Myeloid Cell Conditioning for Cellular Therapy Efficacy
Solution Overview
Problem
Current approaches to cellular immunotherapy often fail to demonstrate efficacy in clinical trials due to unforeseen influences within a patient's system, necessitating pre-treatment or pre-conditioning to make the patient's system receptive to therapeutic cells in the microenvironment.
Innovation Solution
A pharmaceutical composition comprising monocytes with a recombinant polynucleic acid encoding a chimeric fusion protein, including an antigen binding domain and a transmembrane domain, is administered to enhance the therapeutic effectiveness of immune cell inhibitory agents, which can reduce the number or function of immune cells, thereby preparing the microenvironment for cellular therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cellular immunotherapy is administered directly without pre-treatment, then the therapy can be given in its original form, but the patient's immune system may reject or inhibit the therapeutic cells, reducing efficacy
Solution Approach 1:
The patent applies preliminary action by administering immune cell inhibitory agents (such as chemotherapy drugs or immunosuppressants) before cellular immunotherapy to suppress the patient's immune system in advance. This pre-treatment creates a favorable microenvironment that allows therapeutic cells to engraft and function effectively, thereby improving treatment reliability without requiring complex modifications to the therapeutic cells themselves
2Adaptability or versatility
If the patient's immune system is suppressed to accept therapeutic cells, then the microenvironment becomes more receptive, but the overall immune function of the patient is reduced
Solution Approach 1:
The patent applies local quality by using immune cell inhibitory agents that selectively suppress immune function in the tumor microenvironment while preserving systemic immune function. This allows the microenvironment to become receptive to therapeutic cells without completely compromising the patient's overall immune defense, thereby achieving local adaptability without global harm
3Reliability
If high doses of monocytes are administered to ensure therapeutic effectiveness, then the therapy can overcome immune inhibition, but the cost and complexity of cell preparation increases
Solution Approach 1:
The patent applies preliminary action by suppressing the immune system before administering monocytes, which allows lower doses of monocytes to be effective. This approach reduces the burden of cell preparation and manufacturing while still achieving therapeutic effectiveness, as the pre-conditioned microenvironment is more receptive to the therapeutic cells
Data Source
AI summary
Compositions and methods for therapeutic use of engineered myeloid cells are described. Methods for increasing therapeutic effectiveness of immune cells by use of an immune cell inhibitory agent prior to therapy is described. Effective use of myeloid cells in combination therapy is described.