CAR Cells Targeting SIGLEC15 for Solid Tumor Therapy
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Solution Overview
Problem
Current cancer treatment methods, including surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy, often fail to effectively treat advanced cancer patients and are associated with significant side effects and a poor quality of life.
Innovation Solution
Development of chimeric antigen receptor (CAR) cells that express an extracellular domain binding specific antigens such as SIGLEC15, SLC6A3, KISS1R, and others, which are selectively expressed on tumor cells, allowing for targeted cancer therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional cancer treatments (surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy) are used, then treatment coverage is broad, but treatment effectiveness for advanced patients is poor and side effects are significant
Solution Approach 1:
The patent introduces CAR-modified immune cells as an intermediary between the patient's immune system and tumor cells. These engineered cells express chimeric antigen receptors that specifically recognize tumor-associated antigens, enabling targeted destruction of cancer cells while preserving normal tissues. This intermediary approach overcomes the limitations of conventional therapies by providing selective tumor killing without broad toxic effects.
Solution Approach 2:
The invention applies local quality by designing CAR receptors with specific antigen-binding domains that recognize particular tumor-associated antigens (such as SIGLEC15, SLC6A3, KISS1R). This specificity ensures that the therapeutic effect is concentrated on tumor cells expressing these antigens, while normal cells lacking or having low levels of these antigens are spared, thereby reducing systemic side effects.
2Productivity
If CAR cells targeting highly expressed antigens are used, then tumor killing efficiency is high, but normal cells are also damaged causing life-threatening complications
Solution Approach 1:
The patent selects tumor-associated antigens that exhibit differential expression patterns - highly expressed on tumor cells but low or absent on normal cells. Examples include SIGLEC15 in urothelial cancer, SLC6A3 in renal cancer, and KISS1R in renal and pancreatic cancers. This expression differential enables the CAR cells to concentrate their killing effect on tumor cells while sparing normal tissues, resolving the contradiction between efficacy and safety.
Solution Approach 2:
The invention changes the selection parameter from commonly targeted antigens to less conventional tumor-associated antigens with more favorable expression profiles. By selecting antigens like ACPP in prostate cancer or MUC16 in ovarian cancer that have higher tumor-to-normal tissue expression ratios, the therapy achieves better selectivity and reduced off-target effects while maintaining potent anti-tumor activity.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The use of CAR cells specifically binding to tumor-associated antigens enables effective killing of cancer cells while sparing normal cells, potentially improving treatment outcomes and reducing side effects.
Implementation Method 1
the CAR comprises an extracellular domain, a transmembrane domain, and an intracellular domain, wherein the extracellular domain of the CAR binds an antigen of a solid tumor
Data Source
AI summary
The compositions and methods described herein are directed to treating solid tumor using CAR T therapy. The compositions include CAR comprising an extracellular domain that binds a siglec protein or a receptor that binds the peptide hormone kisspeptin.