CD28+ T Cell Expansion via Anti-CD3/CD28 Stimulation

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Solution Overview

Problem

Current methods for producing T cells for cancer immunotherapy, such as CAR-T cell therapies, face challenges in enhancing the efficacy and consistency of T-cell expansion, CD8:CD4 ratio, telomere length, and clonal richness, which are critical for effective cancer treatment.

Innovation Solution

The method involves determining the percentage of CD28+ CD8+ T cells in a T-cell population and activating them with anti-CD3 and/or anti-CD28 antibodies, followed by transduction with a viral vector and expansion in the presence of cytokines like IL-7 and IL-15, to achieve improved T-cell product characteristics.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If T cells are expanded using conventional methods (OKT3 antibody, IL-2, and feeder lymphocytes), then T cell numbers increase, but the consistency of T-cell product characteristics (fold expansion, CD8:CD4 ratio, telomere length, clonal richness) remains insufficient

Engineering Contradiction:

ImproveT cell numbersVSAvoidconsistency of T-cell product characteristics

Core Design Contradiction:

Quantity of substanceVSManufacturing precision

Solution Approach 1:

The patent changes the stimulation parameters from conventional OKT3/IL-2 to anti-CD3 and anti-CD28 antibodies, which fundamentally alters the activation pathway and leads to more consistent T-cell product characteristics including fold expansion, CD8:CD4 ratio, telomere length, and clonal richness

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces feeder lymphocytes as an intermediary component in the culture system, which provides necessary co-stimulation and cytokines to enhance the consistency and quality of T-cell expansion while maintaining high cell numbers

Inventive Principle:

Principle #24Intermediary (Mediator)

2Manufacturing precision

If T cells are activated with anti-CD3 and anti-CD28 antibodies, then T-cell product characteristics (fold expansion, CD8:CD4 ratio, telomere length, clonal richness) are improved, but the manufacturing process complexity increases

Engineering Contradiction:

ImproveT-cell product characteristicsVSAvoidmanufacturing process complexity

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent uses a universal culture system that can handle different T-cell inputs and produce consistent high-quality outputs across multiple manufacturing batches, reducing process complexity despite the advanced stimulation methods employed

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Quantity of substance

If the starting T-cell population has low CD28 expression, then the T-cell product shows reduced fold expansion and telomere length, but selecting for high CD28+ cells increases manufacturing selectivity requirements

Engineering Contradiction:

Improvefold expansion and telomere lengthVSAvoidmanufacturing selectivity

Core Design Contradiction:

Quantity of substanceVSAdaptability or versatility

Solution Approach 1:

The patent performs preliminary enrichment of CD28+ T cells before the main expansion process, ensuring that only high-quality precursor cells are subjected to the intensive anti-CD3/anti-CD28 stimulation, which guarantees optimal fold expansion and telomere length outcomes

Inventive Principle:

Principle #10Preliminary action

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

This approach results in T cells with enhanced fold expansion, increased CD8:CD4 ratio, longer telomere length, and higher clonal richness, leading to improved therapeutic efficacy in treating various cancers.

Implementation Method 1

activating them with anti-CD3 and/or anti-CD28 antibodies

Methodology Applied

Scientific EffectAntibody-antigen binding:

Implementation Method 2

activating the determined T cell population with anti-CD3 antibody and/or an anti-CD28 antibody

Methodology Applied

Scientific EffectT cell activation and proliferation:

Implementation Method 3

followed by transduction with a viral vector

Methodology Applied

Scientific EffectViral transduction:

Implementation Method 4

expansion in the presence of cytokines like IL-7 and IL-15

Methodology Applied

Scientific EffectCytokine signaling:

Data Source

PatentUS20250019655A1CD28 t cell cultures, compositions, and methods of using thereof

Publication Date: 2025.01.16 IMMATICS US INC

AI summary

A method for producing T cells with improved efficacy for adoptive immunotherapy includes obtaining a population of CD8+ T cells from a patient or a donor, determining a % of CD28+ CD8+ T cells in the obtained population, activating the determined population with anti-CD3 antibody and anti-CD28 antibody, provided that the determined population comprises at least 50% of CD28+ CD8+ T cells, or activating the determined population with anti-CD3 antibody in the absence of anti-CD28 antibody, provided that the determined population comprises less than 50% of CD28+ CD8+ T cells, transducing the activated population with a viral vector, and expanding the transduced population, in which the transducing and the expanding are carried out in the presence of at least one cytokine.