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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.
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BMC Medicine

ISSN: 1741-7015

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