Immunocytokines
Abstract
:1. Introduction
2. Molecular Formats
2.1. Targeting Properties of Antibody Formats
2.2. Targeting Properties of Immunocytokines
3. Targets
Antigen | Expression profile | Antibody |
---|---|---|
Disease cell surface | ||
EpCAM Epithelial cell adhesion molecule | Physiologically expressed in epithelia Over-expressed in breast, colorectal and pancreatic carcinomas. | KS |
GD2 Disialoganglioside | Physiological expression restricted to cerebellum and peripheral nerves. Expressed in neuroectodermal tumors including melanoma, neuroblastoma. | Ch14.18 |
Disease environment | ||
EDA / EDB of fibronectin Extra-domains EDA and EDB of fibronectin | Physiological expression restricted to endometrium in the proliferating phase. Expressed around the neo-vasculature and in the stroma of aggressive tumours and in chronic inflammation. | F8 / L19 and BC1 |
A1 domain of Tenascin-C | Physiological expression restricted to endometrium in the proliferating phase. Expressed around the neo-vasculature and in the stroma of aggressive tumours and in chronic inflammation. | F16 |
DNA / Histone complexes | Normally not accessible. Exposed in necrotic tissue. | NHS |
3.1. Targeting the Cell Surface
3.2. Targeting the Disease Environment
3.3. Target Identification
4. Fusion Partners
4.1. Cytokines in Cancer
Compound | Antibody format | Target antigen | Indications | Clinical phase | Company |
---|---|---|---|---|---|
Pro-inflammatory | |||||
F16-IL2 | Diabody | A1 domain of tenascin-C | Breast cancer and lung cancer | Phase II | Philogen |
L19-IL2 | Diabody | EDB of fibronectin | Melanoma | Phase II | Philogen |
hu14.18-IL2 | IgG | GD2 | Melanoma and neuroblastoma | Phase I/II | Merck KGaA |
KS-IL2 | IgG | EpCAM | Ovarian cancer, colorectal cancer, prostate cancer and NSCL carcinoma | Phase I | Merck KGaA |
NHS-IL2LT | IgG | DNA/ histone | Non-Hodgkin lymphoma and NSCL carcinoma | Phase I | Merck KGaA |
NHS-IL12 | IgG | DNA/ histone | Epithelial and mesenchymal malignant tumors | Phase I | Merck KGaA |
BC1-IL12 | IgG | EDB of fibronectin | Melanoma | Phase I/II | Antisoma |
L19-TNF | Trimeric scFv | EDB of fibronectin | Melanoma (isolated limb perfusion) | Phase I/II | Philogen |
Anti-inflammatory | |||||
F8-IL10 | Diabody | EDA of fibronectin | Rheumatoid arthritis | Phase I | Philogen |
4.1.1. IL2-Based Immunocytokines
4.1.2. IL12- and TNF-Based Immunocytokines
4.2. Cytokines in Chronic Inflammatory Diseases
4.2.1. IL10 Immunocytokines
5. Combination Studies
5.1. Selected Preclinical Combination Therapies
5.2. Combination Therapies in Clinical Development
6. Concluding Remarks
Acknowledgments
Conflict of Interest
References
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Gutbrodt, K.L.; Neri, D. Immunocytokines. Antibodies 2012, 1, 70-87. https://doi.org/10.3390/antib1010070
Gutbrodt KL, Neri D. Immunocytokines. Antibodies. 2012; 1(1):70-87. https://doi.org/10.3390/antib1010070
Chicago/Turabian StyleGutbrodt, Katrin L., and Dario Neri. 2012. "Immunocytokines" Antibodies 1, no. 1: 70-87. https://doi.org/10.3390/antib1010070