Skip to main content
. 2024 Jun 11;17:44. doi: 10.1186/s13045-024-01559-0

Table 3.

Macrophage-based clinical interventions

Therapy Mechanism of action Tumor type Clinical Trial Phase Study Status
Inhibition of Macrophage Recruitment

Carlumab

(CNTO 888)

 CCL2 blockade, to inhibit angiogenesis, macrophage infiltration and tumor invasion, which favor tumor growth and metastasis Prostate cancer NCT00992186 Phase II clinical trial [279] Completed

Emepticap pegol

(mNOX-E36)

 CCL2 inhibition and therefore, of TAMs recruitment. In addition, it improves antiangiogenic treatment GBM - Preclinical phase [281] -
FOLFIRINOX + PF-04136309 CCR2 inhibition Pancreatic neoplasms NCT01413022 Phase I clinical trial [282] Completed

BMS-813,160

+

Chemotherapy or Nivolumab

 CCR2-CCL2 axis blockade by antagonists

Pancreatic and colorectal cancer

PDAC

NCT03184870

NCT03767582

 Phase Ib/II clinical trial [283]

Completed

Ongoing
Pexidartinib (PLX3397) + paclitaxel CSF-1R inhibition Solid tumors NCT01525602 Phase Ib clinical trial [288] Completed

Pexidartinib

(PLX3397)

 CSF-1R inhibition TGCT, EAC NCT04488822 Phase III clinical trial [289]; Preclinical phase [361] Ongoing
Emactuzumab CSF1R activation inhibition, leading to the recruitment of CSF1R-expressing macrophages that constitute the tumor mass TGCT NCT05417789 Phase III clinical trial [290] Ongoing

BL-8040 +

Pembrolizumab

CXCR4 inhibition and

PD-1 blockade

Pancreatic

cancer

 NCT02907099 Phase IIb clinical trial [293] Completed

LY2510924 +

Durvalumab

CXCR4 inhibition and

PD-1 blockade

 Solid tumors NCT02737072 Phase Ia clinical trial [294] Completed

PF-06747143

with and without chemotherapy

 CXCR4 inhibition Acute myeloid leukemia NCT02954653 Phase I clinical trial [295] Completed
Tinengotinib (TT-00420) CSF-1R inhibition Breast cancer - Preclinical phase [362] -
Plerixafor CXCR4 inhibition

Colorectal

ovarian

pancreatic

cancer

NCT02179970

NCT03277209

 Phase I clinical trial [no results] Completed

BMS-936,564

+

lenalidomide/

dexamethasone

or bortezomib/

dexamethasone

 CXCR4 inhibition MM NCT01359657 Phase Ib clinical trial [363] Completed
TAMs repolarization
3D185 FGFR1/2/3 inhibition and CSF-1R kinase activity Bladder breast and urothelial cancer, MM, NSCLC, LSCC, GA - Preclinical phase [297] -

Pexidartinib

(PLX3397)

 CSF-1R inhibition

OS

FS

PDAC

 - Preclinical phase [298, 302] -
MGN1703 TLR9 agonist Small-cell lung cancer NCT02200081 Phase II clinical trial [306] Completed
GSK1795091 TLR4 agonist Neoplasms NCT03447314 Phase I clinical trial [307] Completed

LHC165

or

LHC165 + PDR001

 TLR7 agonist Solid tumors NCT03301896 Phase I/Ib clinical trial [308] Completed
RRX-001 NLRP3 inhibition, inducer of Nrf2 and NO superagonist Small cell lung cancer NCT03699956 Phase II clinical trial [311] Completed
Metformin Reduces oxidative phosphorylation and increases glycolysis OS -

Preclinicalphase

[314]

 -
2-desoxiglucose (2DG) hexokinase inhibition Pancreatic cancer -

Preclinicalphase

[315]

 -
NCX-4016 NO release

Colon carcinoma and

hepatoma

 -

Preclinicalphase

[316]

 -

Tenalisib

(RP6530)

 Inhibits PI3Kδ/γ

T cell lymphoma

Hodgkin lymphoma

 NCT02017613

Phase I/II clinical trial

[317]

Preclinical phase [318]

 Completed
Genetic deletion of ABC transporters Cholesterol efflux blockage Metastatic ovarian cancer - Preclinical phase [319] -
IFN-γ Induction of NOS2 transcription, which increases NO production in cancer cells, leading them to apoptosis and ferroptosis

Hepatoma

Melanoma

Colorectal cancer

RCC

 - Preclinical phase [320] -
L-norvaline ARG-1 inhibition

Breast

cancer

 - Preclinical phase [321] -

Manganese-

Albumin Nanocomplex

 Activation of TLR4 Melanoma - Preclinical phase [323] -
CART-mRNA complexes Positive regulation of proinflammatory cytokines Melanoma and B cell lymphoma - Preclinical phase [324] -

Dimannose-

functionalized biodegradable polymeric NPs containing mRNA

 Phosphorylate and activate IRF5 to increase the expression of M1 genes and decrease the expression of M2 genes Ovarian, melanoma cancer and GBM - Preclinical phase [325] -
VEGF and PIGF siRNA VEGF and PIGF inhibition Breast cancer - Preclinical phase [328] -

Tenalisib

(RP6530)

+ romidepsin

 Inhibits PI3Kδ/γ T cell lymphoma NCT03770000 Phase I/II clinical trial [364] Completed
Depletion of M2-like TAMs

