Anti-CD70 Chimeric Receptor Cells for Low-Antigen Tumor Targeting
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Solution Overview
Problem
Existing cell-based immunotherapies for treating solid tumors, such as renal cell carcinoma, pancreatic cancer, and ovarian cancer, face challenges with treatment failure and relapses due to low expression or heterogeneity of tumor antigens like CD70, leading to incomplete tumor eradication.
Innovation Solution
Development of TCR-like fusion molecules targeting CD70, which are administered to patients after detecting CD70 polynucleotides or treated with Ezh2 inhibitors to enhance CD70 expression, combined with cells expressing chimeric antigen receptors (CARs) and co-stimulatory ligands to improve tumor targeting and eradication.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional cell-based immunotherapies are used to treat solid tumors, then treatment can be initiated, but treatment failure and relapses occur due to low expression or heterogeneity of tumor antigens like CD70
Solution Approach 1:
The patent applies preliminary action by using Ezh2 inhibitors to pre-treat tumors and enhance CD70 expression before administering CAR T cells. This ensures that when the immunotherapy is delivered, the tumor cells have already been primed to express higher levels of the target antigen, thereby improving the reliability of treatment efficacy rather than attempting to overcome low antigen expression during the treatment process itself
Solution Approach 2:
The patent changes the parameter of CD70 expression level on tumor cells by using Ezh2 inhibitors. By modulating the expression parameter of the target antigen before immunotherapy, the system transforms tumors with low antigen density into those with high antigen density, directly addressing the contradiction between treatment reliability and antigen quantity
2Productivity
If CAR T cells are administered to target CD70, then immune response is activated, but treatment fails when CD70 expression is low or heterogeneous
Solution Approach 1:
The patent uses Ezh2 inhibitors as a preliminary action to enhance CD70 expression on tumor cells before CAR T cell administration. This ensures that when the immune response is activated, there is sufficient antigen target available, thereby maintaining both high immune response activity and reliable tumor eradication
Solution Approach 2:
The Ezh2 inhibitor acts as an intermediary substance that facilitates the interaction between CAR T cells and tumor cells. By enhancing CD70 expression, the intermediary (Ezh2 inhibitor) ensures that the immune response has adequate targets to act upon, bridging the gap between activating immune response and achieving reliable tumor eradication
3Adaptability or versatility
If CD70 polynucleotide detection is performed to guide treatment, then treatment can be targeted, but additional detection steps and Ezh2 inhibitor treatment are required
Solution Approach 1:
The patent implements feedback by using CD70 polynucleotide detection to guide treatment decisions. The detection result provides feedback on whether the tumor expresses CD70, and based on this feedback, the system determines whether to proceed with Ezh2 inhibitor treatment and CAR T cell administration, creating a customized feedback-driven treatment protocol
Solution Approach 2:
The CD70 polynucleotide detection serves as a preliminary screening action before initiating the full treatment protocol. By performing this detection first, the system identifies suitable candidates for the subsequent Ezh2 inhibitor and CAR T cell treatment, allowing for customized treatment planning while managing the complexity through a clear sequential workflow
Data Source
AI summary
The presently disclosed subject matter provides cells, compositions and methods for enhancing immune responses toward tumor antigens. It relates to cells comprising a first antigen-recognizing receptor that targets CD70. These cells have improved activity and/or efficiency.