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Table 1 Summary of current strategies targeting myeloid cells in clinic

From: Emerging strategies in targeting tumor-resident myeloid cells for cancer immunotherapy

Function

Target molecule

[Ref]

Agents

Total # trials

Combination agents

Tumor types

Trial phases

Monotherapy

Combination

Proliferation, differentiation, and recruitment

CCR2

[165,166,167,168,169,170,171,172]

BMS-8113160

0

5

PD-1, chemotherapy, radiation, vaccine

CRC, hepatic, lung, pancreatic, renal

1/2, 2

CSF1R

[173,174,175,176,177,178,179,180,181,182,183,184,185,186]

Axatilimab, Emactuzumab, Bezuclastinib, Pexidartinib, Cabiralizumab, Lacnotuzumab, PD-0360324, IMC-CS4

5

14

BRAF, MEK, mTOR, PD-L1, PD-1, TKI, VEGF-A, chemotherapy, radiation, vaccine

Biliary, breast, fallopian, GIST, H&N, mastocytosis, melanoma, myeloid, lymphoma, ovarian, pancreatic, peritoneal, sarcoma, solid

1, 1/2, 2, 3

CXCR1/2

[187,188,189,190,191,192,193]

SX-682, AZD5069, Navarixin

1

7

ADT, CTLA-4, PD-1, PD-L1, TGFβ-β, vaccine

CRC, melanoma, myeloid, pancreatic, prostate, solid

1, 1/2, 2

FLT3

[68, 194,195,196,197,198,199,200]

CXD-301

0

11

CD40, PD-1, TLR3, chemotherapy, radiation, vaccine

Breast, H&N, lung, lymphoma, melanoma, prostate, solid

1, 1/2, 2

STAT3

[201,202,203,204,205,206,207,208]

Danvatirsen, WP1066, TTI-101, OPB-111077, Napabucasin

4

9

Bcl-2, CTLA-4, DNMT, PD-L1, chemotherapy, radiation

Bladder, CNS, CRC, lung, lymphoma, melanoma, myeloid, pancreatic, solid

1, 1/2, 2, 3

Siglec-15

[401,402,403,404,405,406,407,408]

NC318*

1

1

PD-1

Lung, solid

1/2, 2

TREM2

[409,410,411,412,413]

PY314*

0

1

PD-1

Solid

1

Functional blockade

CD47

[209,210,211,212,213,214,215, 217, 218, 220, 221]

Magrolimab, Evorpacept,

CC-90002, SRF231

Letaplimab, Lemzoparlimab, AO-176, TJ011133, SHR-1603,

ZL-1201

3

18

Bcl-2, CCR4, CD20, CD38, DNMT, E3 ligase, GD2, PD-1, PD-L1, proteasome, VEGF-A, chemotherapy

GU, lymphoma, malignant heme, myeloma, myeloid, neuroblastoma, osteosarcoma, solid

1, 1/2, 2, 3

SIRPɑ

[209, 210, 212, 214, 216, 219, 222]

GS-0189, CC-95251, BI765063, TTI-621, TTI-622, Evorpacept,

TG-1801, IMM0306, SL-172154, HX009, IBI322

10

21

Bcl-2, CD20, CD38, DNMT, E3 ligase, HER2, PD-1, proteasome, VEGFR2, chemotherapy, radiation

Cancer, CRC, esophageal, fallopian, gastric, H&N, lymphoma, malignant heme, myeloma, myeloid, ovarian, peritoneal, sarcoma, solid,

1, 1/2, 2, 2/3

Polarization

TLR9

[235,236,237,238,239,240,241,242,243]

CpG, CpG-STAT3 siRNA CAS3/SS3, CMP-001, Tilsotolimod,

SD-101

1

16

4-1BB, ADT, BTK, CTLA-4, GnRH, OX-40, PD-1, PD-L1, radiation

Biliary, breast, CRC, hepatic, lymphoma, melanoma, pancreatic, prostate, solid

1, 1/2, 2

CD40

[245,246,247,248,249,250,251,252,253,254,255,256,257]

Selicrelumab, Mitazalimab, CDX-1140, 2141-V11, Sotigalimab*, Dacetuzumab, Medi5068, ChiLob7/4, SEA-CD40, LOAd703, NG-350A

7

26

CD3, CSF1R, CTLA-4, EGFR, FLT3L, PD-1, PD-L1, TLR3, VEGF-A, chemotherapy, radiation, cellular therapies

Bladder, breast, CNS, CRC, esophageal, gastric, GI, lung, lymphoma, melanoma, ovarian, pancreatic, renal, sarcoma, solid,

1, 1/2, 2

PI3Kγ

[258,259,260,261,262,263,264,265,266,267,268,269]

Eganelisib*

1

3

PD-1, PD-L1, VEGF-A, chemotherapy

Breast, H&N, renal, solid

1, 2

LILRB2

[425,426,427,428,429,430]

MK-4830, JTX 8064, IO-108

0

11

CTLA-4, PD-1, TIGIT, vaccine

CRC, lung, melanoma, renal, solid

1, 1/2, 2

CLEVER-1

[431,432,433,434,435]

Bexmarilimab

2

1

PD-1

CRC, lung, renal, solid

1, 1/2

Metabolic reprogramming

CD73

[271,272,273,274,275,276,277,278,279]

Quemliclustat, LY3475070, Oleclumab, Mupadolimab, Sym021, IBI325, JAB-BX102, INCA00186, Uliledlimab*, NZV930, BMS-986179, HLX23, AK119, GS-1423

2

34

A2AR, A2BR, CTLA-4, EGFR, NKG2A, PD-1, PD-L1, VEGF-A, chemotherapy, radiation

Bladder, breast, CRC, lung, pancreatic, prostate, sarcoma, solid

1, 1/2, 2, 3

CD39

[275, 277, 280, 281]