Pexidartinib

(PLX3397)

 CSF-1R inhibition Colorectal cancer and mesothelioma - Preclinical phase [259] -
Melittin derived peptide-drug conjugate (M-DM1) Inhibition of tubulin polymerization by inducing M2 macrophage apoptosis Melanoma - Preclinical phase [330] -
Pembrolizumab (MK-3475) PD-1 blockade

Melanoma

NSCLC

 NCT01295827 Phase I clinical trial [332] Completed
Zoledronic acid + doxorubicin Macrophage depletion and increased anti-tumor activity of doxirubicin Lewis lung carcinoma - Preclinical phase [335] -

Zoledronate

(Bisphosphonate)

 Induction of apoptosis of TAMs and suppresses the release of proangiogenic Breast cancer NCT02347163 Phase II clinical trial [336] Completed
Lipid NPs loaded with doxorubicin Inmunosupresion of CD163 + TAMs Melanoma - Preclinical phase [340] -
Clo-LipoDOTAP Disruption of the mitochondrial respiratory chain, cytotoxicity against M2 Melanoma - Preclinical phase [341] -
Trabectedin

Targets TRAIL-R1/2, inducing direct caspase-8

dependent apoptosis

 CLL - Preclinical phase [344] -
Trabectedin

Targets TRAIL-R1/2, inducing direct caspase-8

dependent apoptosis

 Melanoma, pancreatic and metastatic prostate tumour - Preclinical phase [345–347] -

Trabectedin +

Ipilimumab +

Nivolumab

 Targets TRAIL-R1/2, inducing apoptosis. PD-1 and CTLA-4 receptor inhibition Sarcoma NCT03138161 Phase I/II clinical trial [348] Ongoing

Combination of nivolumab-

ipilimumab + lurbinectedin

 Induction apoptosis, inhibition the production of inflammatory/growth factors (CCL2, CXCL8 and VEGF) and affected monocyte adhesion and migration capacity Small cell lung cancer NCT04610658 Phase I/II clinical trial [no results] Completed

Lurbinectedin +

Atezolizumab

 Induction apoptosis and PD-1 blockade Small cell lung cancer NCT04253145 Phase I/II clinical trial [no results] Ongoing

Erlotinib derivative

(TD-92)

 Potentiates the antitumor effect of anti-PD-1 and reduces TAMs by down-regulation of CSF-1R NSCLC - Preclinical phase [349] -

Emactuzumab

+

Atezolizumab

 Inhibition of CSF-1R Metastatic solid tumors NCT02323191 Phase I clinical trial [350] Completed
Promoting phagocytosis of TAMs
MiR-340 CD47 suppression Pancreatic cancer - Preclinical phase [85] -
Anti-CD47 blocking mAbs Blockade of the interaction between CD47-SIRP-α Colon carcinoma - Preclinical phase [354] -
PEP-20 polypeptide Blockade of CD47 and its interaction with SIRPα

Colon carcinoma,

melanoma

 - Preclinical phase [355] -
HU5F9-G4 cytokine Enhancement of macrophage phagocytosis by blocking CD47 Solid tumors NCT02216409 Phase I clinical trial [356] Completed
Humanized AB21 Anti-SIRPα antibody, targets SIRPα to promote the phagocytosis of TAMs

Colon carcinoma,

breast cancer and

Burkitt lymphoma

 - Preclinical phase [357] -

TTA-Q6

+

RRX-001

 TTA-Q6 disrupts calcium uptake by cancer cells, activating calreticulin on their surface and triggering immune responses. RRX-001 reduces CD47 protein, preventing cancer cells from evading the immune system Lung cancer - Preclinical phase [358] -

HBPdC

(palladium-based bioorthogonal nanoplatform)

 ROS production and M1 macrophage polarization. Reduction of CD47 promoting phagocytosis. Activation of sequestered prodrugs by bioorthogonal catalysis, allowing chemotherapy Breast cancer - Preclinical phase [360] -

Abbreviations AML, acute myelogenous leukemia; CCL2, cytokine (C-C motif) ligand 22; CCR2, cytokine (C-C motif) receptor 2; CLL, chronic lymphocytic leukemia; CSF-1, colony stimulating factor 1; CSF-1R, colony-stimulating factor-1 receptor; DLBCL, diffuse large B-cell leukemia; EAC, esophageal adenocarcinoma; EGF1, epidermal growth factor 1; FGFR, fibroblast growth factor receptor; FL, follicular lymphoma; FS, fibrosarcoma; GA, gastric adenocarcinoma; GBM, glioblastoma multiforme; IFN-γ, interferon-gamma; LSCC, lung squamous cell carcinoma; MM, multiple myeloma; NLRP3, NOD-like receptor family pyrin domain containing 3; NO, nitric oxide; NOS2, nitric oxide synthase 2; NPs, nanoparticles; Nrf2, nuclear factor erythroid 2-related factor 2; NSCLC, non-small cell lung cancer; OS, osteosarcoma; PDAC, pancreatic ductal adenocarcinoma; PI3Kδ/γ, phosphoinositide 3-kinase delta/gamma; PIGF, placental growth factor; RCC, renal cell carcinoma; ROS, reactive oxygen species; TAMs, tumor associated macrophages; TGCT, tenosynovial giant cell tumor; TLR, toll-like receptor; TME, tumor microenvironment; VEGF, vascular endothelial growth factor