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Anticorpi anti-HER1
Therapeutic monoclonal antibodies
| Agent | Target | Indication |
|---|---|---|
| TM Erbitux (cetuximab)* | HER1 (EGFR) | Various solid tumours |
| Herceptin (trastuzumab) | HER2 | Metastatic breast cancer |
| MabThera (rituximab) | CD20 | Relapsed/refractory non-Hodgkin’s lymphoma |
| TM Avastin (bevacizumab)* | VEGF | Various solid tumours |
| Crohn’s disease/rheumatoid ® Remicade (infliximab) | TNFα | Arthritis |
| TM Synagis (palivizumab) | Respiratory syncytial virus | Prevention of RSV infection |
| Zenapax (daclizumab) | CD25 (IL-2Rα) | Prevention of acute kidney transplant rejection |
*Agent not licensed
Disease-free survival according to HER1 and TGFa levels in HNSCC
| HER1 | TGFa |
|---|---|
| NED | NED |
| 1.0 | 1.0 Low |
| 0.8 | 0.8 Low surviving |
| 0.6 | 0.6 Medium |
| 0.4 | 0.4 Proportion |
| 0.2 | 0.2 High |
| p=0.0001 | p=0.0001 High |
| 0.0 | 0.0 |
| 0 1 2 3 4 5 6 | 0 1 2 3 4 5 6 Years after surgery |
Grandis R, et al. J Natl Cancer Inst 1998;90:824–32
Development of anti-HER1 MAbs
- Initially proposed by Mendelsohn in 1980s
- Treatment using anti-HER1 MAbs combined with cytotoxic drugs increases antitumour activity in xenograft models
- Development of recombinant humanised and chimeric mouse-human antibodies
- Examples TM– IMC-C225/cetuximab (Erbitux)
Cetuximab: properties
- IgG1 chimerised antibody cetuximab
- Targets HER1, including EGFRvIII
- Binds to HER1 with high affinity (kd 0.1nM)
- Prevents HER1 ligand binding
- Reduces ligand-induced tyrosine kinase (TK) activity
- Stimulates receptor internalisation
Cetuximab: mechanism of action
- Inhibits cell-cycle progression
- Potentiates apoptosis
- Decreases angiogenic growth factor production
- Inhibits metastasis formation
- Enhances the activity of chemo- and radiotherapy
Signal transduction
Cetuximab: synergistic effects with cisplatin on A431 xenografts
| Control | Cetuximab | Cisplatin | Cetuximab + cisplatin |
|---|---|---|---|
| Cetuximab 100 | 6 | ||
| Cisplatin) 3 | 75(cm | ||
| (%) 4 | Survival size 50 | ||
| Tumour 2 | 2500 | ||
| 0 0 5 | 15 25 35 | ||
| 0 20 40 | 60 80 180 Days |
Fan Z, et al. Cancer Res 1993;53:4637–42
Cetuximab: enhanced activity with 5-fluorouracil on pancreatic (BxPC-3) xenografts
| Saline | Cetuximab |
| 1,200 | 5-FU Cetuximab + 5-FU |
| (mm 1,000 volume | 800 600 tumour 400 Mean 200 |
Anteprima
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Dettagli
SSD
Scienze mediche
MED/06 Oncologia medica
I contenuti di questa pagina costituiscono rielaborazioni personali del
Publisher kalamaj di informazioni
apprese con la frequenza delle lezioni
di Oncologia medica e studio autonomo di eventuali libri di riferimento in preparazione
dell'esame finale o della tesi. Non devono intendersi come materiale ufficiale
dell'università Università degli Studi di Foggia o del prof Landriscina Matteo.
Recensioni
7 Ottobre 2016
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