CD117 Isoforms for Selective Cancer Cell Targeting
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Solution Overview
Problem
Current immunotherapies targeting CD117 in cancer treatment often lack specificity, leading to the destruction of both malignant and normal hematopoietic cells, resulting in severe side effects and functional defects in engineered cells.
Innovation Solution
Development of CD117 isoforms with specific amino acid substitutions that maintain normal function while being immunologically distinguishable from the wild-type CD117, allowing for targeted depletion of malignant cells without affecting normal cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional immunotherapies target CD117 to treat cancer, then malignant cells are eliminated, but normal hematopoietic cells are also destroyed causing severe side effects
Solution Approach 1:
The patent applies local quality by creating a heterogeneous population of cells where only a subset (those with wild-type CD117) is targeted by the immunotherapy, while cells with mutated CD117 variants are spared. This allows selective elimination of malignant cells expressing the target antigen while preserving normal cells or malignant cells with alternative antigen profiles.
Solution Approach 2:
The patent utilizes parameter changes by altering the antigenic properties of CD117 through amino acid mutations. By changing the molecular structure of the surface protein, the patent creates variants that are no longer recognized by anti-CD117 antibodies, thereby modifying the targetability parameter of different cell populations and enabling selective therapy.
2Reliability
If CD117 is targeted for immunotherapy, then cancer cells are killed, but normal hematopoiesis is depleted
Solution Approach 1:
The patent applies preliminary action by pre-modifying a subset of cells to express mutated CD117 variants before immunotherapy administration. This advance preparation ensures that when anti-CD117 therapy is given, these pre-modified cells are already protected from depletion, preserving hematopoietic function while still allowing cancer cells with wild-type CD117 to be eliminated.
Solution Approach 2:
The patent creates functional heterogeneity within the cell population by introducing CD117 mutations in only some cells. This local differentiation in antigen expression allows the immunotherapy to selectively affect cancer cells while leaving a reservoir of protected hematopoietic cells intact to maintain normal blood cell production.
3Productivity
If engineered cells are used to restore hematopoiesis, then normal blood cell production is regenerated, but the cells may still be targeted by anti-CD117 therapy
Solution Approach 1:
The patent applies parameter changes by modifying the antigenic parameters of CD117 in engineered hematopoietic cells through amino acid mutations. This structural modification changes the recognition profile of the surface protein, allowing regenerated hematopoietic cells to escape detection and targeting by anti-CD117 immunotherapies while maintaining normal cellular function.
Solution Approach 2:
The patent uses copying by creating mutant versions of the CD117 protein that replicate the essential functional properties of the wild-type protein (ligand binding, signal transduction) while altering the antigenic epitopes. This allows engineered cells to copy the protective feature of antigenic variation while maintaining physiological function.
Data Source
AI summary
The present disclosure relates to the use of cells having discernible surface protein with engineered or naturally occurring mutation(s) but functional surface protein for use in therapy. The present invention also relates to the use of cells having discernible CD117 surface protein variants but functional surface protein for use in therapy, in particular adoptive cell therapy.