TTX-030, SRF617, IPH5201, ES002

0

5

A2AR, A2BR, CD73, PD-1, chemotherapy

Lymphoma, prostate, solid

1, 2

A2AR

[283,284,285]

Taminadenant, Ciforadenant, AZD4635*, Inupadenant

1

14

ADT, CD38, CD73, HIF2α, LAG3, PD-1, PD-L1, TIGIT, chemotherapy

Breast, lung, lymphoma, myeloma, prostate, renal, solid

1, 1/2, 2

A2BR

[283]

PBF-1129

1

1

PD-1

Lung

1

A2AR

A2BR

[286]

Etrumadenant

0

11

ADT, CD39, CD73, IL-6, PD-1, PD-L1, TIGIT, VEGF-A, chemotherapy

CRC, H&N, lung, pancreatic, prostate

1, 1/2, 2

IDO1

[287,288,289,290,291]

Epacadostat*,

BMS-986205, KHK2455

navoximod, EOS200271, LY3381916,

MK-7162

1

22

IL-15, LAG3, mTOR, PD-1, PD-L1, TGFβ-β, VEGF-A, chemotherapy, radiation, vaccine

Bladder, CNS, CRC, endometrial, fallopian, gastric, H&N, pancreatic, peritoneal, prostate, solid, urothelial

1, 1/2, 2, 3

Epigenetic reprogramming

HDAC

[297, 299,300,301,302,303,304,305,306,307,308,309]

Entinostat*, Romidepsin, Tucidinostat, Mocetinostat, Domatinostat, Vorinostat*, Belinostat, Abexinostat, Panobinostat, Givinostat, Resminostat, Ricolinostat

17

147

AI, Bcl-2, BET, BTK, CD30, CD38, CDK 4/6, CTLA-4, DNMT, DRD2, E3 ligase, ER, GD2, GnRH, IL-2, IL-12, JAK, MEK, mTOR, NAE, ODC, PARP, PI3K, proteasome, PD-1, PD-L1, RT, TGFβ-β, TKI, VEGF-A, chemotherapy, radiation, cellular therapies

ALL, anal, bladder, breast, cervical, CNS, CRC, esophageal, fallopian, gastric, H&N, lung, lymphoma, melanoma, Merkel, MPN, myeloid, myeloma, neuroendocrine, ovarian, pancreatic, penile, peritoneal, prostate, renal, sarcoma, solid, urothelial, vulvar

1, 1/2, 2, 2/3, 3

Cytokines

STING

[311, 312, 314,315,316,317]

BMS-986301, E7766, Ulevostinag,

MK-2118, GSK3745417, TAK-676, SB11285, IMSA101

IACS-8803*, MIW815

1

9

CTLA-4, PD-1, PD-L1, radiation

Breast, H&N, lymphoma, solid

1, 1/2, 2

IFNγ

[319,320,321,322]

IFNγ 1b

1

2

HER2, PD-1, chemotherapy

Breast, lymphoma, myeloid, sarcoma

1, 1/2, 2

IL-12

[323,324,325,326,327,328,329,330,331,332,333]

M9241*, GEN-1*, MEDI1191*, SAR441000

0

9

ADT, PARP, PD-1, PD-L1, TGF-β, chemotherapy, radiation

Breast, GU, lymphoma, ovarian, prostate, solid

1, 1/2, 2

TNFR2

[334,335,336,337,338,339,340,341,342,343]

HFB200301,

BI-1808,

APX601, BITR2101, SIM0235

2

0

N/A

Solid

1, 1/2

IL-1β

[344,345,346,347,348,349]

Canakinumab, Anakinra, Gevokizumab

7

14

EPO, LAG3, PD-1, PD-L1, TIM-3, TKI, VEGF-A, VEGFR2, chemotherapy, radiation, cellular therapies

Breast, CRC, CLL, esophageal, gastric, lung, lymphoma, melanoma, myeloid, myeloma, pancreatic, prostate, renal

1, 1/2, 2, 3

IL-6

[351, 353,354,355,356]

Tocilizumab, Sarilumab, Siltuximab*,

Sirukumab, Olokizumab, Clazakizumab

0

10

CD3, CEA, CTLA-4, HER2, PD-1, PD-L1, chemotherapy, radiation

Breast, GU, lung, melanoma, pancreatic

1, 1/2, 2

IL-8

[192, 193]

HuMax-IL8,

0

8

CDA, CTLA-4, DNMT, PD-1, radiation

H&N, hepatic, lung, myeloid, pancreatic, prostate, solid

1, 1/2, 2

IL-10

[357,358,359,360,361,362,363]

Pegilodecakin

0

1

PD-1, TKI, chemotherapy

Solid

1

TGFβ

[364,365,366,367,368,369,370]

TASO-001, Galunisertib, Vactosertib, LY3200882, PF-06952229, AVID200, ABBV-151, SAR439459, NIS793, BCA101

trabedersen, ISTH0036, gemogenovatucel-T, belagenpumatucel-L,

A83-01, SB-43-1542, RepSox, SM16, Bintrafup alfa, XPA-42-089

4

28

ADT, CD38, CDK 4/6, E3 ligase, IL-2, JAK, PD-1, PD-L1, TIM-3, VEGF-A, VEGFR2, chemotherapy, radiation

Breast, CNS, CRC, esophageal, hepatic, gastric, H&N, lung, MPN, myeloid, myeloma, ovarian, pancreatic, prostate, solid, urothelial

1, 1/2, 2, 3

  1. *Indicates potentially significant results in clinical setting