Engineered Immune Cells with Fc Fusion for Cancer Therapy
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Solution Overview
Problem
Current CAR-T cell immunotherapy faces challenges such as immunosuppression in the tumor microenvironment, tumor heterogeneity, and difficulty in T cell infiltration, which limit its therapeutic effectiveness in cancer treatment.
Innovation Solution
Engineered immune cells are developed, comprising a chimeric antigen receptor with a first antigen binding region, a transmembrane domain, and an intracellular signaling domain, along with an Fc fusion polypeptide with a second antigen binding region and an Fc region, to enhance antigen recognition and immune cell activation, overcoming the limitations of traditional CAR-T cell therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional CAR-T cell therapy is used, then T cell expansion is achieved, but immunosuppression in tumor microenvironment limits therapeutic effectiveness
Solution Approach 1:
The patent combines CAR-T cells with other immune cells (NK cells, macrophages, dendritic cells) into a polyclonal cell therapy system. This merging of different immune cell types with complementary functions overcomes the immunosuppressive environment by introducing cells that can function independently of T cell suppression mechanisms while maintaining antigen-specific targeting capability.
Solution Approach 2:
The invention creates a composite immune cell product containing multiple cell types with different functions - CAR-T cells for antigen recognition, NK cells for cytotoxic activity, macrophages for phagocytosis and antigen presentation, and dendritic cells for immune activation. This composite approach addresses the limitations of single-cell-type CAR-T therapy by distributing functional roles across multiple cell populations.
2Reliability
If traditional CAR-T cell therapy is used, then antigen recognition is achieved, but tumor heterogeneity limits therapeutic effectiveness
Solution Approach 1:
The patent creates a multi-functional immune cell system where different cell types perform different functions: T cells for specific antigen recognition, NK cells for broad cytotoxic activity against tumor cells, macrophages for phagocytosis and antigen presentation, and dendritic cells for immune activation. This multi-functionality allows the therapy to address heterogeneous tumor populations with different antigen expressions and microenvironmental conditions.
Solution Approach 2:
By merging multiple immune cell populations with different recognition and killing mechanisms, the therapy can simultaneously target multiple tumor antigens and overcome tumor heterogeneity. The polyclonal nature of the cell product ensures that at least some cell populations will recognize and eliminate tumor cells expressing various antigen variants.
3Reliability
If traditional CAR-T cell therapy is used, then T cell activation is achieved, but difficulty in T cell infiltration limits therapeutic effectiveness
Solution Approach 1:
The invention combines CAR-T cells with other immune cell types that have different migration and infiltration capabilities. NK cells, macrophages, and dendritic cells can infiltrate tumor sites through different mechanisms than T cells, providing redundant infiltration pathways that overcome the infiltration barriers faced by T cells alone.
4Reliability
If Fc fusion polypeptide is added to engineered immune cells, then immune cell activation is enhanced, but device complexity increases
Solution Approach 1:
The Fc fusion polypeptide acts as an intermediary that bridges the CAR complex and endogenous Fc receptors on immune cells. When the CAR binds antigen, the Fc portion recruits Fc receptor-bearing immune cells (NK cells, macrophages, dendritic cells) to the antigen site, enhancing activation and cytotoxicity without requiring direct genetic modification of all immune cell types.
Data Source
AI summary
The invention relates to an engineered immune cell comprising: (a) a first nucleic acid sequence encoding a chimeric antigen receptor or a chimeric antigen receptor encoded thereby, said chimeric antigen receptor comprises a first antigen binding region, a transmembrane domain, and an intracellular signaling domain; and (b) a second nucleic acid sequence encoding an Fc fusion polypeptide or an Fc fusion polypeptide encoded thereby, said Fc fusion polypeptide comprises a second antigen binding region and an Fc region, wherein the first antigen binding region and the second antigen binding region are not scFv at the same time. The invention also relates to compositions comprising the engineered immune cells of the invention, and the use of the engineered immune cells/compositions in the treatment of cancer.