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Page 8 of 13 Dello Russo et al. Neuroimmunol Neuroinflammation 2018;5:36 I http://dx.doi.org/10.20517/2347-8659.2018.42

Table 1. Drugs targeting GAMs’ functions within the glioblastoma microenvironment
Drug name and approval Drug properties Molecular Pharmacological Other effects Clinical outcome Ref.
status target actions on GAMs
Preclinical evidence
Amphotericin B Small MW compound Toll-like recep- ↑ GAM’s tumor No direct antipro- ↓ Tumor growth [52, 53]
Approved for clinical use tors infiltration liferative effects on
by FDA and in EU mem- ↑ GAMs’ antitumor GSCs in vitro ↑ Survival
ber states immune activation
↑ iNOS expression
and NO production
Cyclosporine A Small MW compound Calcineurin/ ↓ GAMs’ tumor ↑ TGFβ and VEGF ↓ Tumor growth [9,31,32]
Approved for clinical use NFAT1 infiltration ↓ DNA repair
by FDA and in EU mem- ↓ IL10, ARG1 and ↓ miR195 and other Potential tumor
ber states GM-CSF miRNAs promoting activities
↓ MMP2
Minocycline Small MW compound p38-MAPK ↓ MT1-MPP, ↓ MMP- ↓ Pro-inflammary cy- ↓ Tumor growth [40,75,76]
Approved for clinical use 9 production by tokines by microglia
by FDA and in EU mem- GAMs ↓ MCP-1 by glioma ↑ Survival
ber states ↓ Tumor cells’ migra- cells
tion
Nivolumab Biologic PD-1 ↑ GAMs’ tumor ↑ Protective effects No survival benefits [37]
Approved for clinical use (mAb) infiltration of BG324 per se
by FDA and EMA ↑ AXL kinase activity
mTOR kinase Small MW compound mTOR kinase ↑ Pro-inflammatory Direct antiprolifera- ↓ Tumor growth [55,57,58]
inhibitors activation of microg- tive effects
Approved/ lia in vitro
investigational drugs
BGB324 Small MW compound Receptor tyro- ↓ CD11b+ GAMs’ ↑ Survival [37]
(R428) sine kinase AXL tumor infiltration
Investigational ↓ CD45+ leukocyte
tumor infiltration
BLZ945 Small MW compound CSF-1R ↑ survival of GAMs ↑/↓ GAMs’ tumor ↓ Tumor growth [36,37]
Investigational ↑ GAMs’ phagocytic infiltration
activity ↑ Survival
↓ GAMs’ protumor
immune activation
CHA Small MW compound STAT ↑ GAMs’ antitumor ↓ Tumor growth [67]
Investigational factors immune activation
Propentofylline Small MW compound Phosphor- ↓ MMP-9 by GAMs ↓ Migratory capac- ↓ Tumor growth [78]
Investigational diesterase ity of microglia and
glioma
TRAM-34 Small MW compound KCa3.1 channels ↑ GAMs’ antitumor ↓ Tumor growth [60]
Investigational immune activation
Vosaroxin Small MW compound DNA and ↑ GAMs’ tumor ↓ Tumor growth [66]
Investigational TOPO-II infiltration
↑ GAMs’ antitumor
immune activation
Peptide R Synthetic peptide CXCR4 ↑ GAMs’ antitumor ↓ Glioma invasive- ↓ Tumor growth [64]
Investigational immune activation ness,
↓ Intratumor vessel
formation
RGD peptides Synthetic peptides Integrins ↓ GAMs’ tumor ↓ GSC-secreted ↓ Tumor growth [44]
Investigational infiltration periostin
↑ GAMs’ antitumor
immune activation
IL-12 or Biologic IL-12 receptor ↑ GAMs’ tumor ↑ IFNγ and IL-12 ↓ Tumor growth [61,62]
rAAV2-mediated IL-12 (protein or engineered infiltration intratumoral levels
Investigational viral vector) ↑ GAMs’ antitumor induced by rAAV2. ↑ Survival
immune activation
↑ GAMs’ phagocytic
activity
miR-142-6p Biologic mRNA ↑ GAMs’ tumor ↓ Tumor growth [63]
Investigational (Synthetic oligonucle- infiltration
otide) ↑ GAMs’ antitumor ↑ Survival
immune activation
X7Ab Biologic ACKR3 / CXCR7 ↑ GAMs’ antitumor Increased therapeu- ↓ Tumor growth [68]
Investigational (single-chain anti- immune activation tic effects of TMZ
body) ↑ Survival