Humanized CAR T Cells for Targeted Cancer Therapy

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Solution Overview

Problem

Current cancer therapies using CARs and BiTEs face challenges such as immune responses from non-human antigen recognition domains and systemic toxicity, necessitating the development of compositions and methods for targeted delivery of human or humanized CARs and bispecific antibodies.

Innovation Solution

Genetically modified T cells expressing chimeric antigen receptors (CARs) with antigen binding domains derived from human or humanized antibodies, combined with bispecific antibodies, are administered to stimulate a targeted immune response, reducing toxicity and immune reactions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If non-human extracellular antigen recognition domain is used in CAR, then CAR can recognize and lyse tumor cells, but it can trigger HAMA response causing allergic reactions and reducing therapeutic safety

Engineering Contradiction:

Improvetumor recognition and lysis capabilityVSAvoidHAMA response and allergic reactions

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the species origin parameter of the antigen recognition domain from non-human (mouse) to human or humanized, thereby maintaining tumor recognition capability while eliminating the HAMA response that causes allergic reactions

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent converts the harmful immune response (HAMA) into a beneficial outcome by using humanized antibodies that are specifically designed to avoid triggering human immune rejection, thereby turning a potentially harmful foreign protein into a safe therapeutic agent

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

2Reliability

If BiTE is delivered systemically, then it can induce directed lysis of target tumor cells, but it results in toxicity

Engineering Contradiction:

Improvetumor cell lysis efficacyVSAvoidsystemic toxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses CAR-T cells as intermediary carriers that selectively deliver the bispecific antibody to tumor sites through antigen-directed trafficking, thereby maintaining tumor cell lysis efficacy while avoiding systemic toxicity through localized delivery

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The CAR-T cells autonomously navigate to tumor sites using their antigen recognition capability, enabling self-directed delivery of the bispecific antibody without requiring systemic administration, thus achieving localized therapeutic effect with minimal systemic exposure

Inventive Principle:

Principle #25Self-service

Data Source

PatentUS20240018271A1Enhancing Activity of CAR T Cells by Co-Introducing a Bispecific Antibody

Publication Date: 2024.01.18 THE TRUSTEES OF THE UNIV OF PENNSYLVANIA

AI summary

The present invention provides compositions and methods for treating cancer in a human. The invention includes administering a T cell, genetically modified to express a chimeric antigen receptor (CAR), a bispecific antibody, or a combination thereof to a subject. The CAR and bispecific antibody of the invention can comprise a human antibody, a humanized antibody, or antigen-binding fragments thereof.