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Table 2 A representative panel of therapeutic agents that target specific compartments of TME, an occult culprit hiding in the backdrop of pathologies

From: New horizons in tumor microenvironment biology: challenges and opportunities

Molecule Target Molecular type Company Status
ECM/fibroblasts
Sonidegib SMO Small molecule Novartis Phase II (NCT01708174, NCT01757327, NCT02195973)
Vasculature
Bevacizumab VEGFA Antibody Genentech/Roche FDA-approved ((BLA) 125085)
Vandetanib VEGFRs, PDGFRs, EGFR Small molecule AstraZeneca FDA-approved ((NDA) 022405)
Sunitinib VEGFRs, PDGFRs, FLT3, CSF1R Small molecule Pfizer FDA-approved ((NDA) 021938)
Axitinib VEGFRs, PDGFRs, KIT Small molecule Pfizer FDA-approved ((NDA) 022324)
Sorafenib VEGFRs, RAF PDGFRs, KIT Small molecule Bayer FDA-approved ((NDA) 021923)
Pazopanib VEGFRs, PDGFRs, KIT Small molecule GlaxoSmithKline FDA-approved ((NDA) 022465)
Cabozantinib VEGFR2, RETMET Small molecule Exelixis FDA-approved ((NDA) 023756)
Ziv-aflibercept VEGFA, VEGFB, PIGF Receptor-Fc fusion Regeneron FDA-approved ((BLA) 125418)
AMG-386 ANG2 RP-Fc fusion protein Amgen Phase III (NCT01204749, NCT01493505, NCT01281254)
Parsatuzumab EGFL-7 Antibody Genentech/Roche Phase II (NCT01399684, NCT01366131)
Enoticumab DLL4 Antibody Regeneron Phase I (NCT00871559)
Demcizumab DLL4 Antibody OncoMed Phase I (NCT00744562, NCT01189968, NCT01189942, NCT01189929)
Nesvacumab ANG2 Antibody Regeneron Phase I (NCT01688960, NCT01271972)
Immune
Ipilimumab CTLA-4 Antibody Bristol-Myers Squibb FDA-approved ((BLA) 125377)
Sipuleucel-T PAP DC vaccine Dendreon FDA-approved ((BLA) 125197)
Aldesleukin IL-2 RP Prometheus FDA-approved ((BLA) 103293)
IFN-α-2b IFN-α receptor RP Merck FDA-approved ((BLA) 103132)
MK-3475 PD1 Antibody Merck Phase III (NCT01866319)
Nivolumab PD1 Antibody Bristol-Myers Squibb Phase III (NCT01642004, NCT01668784, NCT01673867, NCT01721746, NCT01721772, NCT01844505)
Nivolumab OX40 Antibody Bristol-Myers Squibb and PPMC Phase III (NCT01642004, NCT01668784, NCT01673867, NCT01721746, NCT01721772, NCT01844505)
MPDL-3280A PDL1 Antibody Genentech/Roche Phase II (NCT01846416)
PLX-3397 KIT, CSF1R, FLT3 Small molecule Plexxikon Phase II (NCT01349036)
BMS-663513 CD137 (4-1BB) Antibody Bristol-Myers Squibb Phase II (NCT00612664)
Blinatumomab CD3 and CD19 Bi-specific scFv Amgen Phase II (NCT01741792, NCT01466179, NCT01207388, NCT01471782, NCT00560794, NCT01209286)
AMG-820 CSF1R Antibody Amgen Phase I (NCT01444404)
AMP-224 PD1 Antibody GlaxoSmithKline Phase I (NCT01352884)
TRX-518 GITR Antibody GITR, Inc. Phase I (NCT01239134)
IMC-CS4 CSR1R Antibody ImClone/Eli Lilly Phase I (NCT01346358)
CP-870,893 CD40 Antibody Pfizer Phase I (NCT00711191, NCT01008527, NCT00607048, NCT01456585, NCT01103635)
  1. References listed in the status column pertain to the molecule as a TME-modifying agent, either the FDA application, where approved, or the national clinical trial identification of the oncology trial in the latest phase is listed (note that in some cases the drug may also be tested or approved for an indication for which it acts directly on the tumor cell compartment, which will not be referenced here). ANG2, Angiopoietin 2; BLA, Biological license application; CD40, Cluster of differentiation antigen 40; CD137, Cluster of differentiation antigen 137; CSF1R, Colony stimulating factor 1 receptor; CTLA-4, Cytotoxic T-lymphocyte-associated antigen 4; DC, Dendritic cell; DLL4, Delta-like 4; ECM, Extracellular matrix; EGFL-7, Epidermal growth factor like 7; EGFR, Epidermal growth factor receptor; Fc, Fragment, crystallizable; FDA, Food and Drug Administration; FLT3, Fms-like tyrosine kinase 3; GITR, Glucocorticoid-induced TNFR-related; IFN, Interferon; IL-2, Interleukin 2;KIT, Stem cell factor receptor; MET, Hepatocyte growth factor receptor; NCT, National clinical trial; NDA, New drug application; OX40, Cluster of differentiation antigen 134; PAP, Prostatic acid phosphatase; PD-1, Programmed death-1; PDGFR, Platelet-derived growth factor receptor; PDL1, Programmed death ligand 1; PIGF, Phosphatidylinositol-glycan biosynthesis class F protein; PPMC, Portland Providence Medical Center; RAF, Rapidly accelerated fibrosarcoma; RET, Rearranged during transfection; RP, Recombinant peptide; scFv, Single-chain Fv; SMO, Smoothened; VEGF, Vascular endothelial growth factor; VEGFR, Vascular endothelial growth factor receptor. Table adapted from reference [6] of this article (Junttila and de Sauvage) with permission from Nature, copyright 2013. Note, agents that either failed to be effective in clinical trials or have been officially terminated are removed from the current list.