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Compositions and methods for treating cancer with Anti-ror1 immunotherapy

An antigen and antibody technology, applied in the field of cancer, can solve problems such as patient failure

Pending Publication Date: 2020-10-02
LENTIGEN TECH INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Despite reports of high responses in CD19 CAR-T trials, at least 20% of patients had recent failures (Davis KL, Mackall CL, 2016, Blood Advances 1:265-268)

Method used

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  • Compositions and methods for treating cancer with Anti-ror1 immunotherapy
  • Compositions and methods for treating cancer with Anti-ror1 immunotherapy
  • Compositions and methods for treating cancer with Anti-ror1 immunotherapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0291] Isolation of ROR1-specific binders from fully human phage and yeast (Yeast)-displayed scFv libraries

[0292] Materials and methods

[0293] a) Generation of fully human ScFc (ScFv with Fc domain for analysis) binders to human ROR1

[0294] An initial human scFv (recombinant single-chain variable fragment of immunoglobulin) phage display library (approximate diversity, 10) constructed from peripheral blood B cells of 50 healthy donors 10 Unique specificity) (Z.Y. Zhu and D.S. Dimitrov, unpublished data) was used to select scFv of recombinant human ROR1 protein. will be 10 12 Amplified libraries of phage-displayed scFv were incubated with 5, 3, and 1 μg of coated ROR1 in 5 × 100-μl volumes, homogenized at room temperature during the first, second, and third rounds of biopanning, respectively. Distribute in 5 wells of a 96-well plate for 2 hours. After each round of incubation, the wells were washed with phosphate-buffered saline (PBST) containing 0.05% Tween 20 (5 wa...

Embodiment 2

[0302] CAR expressing anti-ROR1 fully human binding sequence.

[0303] Homo sapiens ROR1 (receptor tyrosine kinase-like orphan receptor 1) is a well-studied carcinoembryonic cell surface glycoprotein that is involved in chronic lymphocytic leukemia (CLL) and various solid tumors such as lung adenocarcinoma Carcinoma, sarcoma, or a subset of carcinomas). A phase I study of the anti-ROR1 antibody UC-961 (cetuzumab) in relapsed or refractory chronic lymphocytic leukemia is currently underway (sponsor, Thomas Kipps, NCT02222688). The results of this first-of-its-kind study are pending. Also in early stages is a phase 1 clinical trial with a CAR-T specific for ROR1 (sponsor, Fred Hutchinson Cancer Research Center, NCT02706392). We have included published ROR1 binders as our controls (LTG1943, LTG2527) (see Hudecek et al., 2013, Clin Cancer Res 19:3153-3164) to benchmark our studies and show the efficacy of our constructs. active. Given recent advances in T cell-based therapy, i...

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Abstract

Chimeric antigen receptors containing ROR1 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions,relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.

Description

[0001] Cross References to Related Applications [0002] This application claims priority benefit under 35 U.S.C. Section 119(e) to U.S. Provisional Patent Application No. 62 / 581,284, filed November 3, 2017, the entire contents of which are incorporated herein by reference. [0003] sequence listing [0004] This application contains a Sequence Listing that has been filed electronically in ASCII format and is hereby incorporated by reference in its entirety. The ASCII copy created on October 25, 2018 is named SequenceListing.txt and is 90.0 kilobytes in size. [0005] Statement Regarding Federal Funding for Research and Development [0006] This invention was made in the execution of a collaborative research and development agreement with the National Institutes of Health, a division of the Department of Health and Human Service. The US Government has certain rights in this invention. technical field [0007] The present application relates to the field of cancer, in parti...

Claims

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Application Information

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IPC IPC(8): A61K35/17A61K38/00A61P31/00A61P31/04A61P31/10
CPCC07K14/7051C07K2319/03C12N2740/16043A61P35/00A61K38/1774C07K14/70517C07K16/28C12N15/62C12N15/113C07K14/15C07K14/70589C07K14/70521C07K14/70525C07K14/70535C07K14/70532C07K14/70575C07K14/70514
Inventor 里马斯·J·奥伦塔什迪娜·施奈德博罗·德罗普利奇迪米特尔·S·迪米特罗夫朱忠玉
Owner LENTIGEN TECH INC
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