PRAME Peptide Epitopes for Off-the-Shelf T Cell Therapy

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Solution Overview

Problem

Current methods for generating autologous T cells to target cancer antigens, such as PRAME, are inefficient and unsuitable for urgent cancer therapies due to the time-consuming process of production, particularly for patients undergoing pharmacological or radiation therapies that lead to lymphopenia or immunosuppression.

Innovation Solution

Identification of PRAME-derived peptide epitopes that are recognized by T cells when presented by HLA class 1 or HLA class 2 molecules, along with a method to prime and expand precursor T cells from healthy donors to create a bank of 'off-the-shelf' T cells that can target cancer cells expressing PRAME, enabling rapid deployment for treatment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If autologous T cells are generated to target cancer antigens, then the T cells can specifically recognize and attack cancer cells, but the production process is time-consuming and unsuitable for urgent cancer therapies

Engineering Contradiction:

Improvespecificity of T cell responseVSAvoidproduction time of T cells

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The patent applies preliminary action by pre-identifying and pre-characterizing PRAME peptide epitopes and their HLA restrictions before patient treatment. This allows the T cell therapy to be rapidly deployed 'off-the-shelf' without time-consuming in-vitro generation for each patient, while still maintaining specific anti-cancer activity through the pre-defined epitope targeting

Inventive Principle:

Principle #10Preliminary action

2Adaptability or versatility

If autologous T cells are generated for cancer treatment, then the T cells can be tailored to the patient's cancer, but the process becomes complex and resource-intensive

Engineering Contradiction:

Improvepatient-specific customizationVSAvoidcomplexity of T cell production process

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent applies universality by identifying PRAME epitopes that are restricted by common HLA alleles (such as HLA-A*02:01, HLA-B*35:03, HLA-B*44:03) that are prevalent in the population. This creates a universal T cell therapy platform that can be applied to multiple patients with different HLA types, reducing the need for fully custom-generated autologous T cells for each patient while maintaining therapeutic relevance

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Reliability

If T cells are generated from patients undergoing pharmacological or radiation therapy, then the T cells can target the patient's cancer, but the patient's lymphopenia or immunosuppression reduces the availability of suitable T cells

Engineering Contradiction:

Improveanti-tumor activity of T cellsVSAvoidnumber of available T cells

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The patent applies the intermediary principle by using healthy donor T cells as an alternative source instead of relying on the patient's own T cells. The healthy donors serve as intermediaries who provide the necessary T cell population, which is then HLA-matched and activated to target the patient's cancer. This bypasses the problem of lymphopenia and immunosuppression in cancer patients while maintaining the ability to generate anti-tumor responses

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20230190902A1Identification of HLA-restricted prame peptide epitopes, prame-specific t cells suitable for "off-the-shelf" treatment of cancer expressing prame

Publication Date: 2023.06.22 CHILDRENS NAT MEDICAL CENT

AI summary

The invention pertains to a method for treating a cancer which expresses PRAME using T cells which recognize specific peptide epitopes of PRAME, to a method for producing T cells that target cancer cells expressing PRAME, the peptide epitopes of PRAME themselves and to compositions and methods of treatment using these peptides.