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Compositions and methods comprising prostate stem cell antigen (PSCA) chimeric antigen receptors (CARS)

A technology of chimeric antigen receptors and stem cell antigens, applied in receptors/cell surface antigens/cell surface determinants, chemical instruments and methods, antibody mimics/scaffolds, etc., can solve incurable androgen-independent diseases And other issues

Pending Publication Date: 2022-07-08
THE TRUSTEES OF THE UNIV OF PENNSYLVANIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although hormone ablation therapy can palliate these patients, most inevitably develop incurable androgen-independent disease

Method used

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  • Compositions and methods comprising prostate stem cell antigen (PSCA) chimeric antigen receptors (CARS)
  • Compositions and methods comprising prostate stem cell antigen (PSCA) chimeric antigen receptors (CARS)
  • Compositions and methods comprising prostate stem cell antigen (PSCA) chimeric antigen receptors (CARS)

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Embodiment 1

[0450] Herein, various prostate stem cell antigen (PSCA)-specific CARs were generated. The antigen binding domain is derived from a humanized anti-PSCA antibody (2B3) (US Patent Publication No. US2010 / 0297004, the contents of which are incorporated herein by reference in their entirety) ( figure 1 ). Use 2B3 scFv in combination with various intracellular domains, including 4-1BB and CD3ζ (2B3.BBZ CAR), CD28 and CD3ζ (2B3.28Z CAR), ICOS and CD3ζ (2B3.ICOSZ CAR), and mutated ICOS (ICOS .YMNM CAR) and CD3ζ (2B3.ICOS.YMNM CAR). PSCA CARs containing the PD1-CD28 switch receptor, the TGFbR / IL12R switch receptor, and the dominant negative receptor (TGFbRDN) were also generated. A dual CAR containing specificity for PSCA and PSMA has also been developed. PSCACAR is also used in combination with bispecific antibodies such as aPD-L1 / CD28 or aTGFbRII-CD28.

[0451] CAR expression was measured in T cells co-electroporated with in vitro transcribed RNA of PSCA CAR (2B3.BBZ) and PMSA CA...

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Abstract

The present disclosure provides modified immune cells or precursors thereof (e.g., T cells) comprising a chimeric antigen receptor (CAR) capable of binding to human PSCA. Also provided are CARs capable of binding to human PSCA, as well as nucleic acids encoding the same. Provided herein are bispecific CARs capable of binding to human PSCA and human PSMA, nucleic acids encoding them, and modified immune cells comprising them. A modified immune cell comprising a PSMA CAR and a PSCA CAR is also provided. Compositions and methods of treatment are also provided.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS [0002] This application enjoys priority under 35 U.S.C. §119(e) to U.S. Provisional Patent Application No. 62 / 985,808, filed March 5, 2020, and U.S. Provisional Patent Application No. 62 / 898,896, filed September 11, 2019, in This is incorporated herein by reference in its entirety. Background technique [0003] Prostate cancer is the most common cancer diagnosis and the second leading cause of cancer-related death among men in the United States. Despite recent advances in the detection and treatment of localized disease, significant challenges remain in the management of the disease. Current diagnostic modalities are limited, lack specificity and fail to predict which patients are at risk for developing metastatic disease. Prostate-specific antigen (PSA), although useful in identifying men who may have prostate cancer, is often elevated in men with benign prostatic hyperplasia, prostatitis, and other non-malignant conditions. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K19/00
CPCA61P35/00C07K14/7051C07K2319/03A61K39/001193C07K16/3069C07K2319/30C07K2317/622A61K2039/5156C07K2317/31C07K16/2818C07K16/2863A61K39/001195A61K2039/70A61K35/17A61K39/4611A61K39/4631A61K39/4644A61K35/14C12N15/85C07K14/70521C07K14/70517
Inventor 赵阳兵
Owner THE TRUSTEES OF THE UNIV OF PENNSYLVANIA
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