Natural Killer (NK)- and T-Cell Engaging Antibody-Derived Therapeutics
Abstract
:1. Introduction
1.1. Frequently Used Trigger Molecules and Classes of Effector Cells
Effector cells | Trigger molecules |
---|---|
T-cells | CD3, TCRα,β, CTLA4, PD1, CD28 |
NK-cells | CD16a, NKG2D, NKp30, NKp40, LFA1 |
Monocytes | CD89, CD64, CD32a, CD16a |
Macrophages | CD89, CD64, CD32a, CD16a |
Neutrophilic Granulocytes | CD89, CD64, CD32a |
1.2. Examples of ab-Derived Agents Recruiting Effector Cells Other than NK- and T-Cells
Specificity | Format | Disease | Development status | Company | Trial |
---|---|---|---|---|---|
CD19, CD3 | BsscFv | NHL, B-ALL | Phase I/II | Amgen | NCT01207388, NCT00274742 |
EpCAM, CD3 | BsscFv | Various tumors | Phase I | Amgen | NCT00635596. |
CEA, CD3 | BsscFv | Gastrointestinal cancers | Phase I | Amgen | NCT01284231. |
EpCAM, CD3 | Hybrid IgG | Ovarian and gastric cancer, malignant ascites | Phase II/market approval | Trion | NCT00464893 |
HER2/neu, CD3 | Hybrid IgG | Breast cancer | Phase II | Trion | NCT00522457 |
CD20, CD3 | Hybrid IgG | B-cell lymphoma | Phase I/II | Trion | NCT01138579 |
CD30, CD16a | TandAb | Hodgkin lymphoma | Phase I/IIa | Affimed | NCT01221571 |
2. Redirecting NK- and T-Cells for Cancer Therapy
2.1. T-Cells as Effectors for Cancer Therapy
2.1.1. Optimization of T-Cell Activity
2.1.2. Recruiting T-Cells via CD3
Cell type | Leukocytes per µl blood |
---|---|
T-cells | 300–900 |
NK-cells | 120–350 |
Monocytes | 200–600 |
Macrophages | - |
Granulocytes | 1800–7000 |
2.2. NK-Cells for Cancer Therapy
2.2.1. Recruitment of NK-Cells by Anti-tumor Abs
2.2.2. NK-Cell Recruiting ab-Derivates
2.2.3. Immunoligands for the Recruitment of NK-Cells
3. Conclusions
Acknowledgments
References and Notes
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Stein, C.; Schubert, I.; Fey, G.H. Natural Killer (NK)- and T-Cell Engaging Antibody-Derived Therapeutics. Antibodies 2012, 1, 88-123. https://doi.org/10.3390/antib1010088
Stein C, Schubert I, Fey GH. Natural Killer (NK)- and T-Cell Engaging Antibody-Derived Therapeutics. Antibodies. 2012; 1(1):88-123. https://doi.org/10.3390/antib1010088
Chicago/Turabian StyleStein, Christoph, Ingo Schubert, and Georg H. Fey. 2012. "Natural Killer (NK)- and T-Cell Engaging Antibody-Derived Therapeutics" Antibodies 1, no. 1: 88-123. https://doi.org/10.3390/antib1010088