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Chimeric antigen receptors targeting cd37 and cd19

A chimeric antigen receptor, CD37 technology, applied in the direction of targeting specific cell fusions, antibodies, polypeptides containing localization/targeting motifs, etc., can solve poor treatment, PTCL clinical problems, treatment of T cell malignant Problems such as unproven tumor

Pending Publication Date: 2021-01-29
THE GENERAL HOSPITAL CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Despite recognition of its complex heterogeneity and discovery of a defect in recurrence, PTCL remains a clinical problem and poorly treated
While CAR T immunotherapy has demonstrated impressive clinical results in ALL and B-cell NHL, it has not proven successful in the treatment of T-cell malignancies

Method used

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  • Chimeric antigen receptors targeting cd37 and cd19
  • Chimeric antigen receptors targeting cd37 and cd19
  • Chimeric antigen receptors targeting cd37 and cd19

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0219] Example 1. Primary human T cell culture

[0220] For primary T lymphocyte expansion, bulk human T cells (day 0) were activated using anti-CD3 / CD28 Dynabeads (Life Technologies) and subsequently transduced 24 hours later with a CAR-encoding lentiviral vector. From day 0 of culture, culture T cells in medium supplemented with 20 IU / ml rhIL-2 and count them by counting every 2-3 days at 0.5x10 6 T cells were maintained at a constant cell concentration per mL. For functional assays, CAR T cells were cryopreserved on days 8–10 in culture and stimulated with antigen or injected into mice immediately after thawing.

Embodiment 2

[0221] Example 2. Cell lines and culture conditions

[0222] JEKO-1, RAJI and wild-type parental K562 cells were purchased from American Type Culture Collection (ATCC). K562 cells were engineered to express CD37 and CD19 (K562-CD37-CD19). For some assays, cell lines were engineered to constitutively express click beetle green (CBG) luciferase / enhanced GFP (eGFP), and then expressed in a FACSAria (BD ) to obtain a population with a purity ≥ 99% (CBG-GFP+). Cell lines were grown in RPMI medium containing 10% fetal bovine serum (FBS), penicillin and streptomycin.

Embodiment 3

[0223] Example 3. Flow Cytometry

[0224]The following antibody was used: CD37-APC (clone MB-1 ), CD37-BV711 (clone MB-371, BD ), CD19-Pacific Blue (clone HIB19, ), CD19-FITC (clone 4G7, BD), CD5-BUV737 (clone UCHT2, BD), CD20-APC Cy7 (clone 2H7, ), CD79b-PE (clone CB3-1, ), CD3-BV786 (clone SK7, BD), CD3-BV605 (clone OKT3, ), CD45-PeCy7 (clone HI30, ), CD16-PE (clone B73.1, ), CD14-PacificBlue (clone HCD14, ), CD56-APC (clone HCD56, ), CD33-BV510 (clone P67.6, ), CD107a-AF700 (clone H4A3, BD ), CD69-APC (clone FN50, ) and IFNγ-FITC (clone GZ-4, ). Cells were stained for 30 min at 4°C in the dark and washed twice in PBS containing 2% FBS. DAPI was added to gate live cells prior to acquisition. Measured using antibody bound per cell (ABC) and using Quantum TM Antigen density was calculated by Simply Cellular (Bangs Laboratories).

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PUM

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Abstract

The invention provides bispecific chimeric antigen receptors (CARs) targeting CD37 and CD19, as well as related molecules, immune cells including the same, compositions thereof, and their methods of use. The invention further provides methods for treating a disease or disorder, e.g., a cancer.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of U.S. Provisional Application No. 62 / 688,775, filed June 22, 2018, and U.S. Provisional Application No. 62 / 757,562, filed November 8, 2018, the contents of which are hereby incorporated by reference in their entirety . [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 June 19, 2019 is named 51295-018WO3_Sequence_Listing_6.19.19_ST25 and is 56,545 bytes in size. Background technique [0005] Immunotherapy uses a patient's immune system to treat diseases, such as cancer, autoimmune diseases, or plasma cell disorders. Adoptive cell transfer utilizes antigen-specific immune cells, such as T cells, to treat such diseases. Immune cells used in such therapy can be modified to exhibit a desired specificity, for example by expr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/17A61K35/13C07K16/28
CPCA61P35/00C07K16/2803C07K16/2896C07K2319/03C07K2319/33C07K2317/73A61K2039/505C12N2510/00C07K2317/622C07K2317/31C07K14/7051A61K2039/804A61K39/4613C12N5/0636A61K2239/29A61K39/4631C12N5/0646A61K39/464412A61K39/4611A61K39/464429A61K2239/48A61K2239/31A61K2239/38C07K14/70517C07K14/70578C07K2317/53C07K2317/56C07K2319/02
Inventor M·V·毛斯
Owner THE GENERAL HOSPITAL CORP