CAR T-Cell and Modified CD200R Combination for Durable Cancer Response
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Solution Overview
Problem
Existing CAR T-cell therapies targeting CD30, CD15, and CD123 antigens in cancers like Hodgkin lymphoma and primary mediastinal non-Hodgkin lymphoma have modest responses and limited long-term remission, necessitating improved therapies that leverage antigens co-expressed with CD200.
Innovation Solution
Combining chimeric antigen receptors (CARs) targeting CD30, CD15, or CD123 with modified CD200 receptors (CD200Rs) to enhance T-cell function and improve therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR T-cells targeting CD30, CD15, or CD123 antigens are used, then T-cells can attach to cancer cells expressing these antigens, but the therapeutic response is modest and long-term remission is limited
Solution Approach 1:
The patent combines CAR T-cells with modified CD200R receptors into a dual-receptor system. The CAR component targets cancer-specific antigens (CD30, CD15, or CD123) for precise tumor recognition, while the modified CD200R component provides enhanced T-cell activation and persistence signals. This merging of two different receptor mechanisms resolves the contradiction by simultaneously improving immediate therapeutic response through antigen targeting and long-term remission through enhanced T-cell survival and persistence signals from the CD200R pathway.
Solution Approach 2:
The patent creates a composite T-cell receptor system by integrating CAR technology with modified CD200R receptors. This composite approach combines the antigen-specific binding capability of CARs with the immunomodulatory functions of CD200R, generating a T-cell product that exhibits both strong initial anti-tumor activity and improved long-term persistence. The composite nature of the dual-receptor system allows simultaneous optimization of both therapeutic response and durability of effect.
2Object-affected harmful factors
If CAR T-cell therapy is administered to patients with Hodgkin lymphoma and primary mediastinal non-Hodgkin lymphoma, then cancer cells can be targeted, but very few patients achieve long-term remission
Solution Approach 1:
The patent incorporates modified CD200R receptors that provide preliminary activation and survival signals to T-cells before they encounter the tumor. This preliminary priming through CD200R signaling enhances T-cell persistence and functional longevity, preparing the immune system for sustained anti-tumor activity. By establishing this preliminary protective and activating signal, the therapy addresses the duration problem before the therapeutic response even begins, enabling long-term remission.
Solution Approach 2:
The modified CD200R component acts as a feedback mechanism that continuously provides survival and activation signals to CAR T-cells during their interaction with the tumor microenvironment. This feedback loop ensures that T-cells receiving antigen signals through CAR also receive persistent survival signals through CD200R, preventing T-cell exhaustion and death. The feedback mechanism directly addresses the long-term remission limitation by maintaining T-cell viability and functionality throughout the therapeutic process.
Data Source
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AI summary
The present disclosure relates to a combination of a chimeric antigen receptor (CAR) and a modified CD200 receptor (CD200R). More in particular, a combination of a CAR targeting an antigen highly expressed in cancers which also typically express CD200, such as Hodgkin lymphoma, with a modified CD200R has been found useful in the treatment of such cancers. The present disclosure further relates to polynucleic acids, vectors, immune cells, pharmaceutical compositions encoding or comprising said combination, the same for use in the treatment of cancer and methods of preparation of said immune cells.