Target Information

Target General Information

Target ID

T93923 (Former ID: TTDNC00406)

Target Name

Co-stimulatory molecule 4-1BB (CD137)

Synonyms

Tumor necrosis factor receptor superfamily member 9; T-cell antigen ILA; T-cell antigen 4-1BB homolog; ILA; CDw137; 4-1BB ligand receptor

Gene Name

TNFRSF9

Target Type

Clinical trial target

[1]

Disease

[+] 8 Target-related Diseases

Melanoma [ICD-11: 2C30]

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Acute myeloid leukaemia [ICD-11: 2A60]

B-cell lymphoma [ICD-11: 2A86]

Malignant haematopoietic neoplasm [ICD-11: 2B33]

Non-small cell lung cancer [ICD-11: 2C25]

Lymphoma [ICD-11: 2A80-2A86]

Mature B-cell lymphoma [ICD-11: 2A85]

Function

Possibly active during T cell activation. Receptor for TNFSF9/4-1BBL.

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BioChemical Class

Cytokine receptor

UniProt ID

TNR9_HUMAN

Sequence

MGNSCYNIVATLLLVLNFERTRSLQDPCSNCPAGTFCDNNRNQICSPCPPNSFSSAGGQR
TCDICRQCKGVFRTRKECSSTSNAECDCTPGFHCLGAGCSMCEQDCKQGQELTKKGCKDC
CFGTFNDQKRGICRPWTNCSLDGKSVLVNGTKERDVVCGPSPADLSPGASSVTPPAPARE
PGHSPQIISFFLALTSTALLFLLFFLTLRFSVVKRGRKKLLYIFKQPFMRPVQTTQEEDG
CSCRFPEEEEGGCEL

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3D Structure

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AlphaFold

HIT2.0 ID

T72U9G

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 19 Clinical Trial Drugs

Anti-CD137

Drug Info

Phase 2

Solid tumour/cancer

[2]

Urelumab

Drug Info

Phase 2

Solid tumour/cancer

[3], [4]

ADG106

Drug Info

Phase 1/2

Non-hodgkin lymphoma

[5]

CD137 CAR-T Cell

Drug Info

Phase 1/2

Acute lymphoblastic leukaemia

[6]

MG7-CART

Drug Info

Phase 1/2

Acute myeloid leukaemia

[7]

NM21-1480

Drug Info

Phase 1/2

Advanced solid tumour

[8]

AGEN2373

Drug Info

Phase 1

Solid tumour/cancer

[9]

AMG 506

Drug Info

Phase 1

Solid tumour/cancer

[10]

CD28 and CD137 CAR-T Cells

Drug Info

Phase 1

Acute lymphoblastic leukaemia

[11]

CTX-471

Drug Info

Phase 1

Solid tumour/cancer

[12]

GEN1042

Drug Info

Phase 1

Solid tumour/cancer

[13]

GEN1046

Drug Info

Phase 1

Solid tumour/cancer

[14]

INBRX-105

Drug Info

Phase 1

Solid tumour/cancer

[15]

LVGN6051

Drug Info

Phase 1

Solid tumour/cancer

[16]

MCLA-145

Drug Info

Phase 1

Lymphoma

[17]

PF-05082566

Drug Info

Phase 1

Non-hodgkin lymphoma

[18]

RG6076

Drug Info

Phase 1

Hematologic tumour

[19]

RG7827

Drug Info

Phase 1

Solid tumour/cancer

[19]

Utomilumab

Drug Info

Phase 1

Solid tumour/cancer

[20]

Mode of Action

[+] 6 Modes of Action

Agonist

[+] 8 Agonist drugs

Urelumab

Drug Info

[3]

CTX-471

Drug Info

[25]

GEN1042

Drug Info

[26]

GEN1046

Drug Info

[26]

INBRX-105

Drug Info

[27]

MCLA-145

Drug Info

[29]

RG7827

Drug Info

[19]

Utomilumab

Drug Info

[31]

Inhibitor

[+] 2 Inhibitor drugs

ADG106

Drug Info

[21]

AMG 506

Drug Info

[24]

CAR-T-Cell-Therapy

[+] 2 CAR-T-Cell-Therapy drugs

CD137 CAR-T Cell

Drug Info

[6]

MG7-CART

Drug Info

[7]

Modulator

[+] 3 Modulator drugs

NM21-1480

Drug Info

[22]

PF-05082566

Drug Info

[30]

HG-1051

Drug Info

[1]

Activator

[+] 2 Activator drugs

AGEN2373

Drug Info

[23]

LVGN6051

Drug Info

[28]

CAR-T-Cell-Therapy(Dual specific)

[+] 1 CAR-T-Cell-Therapy(Dual specific) drugs

CD28 and CD137 CAR-T Cells

Drug Info

[11]

Target Regulators

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Target-interacting Proteins

Target-interacting Proteins Info

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 1 KEGG Pathways

Cytokine-cytokine receptor interaction

NetPath Pathway

[+] 1 NetPath Pathways

TCR Signaling Pathway

PID Pathway

[+] 2 PID Pathways

Downstream signaling in na&#xef

WikiPathways

[+] 1 WikiPathways

TCR Signaling Pathway

References

Top

REF 1

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1878).

