CAR Tolerance Peptides for Adoptive Cell Therapy
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Solution Overview
Problem
Adoptive cell therapies using engineered cells expressing recombinant receptors, such as chimeric antigen receptors (CARs), face limitations due to immune responses that reduce the exposure and persistence of these cells, leading to decreased efficacy and potential toxicity from immunosuppressive treatments.
Innovation Solution
Administering peptides comprising portions of the CAR's immunogenic regions, specifically designed to induce tolerance in subjects, thereby reducing immune responses against the CAR-expressed cells, which can be done prior to or alongside the administration of CAR-expressing cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If adoptive cell therapy using CAR-expressing cells is administered, then treatment efficacy is improved, but immune responses against the CAR reduce cell persistence and exposure
Solution Approach 1:
The patent applies preliminary action by administering peptides containing CAR immunogenic epitopes before CAR cell administration to pre-induce immune tolerance. This preparatory step modifies the subject's immune system in advance to recognize and tolerate the CAR-expressing cells, preventing subsequent immune-mediated cell clearance and thereby extending cell persistence while maintaining treatment efficacy
Solution Approach 2:
The patent uses peptides containing CAR epitopes as intermediary substances that mediate between the immune system and CAR-expressing cells. These peptides act as bridges to induce regulatory T cells and suppressor cells that actively protect the CAR cells from immune attack, thereby extending their persistence in the body without compromising their therapeutic function
2Duration of action of stationary object
If immune responses against CAR are reduced through conventional methods, then cell persistence may improve, but toxic immunosuppressive treatments are required
Solution Approach 1:
The patent converts the potentially harmful immune response into a beneficial tolerogenic response by using peptides to redirect immune system activity. Instead of suppressing the immune system with toxic drugs, the peptides harness immune mechanisms to generate regulatory T cells and suppressor cells that specifically protect CAR cells, transforming the immune system from a harmful force into a protective mechanism
Solution Approach 2:
The patent introduces peptides as intermediary substances that mediate immune tolerance without requiring toxic immunosuppressive drugs. These peptides serve as safe carriers that deliver CAR epitopes to the immune system, inducing tolerance through natural immunological mechanisms rather than chemical suppression, thereby avoiding drug toxicity while extending cell persistence
3Productivity
If CAR-expressing cells are administered without tolerance induction, then treatment can begin immediately, but immune rejection reduces cell exposure
Solution Approach 1:
The patent applies preliminary action by administering CAR epitope-containing peptides for several days before CAR cell administration to pre-induce immune tolerance. This advance preparation ensures that when CAR cells are introduced, the immune system is already primed to tolerate them, preventing rapid clearance and ensuring adequate cell exposure and expansion without delaying treatment initiation
Data Source
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AI summary
Provided are methods of administering peptides containing portions of or corresponding to an agent to be administered, such as a cell or molecule expressed by such cell such as a recombinant protein such as a chimeric receptor. In some embodiments, the administration is in conjunction with treatment methods employing the agent, e.g., cell or chimeric receptor, such as adoptive cell therapy methods. The chimeric receptor can be a chimeric antigen receptor (CAR). The peptides contain an epitope of the recombinant receptor and, in some embodiments, are capable of downregulating or reducing immune responses against the chimeric receptor, such as CAR. Also provided are such peptides and compositions that can induce tolerance to an agent such as a chimeric receptor, such as a CAR.