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

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 ...

AI Technical Summary

Benefits of technology

The patent describes a method to improve the function of T cells and NK cells, which are important components of the immune system. This method involves using a combination of a ketogenic diet and CAR-DC therapy to enhance the T cells' ability to fight tumors. The ketogenic diet helps to lower the levels of lactate, which is a molecule that can promote tumor growth. By reducing lactate levels, the T cells become more responsive to tumor-related signals and can better fight tumors. The CAR-DC therapy involves taking T cells from a patient and modifying them to recognize and attack tumor cells. When these modified T cells are combined with a ketogenic diet, they become even more effective at fighting tumors. This method can also be used in combination with other chemotherapy drugs to further enhance the treatment's effectiveness.

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-regulated or mutated in response to treatment resulting in tumor evasion.

Since current CAR T cells recognize only one target antigen, such changes in tumors negate the therapeutic effects.

Finally, CAR T cells react with target antigen weakly expressed on non-tumor cells, potentially causing severe adverse effects.

And although ongoing studies are focused on generating methods to shut off CAR T cells in vivo this system has yet to be developed and might pose additional inherent challenges.