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Immune response manipulation: recombinant immunoreceptors endow T-cells with predefined specificity
Hinrich Abken1, Andreas Hombach, Claudia Heuser
1Lab. Tumorgenetik, Klinik I für Innere Medizin and Zentrum für Molekulare Medizin Köln (ZMMK), Universität zu Köln, D-50924 Köln, Germany. hinrich.abken@medizin.uni-koeln.de
Current Pharmaceutical Design
|July 23, 2003
Summary
Immunotherapy harnesses T-cells to fight cancer by engineering them with novel receptors. This "T-body" strategy enables T-cells to target tumor cells independently of major histocompatibility complex (MHC) recognition, offering a promising approach for cancer treatment.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Immunotherapy is gaining traction for treating malignant diseases.
- T-cell immunity is crucial for controlling tumor growth.
- Current strategies aim to activate T-cells against tumor cells, bypassing major histocompatibility complex (MHC)-restricted antigen recognition.
Purpose of the Study:
- To review the immunoreceptor ("T-body") strategy for redirecting T-cell functions.
- To explore the potential of adoptive immunotherapy for malignant diseases using this approach.
Main Methods:
- Grafting cytolytic T-cells with antigen-specific, recombinant receptors (immunoreceptors).
- Designing receptors with an extracellular single-chain antibody fragment (scFv) targeting tumor-associated antigens.
- Incorporating intracellular signaling domains (e.g., Fc epsilon RI gamma-chain or CD3 zeta-chain) for T-cell activation.
Main Results:
- The immunoreceptor strategy enables MHC-independent binding of antibodies to antigens.
- This approach facilitates efficient T-cell activation against target cells.
- Engineered T-cells can be directed against any cell expressing a specific antigen, including tumor and virally infected cells.
Conclusions:
- The immunoreceptor strategy offers a versatile method for adoptive immunotherapy.
- It holds potential for treating malignant diseases by redirecting T-cell specificity.
- Further discussion on limitations and future perspectives of this strategy is warranted.