ROR1 CAR54 includes the variable chain set forth in SEQ ID NO:271 and SEQ ID NO:272; The variable chains in SEQ ID NO:279 and SEQ ID NO:280; the anti-ROR1 CAR60 includes the variable chains set forth in SEQ ID NO:319 and SEQ ID NO:320; and the a...

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Abstract

The invention provides improved compositions for adoptive cell therapies for cancers that express ROR1.

Description

[0001] Cross References to Related Applications [0002] This application is based on 35 U.S.C. § 119(e) petitions U.S. Provisional Application No. 62 / 322,414 filed April 14, 2016, U.S. Provisional Application No. 62 / 307,928 filed March 14, 2016, July 2015 U.S. Provisional Application No. 62 / 193,514, filed May 16, and U.S. Provisional Application No. 62 / 163,272, filed May 18, 2015, each of which is incorporated herein by reference in its entirety middle. [0003] Statement Regarding Sequence Listing [0004] The Sequence Listing associated with this application is provided in text format in lieu of hard copy and is hereby incorporated by reference into this specification. The name of the text file containing the sequence listing is BLBD_050_04WO_ST25.txt. The text file is 205KB, was created on May 16, 2016, and was submitted electronically through EF-Web, and the instructions were filed at the same time. technical field [0005] The present invention relates to improved...

Claims

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Application Information

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IPC IPC(8): C07K14/705C07K16/28C07K16/30C07K14/735A61K39/00
CPCC07K14/7051C07K16/2803A61K2039/505C07K2317/622C07K2317/73C07K2319/03C07K2319/74A61P35/02A61K39/001102C07K16/30
Inventor 理查德·摩根罗伯特·西科尔斯基布莱恩·黄艾玛·曼斯特勒路易斯·博尔赫斯刘诚许奕阳
Owner EUREKA THERAPEUTICS INC
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