Donor KIR3DL1 and HLA-B Typing for Leukemia Control

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Solution Overview

Problem

Current hematopoietic stem cell transplantation methods face challenges in controlling leukemia relapse and mortality due to inadequate donor selection, particularly in allogeneic HCT, where differences in KIR3DL1 and HLA-B alleles influence NK cell inhibition and tumor control.

Innovation Solution

Selecting donors based on typing KIR3DL1 and HLA-B alleles to identify combinations that minimize NK cell inhibition, thereby maximizing leukemic toxicity and improving survival outcomes by choosing donors with low inhibitory KIR3DL1 and HLA-Bw4 allele combinations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If donors with high inhibitory KIR3DL1 and HLA-Bw4 allele combinations are selected, then NK cell inhibition is strong, but leukemia control is reduced and relapse rate increases

Engineering Contradiction:

Improveleukemia controlVSAvoidNK cell inhibition

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by selecting donors with specific KIR3DL1 expression levels (low vs high) and specific HLA-Bw4 subtypes (I80 vs T80) to optimize the inhibitory interaction strength. This genetic parameter selection directly controls the degree of NK cell inhibition, thereby improving leukemia control while maintaining acceptable graft-versus-host disease risk

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent inverts the conventional approach by selecting for weaker rather than stronger NK cell inhibition. Instead of maximizing inhibitory interactions between donor KIR3DL1 and recipient HLA-Bw4, the patent deliberately chooses donor-recipient combinations with reduced inhibition (low KIR3DL1 expression or mismatched HLA-Bw4 subtypes), thereby enhancing anti-leukemia activity

Inventive Principle:

Principle #13The other way round (Inversion)

2Reliability

If donor selection is based only on HLA matching, then transplantation process is simple, but leukemia relapse control is insufficient

Engineering Contradiction:

Improveleukemia relapse controlVSAvoiddonor selection process

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the donor selection process into multiple independent evaluation stages: first HLA matching, then KIR3DL1 allele typing, followed by HLA-Bw4 subtype analysis, and finally integration of all parameters to select the optimal donor combination. This segmented approach systematically improves leukemia control while maintaining procedural clarity

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent applies preliminary action by performing KIR3DL1 and HLA-Bw4 typing on potential donors before final selection, allowing prediction of NK cell inhibitory interactions in advance. This preliminary genetic characterization enables informed donor selection that optimizes both leukemia control and graft-versus-host disease risk before transplantation proceeds

Inventive Principle:

Principle #10Preliminary action

Data Source

PatentUS10407727B2Donor <i>KIR3DL1 </i>and <i>HLA-B </i>subtypes and leukemia control in HLA-compatible allogenic hematopoietic stem cell transplantation

Publication Date: 2019.09.10 MEMORIAL SLOAN KETTERING CANCER CENT

AI summary

This disclosure generally relates to donor selection for hematopoietic stem cell transplantation. In particular, this disclosure relates to typing KIR3DL1 and HLA-B alleles as basis for donor selection.