Cd79a chimeric antigen receptors

A chimeric antigen receptor, CD79A technology, applied in the improved composition, effective treatment of cancers expressing CD79A, improved anti-CD79A chimeric antigen receptor field, can solve the problems of limited success and unpredictable therapeutic efficacy

Pending Publication Date: 2021-02-12
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Attempts to use genetically modified cells expressing chimeric antigen receptors (CARs) have also had limited success
Additionally, the therapeutic efficacy of a given antigen-binding domain used in a particular CAR can be unpredictable: if the antigen-binding domain binds too strongly, the CAR T cells can induce massive cytokine release, leading to what is seen as a "cytokine storm." (cytokine storm)", and if the antigen-binding domain binds too weakly, CAR T cells may not show sufficient therapeutic efficacy in clearing cancer cells

Method used

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  • Cd79a chimeric antigen receptors

Examples

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example 1

[0516] Construction of anti-CD79A CAR

[0517] A CAR containing a humanized anti-CD79A scFv antibody was designed to contain the MND promoter, hinge and transmembrane domain (from CD8α) and CD137 co-stimulatory domain operably linked to anti-CD79A scFv, followed by intracellular signaling of the CD3ζ chain area. The anti-CD79A CAR contains a CD8α signal peptide (SP) sequence for surface expression on immune effector cells. Table 3 shows the identification, Genbank reference, source name, and cited documents of the different nucleotide segments of exemplary anti-CD79A CAR lentiviral vectors. Exemplary CD79A CAR polypeptide sequences are set forth in SEQ ID NOs: 25-30, and exemplary CD79A CAR polynucleotide sequences are set forth in SEQ ID NOs: 31-36.

[0518] table 3.

[0519]

[0520]

example 2

[0522] Evaluation of Human Anti-CD79A CAR T Cells

[0523] Chimeric antigen receptors (CARs) specific for CD79A (eg, SEQ ID NOs: 25, 27, 29, and 30) were evaluated with respect to CAR expression and biological activity against CD79A-expressing cells.

[0524] target antigen expression

[0525] In one experiment, K562 cells, Pfeiffer cells and Daudi target cells were interrogated for CD79A expression using an anti-CD79A antibody. Cells were incubated with CD79A antibody and expression was assessed by flow cytometry. CD79A expression was undetectable on K562 cells, moderately expressed on Pfeiffer cells, and highly expressed on Daudi cells. Figure 1A .

[0526] In another experiment, CD79A expression was measured on Daudi, NU-DUL-1 , SU-DHL-2 and Pfeiffer target cells using anti-CD79A antibody. Cells were incubated with CD79A antibody and expression was assessed by flow cytometry. CD79A expression was also highest on Daudi cells, followed by a gradual decrease on NU-DUL-1,...

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Abstract

The invention provides improved compositions for adoptive cell therapies for cancers that express CD79A.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Application No. 62 / 685,078, filed June 14, 2018, which is hereby incorporated by reference in its entirety. [0003] Statement Regarding the Sequence Listing [0004] The Sequence Listing associated with this application is provided in text format instead of a paper copy and is hereby incorporated by reference into this specification. The name of the text file containing the sequence listing is BLBD_100_01WO_ST25.txt. The text file is 64KB, was created on June 14, 2019, and was submitted electronically via EFS-Web at the same time as this specification. technical field [0005] The present invention relates to improved compositions and methods for treating cancer. More specifically, the present invention relates to improved anti-CD79A chimeric antigen receptors (CARs), genetically modified immune effector cells and the use of these comp...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61K39/44C07K16/28C07K16/30C07K14/705
CPCA61K39/395C07K16/28A61K39/44C07K16/30C07K2319/33C07K2319/03C07K16/2803C07K14/7051A61K2039/5156C07K2317/622C07K2317/70C07K2317/24A61K39/001129A61K2039/5158C07K14/70517C12N5/0636A61K35/17A61P35/00C07K2317/565C07K2319/02C12N2740/16043C12N2510/00A61K2039/505C07K14/70507C07K14/70578C07K2317/53C07K2317/56C12N15/86
Inventor 凯文·弗里德曼莫莉·里德·帕金斯
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