Allogeneic T Cell Therapy for Chemoresistant EBV-LPD

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Solution Overview

Problem

There is a need for effective treatment methods for Epstein-Barr Virus-associated lymphoproliferative disorders (EBV-LPD) in patients who have failed combination chemotherapy and/or radiation therapy, as these patients often develop aggressive and resistant forms of the disease, posing challenges in achieving successful treatment with desirable safety and efficacy profiles.

Innovation Solution

Administering a population of allogeneic T cells comprising EBV-specific T cells that are restricted by a shared human leukocyte antigen (HLA) allele with the patient's EBV-LPD cells, which have been generated in vitro and sensitized to EBV antigens, providing a targeted immunotherapy approach for patients who have not responded to conventional therapies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If combination chemotherapy and radiation therapy are used to treat EBV-LPD, then initial response is achieved, but the disease becomes aggressive and resistant to treatment

Engineering Contradiction:

Improvetreatment efficacyVSAvoiddisease aggression and resistance

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces allogeneic T cells as an intermediary biological agent between the patient's EBV-LPD and the treatment system. These T cells, which recognize EBV antigens through HLA restriction, serve as a mediator that can target and eliminate resistant tumor cells without the harsh effects of conventional chemotherapy, thereby resolving the contradiction between achieving treatment response and avoiding disease aggression.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the treatment parameter from conventional cytotoxic chemotherapy to targeted cellular immunotherapy. By switching to a different therapeutic modality (T cell-based therapy) with distinct mechanisms of action, the treatment can effectively address chemoresistant and radioresistant EBV-LPD while maintaining better safety profiles, thus resolving the efficacy-resistance contradiction.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If conventional chemotherapy is used to treat EBV-LPD, then disease control is achieved, but safety profile deteriorates in later-line therapy

Engineering Contradiction:

Improvedisease controlVSAvoidtoxicity and safety

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces the mechanical/chemical cytotoxic mechanism of conventional chemotherapy with a biological immunological mechanism. Allogeneic T cells utilize cell-mediated immunity and antigen recognition to destroy EBV-LPD cells, substituting the non-selective chemical damage of chemotherapy with a more precise biological targeting system that maintains disease control while improving safety and reducing toxicity.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent employs allogeneic T cells as a consumable therapeutic agent that can be administered in later-line settings. These T cells, derived from donor sources and matched by HLA alleles, provide effective treatment without the cumulative toxicity associated with repeated chemotherapy cycles, offering a safer alternative for patients who have exhausted conventional therapy options.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Reliability

If HLA-restricted allogeneic T cells are administered to treat EBV-LPD, then targeted immunity is achieved, but treatment complexity increases

Engineering Contradiction:

Improvetargeted immunityVSAvoidtreatment complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent performs preliminary HLA matching between the donor T cells and the patient before treatment administration. By pre-establishing compatibility through HLA allele matching, the system ensures that the allogeneic T cells will be recognized by the patient's immune system as self, reducing rejection risks and simplifying the subsequent treatment process. This preliminary matching action resolves the complexity of ensuring targeted immunity while maintaining treatment feasibility.

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 method effectively treats EBV-LPD resistant to combination chemotherapy and radiation therapy, offering a later-line therapy with low toxicity and demonstrating response in patients who have failed previous treatments, including those with CNS involvement.

Implementation Method 1

administering to the human patient a population of allogeneic T cells comprising EBV-specific T cells; wherein the human patient has failed a combination chemotherapy to treat the EBV-LPD

Methodology Applied

Scientific EffectCell-mediated immunity:

Implementation Method 2

the population of allogeneic T cells is restricted by an human leukocyte antigen (HLA) allele shared with cells of the EBV-LPD

Methodology Applied

Scientific EffectHLA restriction:

Data Source

PatentUS10568908B2Methods of treating Epstein-Barr virus-associated lymphoproliferative disorders by T cell therapy

Publication Date: 2020.02.25 MEMORIAL SLOAN KETTERING CANCER CENT

AI summary

The invention relates to methods of treating an EBV-LPD (Epstein-Barr Virus-associated lymphoproliferative disorder) in a human patient who has failed combination chemotherapy to treat the EBV-LPD and/or radiation therapy to treat the EBV-LPD, comprising administering to the human patient a population of allogeneic T cells comprising EBV-specific T cells.