Empowered by state-of-the-art technologies and advanced platforms in the field of antibody discovery and immunotherapy, Creative Biolabs offers world-leading chimeric antigen receptor macrophage (CAR-MA) services for solid tumor treatment with academic purposes. https://www.creative-biolabs.com/car-t/one-stop-car-ma-therapy-development.htm

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TARGETING MACROPHAGES
FOR TUMOR IMMUNOTHERAPY
Other Immunocytotherapy Development
Services & Products:
· CAR-MA Vector · CAR-MA Cell
· CAR-T/TCR-T · CAR-NK/TCR-NK
One-Stop CAR-MA Therapy Development:
· CAR Design & Construction
· CAR-MA Preparation
· Macrophage Activation and Expansion
WHAT WE DO:
Functions of macrophages in
cancers are categorized into
four types: (1) promotion of
angiogenesis; (2) induction of
invasiveness and metastasis;
(3) regulation of the
tumor microenvironment; and
(4) induction of therapeutic
resistance.
Strategies for targeting macro-
phages for tumor immunother-
apy are categorized into six
types. (1) Suppression of
macrophage recruitment.
Inhibitors or antibodies
against molecules (or some of
their ligands) contribute to the
infiltration of macrophages
into tumors could suppress
the recruitment of macro-
phages. (2) Reduction of
macrophage survival. CSF1
inhibitors restrain the forma-
tion of macrophages. Trabec-
tedin reduces the survival of
macrophages. Immunotoxins
targeting scavenger recep-
tor-A or FRβ can deplete
TAMs. (3) Inhibition of
tumor-promoting functions.
TIM-3 blocking antibody is
reported to regulate the
activation of TAMs. Blocking
immune checkpoints on
macrophages could relieve
the function of other immune
cells. (4) Removal of the
macrophage blockade.
Interactions between CD47 on
tumors and SIRPα on macro-
phages help tumor cells evade
macrophage phagocytosis. (5)
Induction of repolarization.
Several factors can induce M1
polarization, such as IFNγ.
Factors inhibiting M2 polariza-
tion, such as CSF1R inhibi-
tors, can also reduce the
tumor burden. (6) Modification
of effector cells. Chimeric
antigen receptor (CAR)
macrophages similar to
CAR-T cells have been used
to enhance tumoricidal
functions.
Creative Biolabs
Cellular Therapy
Solutions
Apoptosis
Formation
HIF-1α
Hypoxia
Angiogenesis
Invasiveness
and metastasis
Regulating tumor microenvironment Therapeutic resistance
Primary tumor
Macrophage (Mφ)
M1φ
B cell
T cell
NK cell
M2φ
CAR
Tumor cell
Normal cell
Fibrosis
Metastasis lesion
Treg
Radiotherapy Chemotherapy
Th17
Functions of Macrophages in Cancers
1
Strategies for Targeting Macrophages for Tumor Immunotherapy
2
Modifying effector cells
Suppressing recruitment
Inducing repolarization
Removing the block
Inhibiting tumor-promoting function
Reducing survival
Inhibiting angiogenesis:
anti-VEGF/anti-VEGFR,
tyrosine kinase inhibitors
Targeting immunosuppression:
aspirin, inhibitors or antibodies of
IDO, haeme oxygenase,
arginase,TGF-β, IL-10, PD-L1,
PD-L2, B7-H4, VISTA, B7-1, B7-2
Inducing M1 polarization: IFNγ, CD40
agonists, inhibitors of PI3Kγ, mTOR,
DICER, TLR agonists of TLR4, 7, 8 or
9, methionine sulfoximine, HDAC
inhibitors, MARCO antibody
Inhibitors or antibodies against
CCL2/5, CCR2/5, CSF1, CSF1R,
VEGF, VEGFR, ITGA4, CXCR4,
C5a, NRP1, ANG2, et al.
CSF1 inhibitors, trabectedin,
bisphosphonates, immuno-
toxins against scavenger
receptor-A or FRβ
Matrix metalloproteinases,
matrix remodeling enzymes,
urokinase plasminogen
activator, cathepsin, IL-1ra,
TGF-β, growth factors,
exosomes, integrin α4,
CCL2, leukotriene B4, et al.
Adrenomedullin,
thymidine
phosphorylase,
sema4d,
WNT7B,
WNT5A,
WNT11, VEGF,
CXCL12, TNF-α,
IL-1β, IL-8, et al.
Inhibiting M2 polarization: CSF1R
inhibitors, corosolic acid, omeprazole,
Gpr132 inhibitors, MEK/STAT3
inhibitors, fasting-mimicking diets,
antibodies of IL-4, IL-4Ra, IL-13
IL-6, TNF-α, cathepsin B
and S, exosomes,
metabolites, et al.
CAR-macrophage
targeting CD19,
HER2 mesothelin,
et al.
Antibodies
against CD47,
SIRPα, MUC1,
EGFR, et al.
Inhibiting
activation: TIM-3
blocking antibody
Glycolysis
Immune cell represented
by T cell
e.g. cytotoxic T cell:
activation
infiltration
proliferation
function