CD70 CAR with CD27 Domain for Tumor Elimination
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Solution Overview
Problem
Current cancer treatments, particularly for renal cell carcinoma (RCC), glioblastoma, non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), diffuse large-B-cell lymphoma, and follicular lymphoma, have poor prognosis and an unmet need for additional effective therapies.
Innovation Solution
Development of a chimeric antigen receptor (CAR) with antigenic specificity for CD70, comprising an antigen binding-transmembrane domain with a CD27 amino acid sequence lacking certain intracellular T cell signaling domains, combined with 4-1BB and CD3ζ intracellular T cell signaling domains, to target and destroy CD70-expressing cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional cancer treatments are used, then treatment coverage is provided, but prognosis remains poor and effectiveness is insufficient
Solution Approach 1:
The patent introduces chimeric antigen receptors (CARs) as intermediary molecules that bridge T cells and cancer cells expressing CD70. The CAR construct includes an antigen-binding domain specific to CD70, a transmembrane domain, and intracellular signaling domains, serving as a mediator that redirects T cell specificity toward cancer cells while enhancing their ability to recognize and eliminate tumors that are refractory to conventional therapies
Solution Approach 2:
The patent modifies the T cell's surface receptor parameters by engineering CARs with specific structural components: variable domains from antibodies or T cell receptors for antigen recognition, combined with signaling domains from T cell receptors. This parameter change in the receptor structure enables T cells to recognize and respond to cancer cells that do not present antigens through conventional MHC pathways, thereby improving treatment effectiveness for refractory cancers
2Productivity
If cancer treatments target tumor cells, then tumor burden is reduced, but damage to normal tissues occurs
Solution Approach 1:
The patent applies local quality by engineering CARs with antigen-binding domains that specifically recognize CD70 expressed on cancer cells. The variable domains are selected to bind with high affinity and specificity to CD70, enabling T cells to distinguish cancer cells from normal cells based on the localized presence of the CD70 antigen, thereby reducing off-target effects on normal tissues while maintaining effective tumor cell killing
Data Source
AI summary
The invention provides a chimeric antigen receptor (CAR) having antigenic specificity for CD70, the CAR comprising: an antigen binding-transmembrane domain comprising a CD27 amino acid sequence lacking all or a portion of the CD27 intracellular T cell signaling domain; a 4-1BB intracellular T cell signaling domain; a CD3ζ intracellular T cell signaling domain; and optionally, a CD28 intracellular T cell signaling domain. Nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.