Table 1.
Therapeutic Monoclonal Antibodies to Overcome Immune Escape in HNSCC
| Drug (Company) | Target | IgG subclass | Phase of development, human cancer | HNSCC development |
|---|---|---|---|---|
| Tumor Antigen Targeted Monoclonal Antibodies | ||||
| Cetuximab (Bristol-Myers Squibb, Eli Lilly) | EGFR antagonist | IgG1 | III/IV (FDA-approved HNSCC, NSCLC, colon cancer) | Phase III/IV |
| Panitumumab (Amgen) | EGFR antagonist | IgG2 | III/IV (FDA-approved colon cancer) | Phase II/III |
| Onartuzumab (Genentech) | cMet antagonist (single-arm Fab) | IgG1 | II/III | --- |
| Pertuzumab (Genentech) | HER2 antagonist | IgG1 | III | --- |
| AV-203 (Aveo) | HER3 antagonist | IgG1 | I | Phase I (monotherapy; cetuximab combination) |
| MM-121 (Merck) | HER3 antagonist | IgG2 | I/II | --- |
| RO5479599 (Roche) | HER3 antagonist | Glyco-engineered | I/II | --- |
| Cixutumumab (Eli Lilly) | IGFR antagonist | IgG1 | II | Phase 0-II (neoadjuvant monotherapy; cetuximab combination) |
| Cytokine Targeted Monoclonal Antibodies | ||||
| Bevacizumab (Genentech) | VEGF neutralizer | IgG1 | III/IV (FDA approved in NSCLC, colon) | Phase III (platinum chemotherapy +/−) |
| Ficlatuzumab (Aveo) | HGF neutralizer | IgG1 | I/II | Phase I (cetuximab combination; cisplatin-radiation combination) |
| AMG 102 (Amgen) | HGF neutralizer | IgG2 | I/II | --- |
| Fresolimumab (Genzyme) | TGF-β neutralizer | IgG4 | --- | |
| Siltuximab (Janssen Biotech) | IL-6 neutralizer | IgG1 | I/II | --- |
| TNF Receptor Targeted Monoclonal Antibodies | ||||
| CP-870,893 (Pfizer) | CD40 agonist | IgG2 | I | --- |
| OX40 mAb (AgonOx, Providence Health) | OX40 agonist | IgG2 | I | --- |
| Urelumab (Bristol-Myers Squibb) | CD137 agonist | IgG4 | I | --- |
| PF-05082566 (Pfizer) | CD137 agonist | IgG2 | I | --- |
| Immune Checkpoint Targeted Monoclonal Antibodies | ||||
| Ipilimumab (Bristol-Myers Squibb) | CTLA4 | IgG1 | III/IV (FDA approved in melanoma | Phase I (cetuximab-radiation combination) |
| Tremelimumab (Pfizer) | CTLA4 | IgG2 | III | --- |
| Nivolumab (Bristol-Myers Squibb) | PD-1 | IgG4 | I/II/III | --- |
| Lambrolizumab (Merck) | PD-1 | IgG4 | I/II | --- |
| BMS-936559 (Bristol-Myers Squibb) | PD-L1 | IgG4 | I | --- |