hK2-Targeting CARs for Prostate Cancer Specificity
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Solution Overview
Problem
Current cancer therapies, particularly for prostate cancer, lack effective targeting mechanisms to specifically eliminate cancer cells while minimizing harm to healthy tissues, and there is a need for improved treatments beyond androgen depletion therapy for metastatic prostate cancer.
Innovation Solution
Development of chimeric antigen receptors (CARs) that target human Kallikrein-2 (hK2), comprising specific antigen-binding domains, transmembrane domains, and intracellular signaling domains, engineered to be expressed in immune cells to enhance their specificity and cytotoxic activity against hK2-expressing cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If traditional cancer therapies are used, then cancer treatment is provided, but specificity for eliminating cancer cells while minimizing harm to healthy tissues is insufficient
Solution Approach 1:
The patent introduces chimeric antigen receptors (CARs) as intermediary molecules that bridge the immune system and cancer cells. These CARs consist of an antigen-binding domain specific to hK2, a hinge region, a transmembrane domain, and intracellular signaling domains. The CAR acts as a mediator that redirects T cells to specifically recognize and attack hK2-expressing cancer cells while sparing healthy tissues that do not express hK2.
Solution Approach 2:
The patent extracts the antigen-binding specificity from traditional antibodies and transfers it to T cell receptors through the CAR construct. By taking out the hK2-specific binding domain and incorporating it into the CAR structure, the system achieves targeted cancer cell elimination without the non-specific effects of traditional therapies.
2Adaptability or versatility
If androgen depletion therapy is used for metastatic prostate cancer, then treatment is provided, but effective treatment options beyond ADT are needed
Solution Approach 1:
The patent changes the fundamental parameter of treatment mechanism by transitioning from hormonal manipulation (ADT) to immune system engagement via CAR-T cells. This parameter change provides a new therapeutic avenue that works through a different biological pathway, offering versatility for patients who have progressed through or are resistant to ADT.
Solution Approach 2:
The patent introduces dynamic adaptability by engineering T cells with CARs that can dynamically recognize and respond to hK2-expressing cancer cells. The immune system's ability to adapt and proliferate provides a dynamic treatment approach that can evolve with the disease, offering improved predictability compared to static hormonal therapies.
3Reliability
If T cell therapy with CAR expression is used, then tumor immunoreactivity is induced, but better cancer therapies utilizing CAR-T cells are still needed
Solution Approach 1:
The patent creates a universal CAR construct design that can be applied to different cancer types expressing hK2, including prostate cancer and potentially other cancers where hK2 is expressed. The modular CAR structure with standardized signaling domains (CD3zeta, CD28, or 4-1BB) provides multi-functionality that enhances both reliability of immunoreactivity and productivity of therapy across different clinical scenarios.
Solution Approach 2:
The CAR construct itself is a composite molecular structure combining elements from different sources: the antigen-binding domain from hK2-specific antibodies, hinge regions from various immunoglobulins, transmembrane domains from T cell receptors, and intracellular signaling domains from costimulatory molecules. This composite design optimizes both the reliability of antigen recognition and the productivity of immune activation.
Data Source
AI summary
The present disclosure provides for chimeric antigen receptors (CARs) that specifically target a human Kallikrein-2 (hK2), and immunoresponsive cells comprising such CARs, for the treatment of cancer.