REF 2

ClinicalTrials.gov (NCT00612664) Phase II, 2nd Line Melanoma - RAND Monotherapy. U.S. National Institutes of Health.

REF 3

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 4

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 5

ClinicalTrials.gov (NCT04775680) Study of ADG106 In Combination With PD-1 Antibody In Advanced or Metastatic Solid Tumors and/or Non Hodgkin Lymphoma. U.S. National Institutes of Health.

REF 6

ClinicalTrials.gov (NCT02965092) CD19 Chimeric Antigen Receptor (CAR)-Modified T Cell Therapy in Treating Patients With B-cell Malignancies

REF 7

ClinicalTrials.gov (NCT02862704) A Study of MG7 Redirected Autologous T Cells for Advanced MG7 Positive Liver Metastases(MG7-CART)

REF 8

ClinicalTrials.gov (NCT04442126) A Study of NM21-1480 in Adult Patients With Advanced Solid Tumors. U.S. National Institutes of Health.

REF 9

ClinicalTrials.gov (NCT04121676) Anti-CD137 Monoclonal Antibody in Patients With Advanced Cancer. U.S. National Institutes of Health.

REF 10

ClinicalTrials.gov (NCT04049903) Study to Investigate the Safety, Blood Levels and Activity of MP0310 (AMG 506) in Patients With Advanced Solid Tumors. U.S. National Institutes of Health.

REF 11

ClinicalTrials.gov (NCT02186860) Chimeric Antigen Receptor (CAR)-Modified T Cell Therapy in Treating Patients With Acute Lymphoblastic Leukemia

REF 12

ClinicalTrials.gov (NCT03881488) Study of CTX-471 in Patients Post PD-1/PD-L1 Inhibitors in Metastatic or Locally Advanced Malignancies. U.S. National Institutes of Health.

REF 13

ClinicalTrials.gov (NCT04083599) GEN1042 Safety Trial in Subjects With Malignant Solid Tumors. U.S. National Institutes of Health.

REF 14

ClinicalTrials.gov (NCT03917381) GEN1046 Safety Trial in Patients With Malignant Solid Tumors. U.S. National Institutes of Health.

REF 15

ClinicalTrials.gov (NCT03809624) Study of INBRX-105 in Patients With Solid Tumors (PDL1x41BB). U.S. National Institutes of Health.

REF 16

ClinicalTrials.gov (NCT04130542) Phase 1 Trial of LVGN6051 as Single Agent and in Combination With Keytruda (MK-3475-A31/KEYNOTE-A31) in Advanced or Metastatic Malignancy. U.S. National Institutes of Health.

REF 17

ClinicalTrials.gov (NCT03922204) A Study of Bispecific Antibody MCLA-145 in Patients With Advanced or Metastatic Malignancies. U.S. National Institutes of Health.

REF 18

ClinicalTrials.gov (NCT02179918) A Study Of 4-1BB Agonist PF-05082566 Plus PD-1 Inhibitor MK-3475 In Patients With Solid Tumors (B1641003/KEYNOTE-0036). U.S. National Institutes of Health.

REF 19

Clinical pipeline report, company report or official report of Roche.

REF 20

ClinicalTrials.gov (NCT01307267) A Study Of PF-05082566 As A Single Agent And In Combination With Rituximab. U.S. National Institutes of Health.

REF 21

Clinical pipeline report, company report or official report of Adagene.

REF 22

Clinical pipeline report, company report or official report of Numab Therapeutics.

REF 23

Clinical pipeline report, company report or official report of Agenus.

REF 24

Clinical pipeline report, company report or official report of Amgen.

REF 25

Clinical pipeline report, company report or official report of Compass Therapeutics.

REF 26

Clinical pipeline report, company report or official report of Genmab.

REF 27

Clinical pipeline report, company report or official report of Inhibrx.

REF 28

Optimization of 4-1BB antibody for cancer immunotherapy by balancing agonistic strength with FcR affinity. Nat Commun. 2019 May 20;10(1):2141.

REF 29

Clinical pipeline report, company report or official report of Merus.

REF 30

Targeting of 4-1BB by monoclonal antibody PF-05082566 enhances T-cell function and promotes anti-tumor activity. Cancer Immunol Immunother. 2012 Oct;61(10):1721-33.

REF 31

First-in-Human Study of Utomilumab, a 4-1BB/CD137 Agonist, in Combination with Rituximab in Patients with Follicular and Other CD20 + Non-Hodgkin Lymphomas. Clin Cancer Res. 2020 Jun 1;26(11):2524-2534.

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