Target Information

Target General Information

Target ID

T67805 (Former ID: TTDC00337)

Target Name

CD70 antigen (CD27-L)

Synonyms

Tumor necrosis factor ligandsuperfamily member 7; Tumor necrosis factor ligand superfamily member 7; TNFSF7; CD27LG; CD27L; CD27 ligand

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Gene Name

CD70

Target Type

Clinical trial target

[1]

Disease

[+] 10 Target-related Diseases

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

Acute myeloid leukaemia [ICD-11: 2A60]

Diabetes mellitus [ICD-11: 5A10]

Malignant haematopoietic neoplasm [ICD-11: 2B33]

Mature T-cell lymphoma [ICD-11: 2A90]

Myelodysplastic syndrome [ICD-11: 2A37]

Ovarian cancer [ICD-11: 2C73]

Pancreatic cancer [ICD-11: 2C10]

Renal cell carcinoma [ICD-11: 2C90]

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

Function

Plays a role in T-cell activation. Induces the proliferation of costimulated T-cells and enhances the generation of cytolytic T-cells. Cytokine that binds to CD27.

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BioChemical Class

Cytokine: tumor necrosis factor

UniProt ID

CD70_HUMAN

Sequence

MPEEGSGCSVRRRPYGCVLRAALVPLVAGLVICLVVCIQRFAQAQQQLPLESLGWDVAEL
QLNHTGPQQDPRLYWQGGPALGRSFLHGPELDKGQLRIHRDGIYMVHIQVTLAICSSTTA
SRHHPTTLAVGICSPASRSISLLRLSFHQGCTIASQRLTPLARGDTLCTNLTGTLLPSRN
TDETFFGVQWVRP

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3D Structure

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AlphaFold

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 11 Clinical Trial Drugs

JNJ-74494550

Drug Info

Phase 2

Myelodysplastic syndrome

[2]

4SCAR19 and 4SCAR70

Drug Info

Phase 1/2

B-cell lymphoma

[1]

AMG 172

Drug Info

Phase 1

Renal cell carcinoma

[3]

Anti-hCD70 CAR transduced PBL

Drug Info

Phase 1

Ovarian cancer

[4]

BMS-936561

Drug Info

Phase 1

Haematological malignancy

[5]

CTX130

Drug Info

Phase 1

T-cell lymphoma

[6]

MDX-1203

Drug Info

Phase 1

Solid tumour/cancer

[7]

MDX-1411

Drug Info

Phase 1

Solid tumour/cancer

[8]

SEA-CD70

Drug Info

Phase 1

Acute myeloid leukaemia

[9]

SGN-70

Drug Info

Phase 1

Autoimmune diabetes

[10]

SGN-CD70A

Drug Info

Phase 1

Non-hodgkin lymphoma

[11]

Discontinued Drug(s)

[+] 1 Discontinued Drugs

Vorsetuzumab mafodotin

Drug Info

Discontinued in Phase 1

Renal cell carcinoma

[12]

Mode of Action

[+] 4 Modes of Action

CAR-T-Cell-Therapy(Dual specific)

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

4SCAR19 and 4SCAR70

Drug Info

[1]

Modulator

[+] 2 Modulator drugs

AMG 172

Drug Info

[14]

BMS-936561

Drug Info

[15]

CAR-T-Cell-Therapy

[+] 1 CAR-T-Cell-Therapy drugs

Anti-hCD70 CAR transduced PBL

Drug Info

[4]

Inhibitor

[+] 1 Inhibitor drugs

SEA-CD70

Drug Info

[19]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Tissue Distribution Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Tissue Distribution

Human Pathway Affiliation

Biological Network Descriptors

There is no similarity protein (E value < 0.005) for this target


Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

KEGG Pathway	Pathway ID	Affiliated Target	Pathway Map
Cytokine-cytokine receptor interaction	hsa04060	Affiliated Target
Class: Environmental Information Processing => Signaling molecules and interaction	Pathway Hierarchy

