Chimeric antigen receptor dendritic cell (car-dc) for treatment of cancer

a dendritic cell and chimeric antigen technology, applied in the field of genetics, immunology and medicine, can solve the problems of high cost and labor-intensive tasks associated with identifying and engineering scfvs against a variety of tumor antigens, and the response rate is disappointingly low

Inactive Publication Date: 2017-06-01
MYELOID THERAPEUTICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Despite the intellectual appeal of peptide based cancer vaccines, the response rate has been disappointingly low.
Despite of the promise that CAR T cells might have in treating cancer patients there are several limitations to the generalized clinical application of CAR T cells.
Second, the financial cost and labor-intensive tasks associated with identifying and engineering scFvs against a variety of tumor antigens poses a major challenge.
Third, tumor antigens targeted by CAR could be down-

Method used

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Embodiment Construction

[0011]Chimeric antigen receptor (CAR) cellular therapeutics have revolutionized the treatment of B cell malignancies achieving stunning success rates. Unfortunately, solid tumors have yet to benefit from this treatment. Additionally, patients treated with CAR-T cells lack B cells for the rest of their lives, as well as having the possibility of tumor lysis syndrome. This is in part due to the permanence of the CAR-T cells in the patients after treatment. The current invention applies the use of CAR technology to monocytes with the purpose of inducing differentiation to dendritic cells (DC) subsequent to contact with tumor antigens. Given that monocytes have a fixed mitotic index, fears of permanent manipulation of the host are diminished.

[0012]“Treating a cancer”, “inhibiting cancer”, “reducing cancer growth” refers to inhibiting or preventing oncogenic activity of cancer cells. Oncogenic activity can comprise inhibiting migration, invasion, drug resistance, cell survival, anchorage...

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Abstract

The current invention provides monocytic cells transfected with chimeric antigen receptor (CAR) to selectively home to tumors and upon homing differentiate into dendritic cells capable of activating immunity which is inhibitory to said tumor. In one embodiment of the invention, monocytic cells are transfected with a construct encoding an antigen binding domain, a transcellular or structural domain, and an intracellular signaling domain. In one specific aspect of the invention, the antigen binding domain interacts with sufficient affinity to a tumor antigen, capable of triggering said intracellular domain to induce an activation signal to induce monocyte differentiation into DC.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]This application claims the benefit of U.S. Provisional Application No. 62 / 118,027 filed on Feb. 19, 2015, the contents of which are incorporated herein by reference in its entirety.FIELD OF THE INVENTION[0002]The present disclosure generally relates to the fields of genetics, immunology and medicine. The invention pertains to the field of immunotherapy, more specifically the invention pertains to the utilization of monocytes that have been manipulated to home to tumor cells and upon binding to tumor antigens differentiating into monocytes with cytotoxic properties to tumors, or dendritic cells.BACKGROUND OF THE INVENTION[0003]The immune system possesses the power to cure cancers based on published reports of immunologically mediated spontaneous regressions, which have been document in colon, lung, melanoma, liver, breast. Intriguingly, spontaneous regression clinically, as well as in an animal model of spontaneous regression, seems to be ...

Claims

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Application Information

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IPC IPC(8): A61K35/15A61K39/395A61K38/17C12N5/0786
CPCA61K35/15C12N5/0645C12N2510/00A61K38/177A61K39/39558C07K16/00C07K16/30C07K16/32C07K2317/622C07K2319/03C07K2319/33C12N2501/599
Inventor WAGNER, SAMUEL C.ICHIM, THOMAS E.SZYMANSKI, JULIA S.KESARI, SANTOSHPATEL, AMIT N.MINEV, BORIS
Owner MYELOID THERAPEUTICS INC
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