Novel PD-1 Binding Domains for Enhanced Cancer Therapy
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Solution Overview
Problem
Current cancer treatments, particularly those targeting PD-1, often face challenges in achieving complete remission due to limited efficacy and toxicity, necessitating the development of novel PD-1 binding domains with higher affinity and potency for therapeutic antibodies.
Innovation Solution
The development of novel anti-human PD-1 binding domains with enhanced binding affinity and potency, comprising specific heavy and light chain variable regions, which can be incorporated into monospecific or multispecific antibodies to effectively block PD-1 ligand binding, thereby activating the immune system to target cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional PD-1 targeting antibodies are used, then cancer treatment is achieved, but binding affinity and potency are insufficient leading to limited efficacy
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequences of the binding domain through systematic mutations and selections. Specific substitutions in the CDR regions (e.g., HCDR1, HCDR2, HCDR3) are made to optimize binding affinity to PD-1, transforming the molecular parameters of the antibody to achieve superior therapeutic efficacy compared to conventional antibodies
2Reliability
If conventional PD-1 antibodies are used, then immune system activation occurs, but potency is insufficient requiring higher doses with increased toxicity
Solution Approach 1:
The patent modifies molecular parameters of the binding domain to achieve higher potency at lower concentrations. By optimizing amino acid sequences and improving binding kinetics, the antibody can activate the immune system effectively at reduced doses, thereby minimizing toxic side effects associated with high-dose conventional therapies
Data Source
AI summary
The present disclosure relates to novel PD-1 binding domains that have a higher binding affinity for human PD-1 than a reference PD-1 binding domain. The PD-1 binding domains of the present disclosure further provide a comparable, or equal or higher, potency in blocking ligand binding to human PD-1 than a reference PD-1 antibody. The present disclosure further relates to binding moieties comprising such PD-1 binding domains. Also provided is a method for treating a disease, in particular a disease associated with a suppressed immune system, such as cancer, with a PD-1 binding domain or binding moiety of the present disclosure. The present disclosure further relates to nucleic acids encoding the heavy chain variable region of the PD-1 binding domains, and a vector and cell comprising such nucleic acid.