Degree	1	Degree centrality	1.07E-04	Betweenness centrality	0.00E+00
Closeness centrality	1.43E-01	Radiality	1.17E+01	Clustering coefficient	0.00E+00
Neighborhood connectivity	2.00E+00	Topological coefficient	1.00E+00	Eccentricity	13
Download	Click to Download the Full PPI Network of This Target

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 1 KEGG Pathways

Cytokine-cytokine receptor interaction

NetPath Pathway

[+] 3 NetPath Pathways

IL2 Signaling Pathway

TNFalpha Signaling Pathway

RANKL Signaling Pathway

Reactome

[+] 1 Reactome Pathways

TNFs bind their physiological receptors

References

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REF 1

ClinicalTrials.gov (NCT03125577) Combination CAR-T Cell Therapy Targeting Hematological Malignancies

REF 2

ClinicalTrials.gov (NCT04264806) A Study of Cusatuzumab in Combination With Azacitidine Compared With Azacitidine Alone in Patients With Higher-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) and Who Are Not Candidates for Hematopoietic Stem Cell Transplantation (HSCT). U.S. National Institutes of Health.

REF 3

ClinicalTrials.gov (NCT01497821) AMG 172 First in Human Study in Patients With Kidney Cancer. U.S. National Institutes of Health.

REF 4

ClinicalTrials.gov (NCT02830724) Administering Peripheral Blood Lymphocytes Transduced With a CD70-Binding Chimeric Antigen Receptor to People With CD70 Expressing Cancers

REF 5

J Clin Oncol 32:5s, 2014 (suppl, abstr 2558).

REF 6

ClinicalTrials.gov (NCT04502446) A Safety and Efficacy Study Evaluating CTX130 in Subjects With Relapsed or Refractory T or B Cell Malignancies (COBALT-LYM). U.S. National Institutes of Health.

REF 7

ClinicalTrials.gov (NCT00944905) Study of MDX-1203 in Subjects With Advanced/Recurrent Clear Cell Renal Cell Carcinoma (ccRCC) or Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma (B-NHL). U.S. National Institutes of Health.

REF 8

ClinicalTrials.gov (NCT00730652) Study of MDX-1411 in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia or Mantle Cell Lymphoma. U.S. National Institutes of Health.

REF 9

ClinicalTrials.gov (NCT04227847) A Safety Study of SEA-CD70 in Patients With Myeloid Malignancies. U.S. National Institutes of Health.

REF 10

2011 Pipeline of Seattle Genetics.

REF 11

ClinicalTrials.gov (NCT02216890) Safety Study of SGN-CD70A in Cancer Patients. U.S. National Institutes of Health.

REF 12

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020387)

REF 13

Targeting CD70 with cusatuzumab eliminates acute myeloid leukemia stem cells in patients treated with hypomethylating agents. Nat Med. 2020 Sep;26(9):1459-1467.

REF 14

National Cancer Institute Drug Dictionary (drug id 721679).

REF 15

Pharmacokinetic characterization of BMS-936561, an anti-CD70 antibody-drug conjugate, in preclinical animal species and prediction of its pharmacok... Biopharm Drug Dispos. 2016 Mar;37(2):93-106.

REF 16

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

REF 17

J Clin Oncol 32:5s, 2014 (suppl; abstr 2558).

REF 18

Bristol-Myers Squibb swallows last of antibody pioneers. Nat Biotechnol. 2009 Sep;27(9):781-3.

REF 19

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

REF 20

SGN-CD70A, a novel and highly potent anti-CD70 ADC, induces double-strand DNA breaks and is active in models of MDR+ renal cell carcinoma (RCC) and non-Hodgkin lymphoma (NHL). Cancer Research 10/2014; 74(19 Supplement):2647-2647.

REF 21

National Cancer Institute Drug Dictionary (drug id 660730).

REF 22

Characterization of CD8+ T-cell responses in the peripheral blood and skin injection sites of melanoma patients treated with mRNA electroporated autologous dendritic cells (TriMixDC-MEL). Biomed Res Int. 2013;2013:976383.

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