hK2-Binding Antigen Domains and CARs for Thermostable T-Cell Cytotoxicity
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Solution Overview
Problem
Current therapies for prostate and breast cancers, particularly those targeting kallikrein-related peptidase 2 (hK2), lack effective next-generation antigen binding domains for therapeutic and diagnostic purposes, limiting treatment options for patients with hK2-expressing cancers.
Innovation Solution
Development of isolated antigen binding domains, multispecific proteins, chimeric antigen receptors (CARs), and immunoconjugates that specifically bind to hK2, utilizing specific heavy and light chain complementarity determining regions (CDRs) to enhance therapeutic efficacy and diagnostic accuracy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antigen binding domains are used for hK2 targeting, then basic therapeutic function is achieved, but thermostability and anti-tumor efficacy are insufficient
Solution Approach 1:
The patent applies parameter changes by modifying the antigen binding domain structure through specific CDR sequences (HCDR1, HCDR2, HCDR3 of VH and LCDR1, LCDR2, LCDR3 of VL) to achieve improved thermostability. The sequential optimization of CDR regions transforms the original unstable binding domain into a thermostable version capable of withstanding higher temperatures while maintaining hK2 binding affinity.
Solution Approach 2:
The patent creates composite structures by combining multiple CDR regions from different antibody sequences to form an optimized antigen binding domain. This composite approach integrates stabilizing elements from various sources, resulting in a hybrid binding domain that achieves both thermostability and effective hK2 recognition.
2Reliability
If simple antigen binding domains are used, then ease of manufacture is improved, but T-cell mediated cytotoxicity and diagnostic accuracy are limited
Solution Approach 1:
The patent merges the optimized thermostable antigen binding domain with T-cell recruiting domains and cytokine domains to create chimeric antigen receptors (CARs). This combination integrates multiple functional elements—hK2 binding, T-cell recruitment, and immune activation—into a single molecular construct that mediates potent T-cell cytotoxicity against hK2-expressing tumors.
Solution Approach 2:
The patent designs multi-functional CAR structures that simultaneously perform antigen binding, T-cell recruitment, and immune activation. The same antigen binding domain platform is universally applied across different CAR constructs and immunoconjugates, providing a versatile tool for both therapeutic and diagnostic applications against hK2-expressing cancers.
Data Source
AI summary
Embodiments of the present invention provide isolated proteins comprising antigen binding domains that bind kallikrein related peptidase 2 (hK2), including monospecific and bispecific antibodies. Additional embodiments of the invention provide polynucleotides encoding the hk2-specific proteins, vectors, host cells, and methods of making and using them.