NK and Gamma Delta T Cell Composition for Allogeneic Immunotherapy
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current immunotherapy approaches, such as CAR-T cell therapies, face challenges including MHC restriction, severe side effects, poor migration to solid tumors, and complex, costly manufacturing processes, limiting their widespread application and efficacy.
Innovation Solution
A composition comprising Natural Killer (NK) cells and γδ T cells, with at least 40% of γδ T cells being CD56bright or expressing CD56, expanded using an anti-TCR delta variable 1 antibody and Interleukin-15, in the absence of Interleukin-4, to create a therapeutically effective cell population for cancer, infectious, and inflammatory diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR-modified αβ T-cell therapies are used, then therapeutic efficacy is improved, but MHC restriction causes fatal graft versus host disease in allogenic setting
Solution Approach 1:
The patent segments the T-cell population into different subsets (αβ T cells, γδ T cells, NK cells) and selectively expands γδ T cells and NK cells that do not cause graft versus host disease, while removing or suppressing αβ T cells through depletion steps in the manufacturing process
Solution Approach 2:
The patent extracts and removes harmful αβ T cells from the cell therapy product through specific depletion methods, isolating only the beneficial γδ T cells and NK cells that provide therapeutic efficacy without causing graft versus host disease
2Reliability
If CAR-T therapies are administered, then tumor targeting is achieved, but unwanted side effects such as cytokine release syndrome and neurotoxicity occur
Solution Approach 1:
The patent uses short-term in vitro expansion of γδ T cells and NK cells with controlled cytokine exposure, allowing the cells to be activated and expanded temporarily to achieve therapeutic numbers, then administered without the persistent harmful effects seen with CAR-T therapies
Solution Approach 2:
The patent changes the cytokine parameters during manufacturing by using specific cytokine combinations and durations that activate γδ T cells and NK cells without triggering excessive cytokine release, thereby achieving tumor targeting without severe side effects
3Reliability
If αβ T cells are used for therapy, then immune response is activated, but poor migration to solid tumour sites hinders therapeutic efficacy
Solution Approach 1:
The patent uses γδ T cells and NK cells as alternative copies of immune effectors that share the ability to activate immune responses but possess superior migratory properties to solid tumors, effectively copying the beneficial immune activation function while improving tumor targeting speed
4Productivity
If complex manufacturing processes with multiple cytokines and feeder cells are used, then cell expansion is achieved, but manufacturing complexity and cost increase
Solution Approach 1:
The patent extracts and removes the need for complex feeder cell systems and multiple cytokine combinations by using a simplified manufacturing process that relies on selective anti-Vδ1 antibody coating and limited cytokine supplementation to achieve robust γδ T cell and NK cell expansion
Solution Approach 2:
The patent changes the manufacturing parameters by using a defined medium with controlled cytokine supplementation and anti-Vδ1 antibody coating, replacing the complex undefined conditions with feeder cells and multiple cytokines, thereby simplifying the manufacturing process while maintaining high cell expansion
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 composition enhances cytotoxicity and immune response, overcoming MHC restrictions and manufacturing complexities, providing a scalable and effective allogenic cellular therapy with improved safety and efficacy.
Implementation Method 1
contacting a sample with an anti-TCR delta variable 1 (anti-Vδ1) antibody
Implementation Method 2
in the presence of Interleukin-15 (IL-15) and in the absence of Interleukin-4 (IL-4) and culturing the mixed cell population
Implementation Method 3
Vδ1 cells also use an MHC unrestricted TCR to recognise tumour associated antigens
Implementation Method 4
their potential to cooperate with antibodies to execute antibody mediated cellular cytotoxicity (ADCC)
Data Source
AI summary
The invention relates to compositions comprising NaturalKiller (NK) cells and γδ T cells, particularly for use in adoptive immunotherapy. The invention also provides method for preparing such compositions which comprises contacting a sample with an anti-TCR delta variable 1 (anti-Vδ1) antibody.