Table 2. Anticancer immunotherapeutics currently approved by regulatory agencies worldwide.
| Paradigm | Agent | Indication(s) | Year* | Proposed mechanism of action |
|---|---|---|---|---|
| Dendritic cell-based immunotherapies | Sipuleucel-T | Prostate carcinoma | 2010 | Priming of a PAP-specific immune response |
| Immunogenic cell death inducers | Bleomycin | Multiple hematological and solid tumors |
<1995 | DNA-damaging agent |
| Bortezomib | Mantle cell lymphoma Multiple myeloma |
2003 | Proteasomal inhibitor | |
| Cyclophosphamide | Multiple hematological and solid tumors |
<1995 | Alkylating agent | |
| Doxorubicin | Multiple hematological and solid tumors |
<1995 | DNA-intercalating agent | |
| Epirubicin | Breast carcinoma | 1999 | DNA-intercalating agent | |
| Mitoxantrone | Acute myeloid leukemia Prostate carcinoma |
<1995 | DNA-intercalating agent | |
| Oxaliplatin | Colorectal carcinoma | 2002 | DNA-damaging agent | |
| Photodynamic therapy | Multiple hematological and solid tumors |
1996 | Induction of oxidative stress with damage to (intra)cellular membranes | |
| Radiation therapy | Multiple hematological and solid tumors |
<1995 | DNA-damaging agent and oxidative stress inducer | |
| Immunostimulatory cytokines | IL-2 | Melanoma Renal cell carcinoma |
<1995 | Non-specific immunostimulation |
| IFN-α2a | Chronic myeloid leukemia Hairy cell leukemia Melanoma |
1999 | Non-specific immunostimulation | |
| IFN-α2b | Multiple hematological and solid tumors |
<1995 | Non-specific immunostimulation | |
| Immunomodulatory mAbs | Ipilimumab | Melanoma | 2011 | Blockage of CTLA4-dependent immunological checkpoints |
| Nivolumab | Melanoma | 2014 | Blockage of PDCD1-dependent immunological checkpoints | |
| Pembrolizumab | Melanoma | 2014 | Blockage of PDCD1-dependent immunological checkpoints | |
| Oncolytic viruses | Oncorine H101 | Head and neck cancer | 2005 | Selective lysis of malignant cells |
| Peptide-based vaccines | Vitespen | Renal cell carcinoma | 2008 | Activation of a tumor-specific immune response |
| PRR agonists | Bacillus Calmette-Guérin | Non-invasive bladder transitional cell carcinoma |
<1995 | TLR2/TLR4 agonist |
| Imiquimod | Actinic keratosis Condylomata acuminata Superficial basal cell carcinoma |
1997 | TLR7 agonist | |
| Mifamurtide | Osteosarcoma | 2009 | NOD2 agonist | |
| Monophosphoryl lipid A | Prevention of HPV-associated cervical carcinoma | 2009 | TLR2/TLR4 agonist | |
| Picibanil | Gastric carcinoma Head and neck cancer Lung carcinoma Thyroid carcinoma |
<1995 | TLR2/TLR4 agonist | |
| Tumor-targeting mAbs | Alemtuzumab | Chronic lymphocytic leukemia | 2001 | Selective recognition/opsonization of CD52+ neoplastic cells |
| Bevacizumab | Colorectal carcinoma Glioblastoma multiforme Cervical carcinoma Lung carcinoma Renal cell carcinoma |
2004 | VEGFA neutralization | |
| Brentuximab vedotin | Anaplastic large cell lymphoma Hodgkin's lymphoma |
2011 | Selective delivery of MMAE to CD30+ neoplastic cells | |
| Blinatumumab | Acute lymphoblastic leukemia | 2014 | CD3- and CD19-specific BiTE | |
| Catumaxomab | Malignant ascites in patients with EPCAM+ cancer |
2009 | CD3- and EPCAM-specific BiTE | |
| Cetuximab | Head and neck cancer Colorectal carcinoma |
2004 | Inhibition of EGFR signaling | |
| Denosumab | Breast carcinoma Prostate carcinoma Bone giant cell tumors |
2011 | Inhibition of RANKL signaling | |
| Gemtuzumab ozogamicin | Acute myeloid leukemia | 2000 | Selective delivery of calicheamicin to CD33+ neoplastic cells | |
| Ibritumomab tiuxetan | Non-Hodgkin lymphoma | 2002 | Selective delivery of 90Y or 111In to CD20+ neoplastic cells | |
| Panitumumab | Colorectal carcinoma | 2006 | Inhibition of EGFR signaling | |
| Pertuzumab | Breast carcinoma | 2012 | Inhibition of HER2 signaling | |
| Obinutuzumab | Chronic lymphocytic leukemia | 2013 | Selective recognition/opsonization of CD20+ neoplastic cells | |
| Ofatumumab | Chronic lymphocytic leukemia | 2009 | Selective recognition/opsonization of CD20+ neoplastic cells | |
| Ramucirumab | Gastric or gastroesophageal junction adenocarcinoma |
2014 | Inhibition of KDR signaling | |
| Rituximab | Chronic lymphocytic leukemia Non-Hodgkin lymphoma |
1997 | Selective recognition/opsonization of CD20+ neoplastic cells | |
| Siltuximab | Multicentric Castleman's disease | 2014 | IL-6 neutralization | |
| Tositumomab | Non-Hodgkin lymphoma | 2003 | Selective recognition/opsonization of, or selective delivery of 90Y or 111In to, CD20+ neoplastic cells | |
| Trastuzumab | Breast carcinoma Gastric or gastroesophageal junction adenocarcinoma |
1998 | Selective recognition/opsonization of, or selective delivery of mertansine to, HER2+ cancer cells | |
| Others | Lenalidomide | Mantle cell lymphoma Myelodysplastic syndrome Multiple myeloma |
2005 | IKZF degradation and immunomodulation |
| Pomalidomide | Multiple myeloma | 2013 | IKZF degradation and immunomodulation | |
| Thalidomide | Multiple myeloma | 2006 | IKZF degradation and immunomodulation | |
| Trabectedin | Soft tissue sarcoma Ovarian carcinoma |
2007 | Reprogramming of tumor-associated macrophages |
Abbreviations: ACPP, acid phosphatase, prostate; BiTE, Bispecific T-cell engager; CTLA4, cytotoxic T lymphocyte-associated protein 4; EGFR, epidermal growth factor receptor; EPCAM, epithelial cell adhesion molecule; HPV, human papillomavirus; IL, interleukin; IKZF, IKAROS family zinc finger; KDR, kinase insert domain receptor; mAb, monoclonal antibody; MMAE, monomethyl auristatin E; NOD2, nucleotide-binding oligomerization domain containing 2; PDCD1, programmed cell death 1; PRR, pattern recognition receptor; RANKL, Receptor activator of NF-κB ligand; TLR, Toll-like receptor; VEGFA, vascular endothelial growth factor A.
*
year of first approval.