Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTNCIE0)

• DTT Name: CD70 antigen (CD27-L)
• Synonyms: Tumor necrosis factor ligandsuperfamily member 7; Tumor necrosis factor ligand superfamily member 7; TNFSF7; CD27LG; CD27L; CD27 ligand
• Gene Name: CD70
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Cytokine: tumor necrosis factor
• UniProt ID: CD70_HUMAN
• TTD ID: T67805
• Sequence:
  MPEEGSGCSVRRRPYGCVLRAALVPLVAGLVICLVVCIQRFAQAQQQLPLESLGWDVAEL
  QLNHTGPQQDPRLYWQGGPALGRSFLHGPELDKGQLRIHRDGIYMVHIQVTLAICSSTTA
  SRHHPTTLAVGICSPASRSISLLRLSFHQGCTIASQRLTPLARGDTLCTNLTGTLLPSRN
  TDETFFGVQWVRP
• 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.
• KEGG Pathway: Cytokine-cytokine receptor interaction (hsa04060)
• Reactome Pathway: TNFs bind their physiological receptors (R-HSA-5669034)

Molecular Interaction Atlas (MIA) of This DTT

11 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
JNJ-74494550	DM3ICO6	Myelodysplastic syndrome	2A37	Phase 2	[2]
4SCAR19 and 4SCAR70	DMKC8F9	B-cell lymphoma	2A86	Phase 1/2	[1]
AMG 172	DMS72GN	Renal cell carcinoma	2C90	Phase 1	[3]
Anti-hCD70 CAR transduced PBL	DMK4GIS	Ovarian cancer	2C73	Phase 1	[4]
BMS-936561	DMYIBFM	Haematological malignancy	2B33.Y	Phase 1	[5]
CTX130	DM926CH	T-cell lymphoma	2A90	Phase 1	[6]
MDX-1203	DM0RIQF	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
MDX-1411	DM3402P	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
SEA-CD70	DMX94YF	Acute myeloid leukaemia	2A60	Phase 1	[9]
SGN-70	DMXA7W9	Autoimmune diabetes	5A10	Phase 1	[10]
SGN-CD70A	DMMJ1PO	Non-hodgkin lymphoma	2B33.5	Phase 1	[11]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Vorsetuzumab mafodotin	DMATEL0	Renal cell carcinoma	2C90	Discontinued in Phase 1	[12]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
TriMixDC	DML3OYH	Melanoma	2C30	Investigative	[13]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Renal cancer	2C82	Kidney	1.53E-09	0.76	2.84
Melanoma	2C82	Skin	7.44E-01	-0.18	-0.43

References

• [1] ClinicalTrials.gov (NCT03125577) Combination CAR-T Cell Therapy Targeting Hematological Malignancies
• [2] Targeting CD70 with cusatuzumab eliminates acute myeloid leukemia stem cells in patients treated with hypomethylating agents. Nat Med. 2020 Sep;26(9):1459-1467.
• [3] National Cancer Institute Drug Dictionary (drug id 721679).
• [4] ClinicalTrials.gov (NCT02830724) Administering Peripheral Blood Lymphocytes Transduced With a CD70-Binding Chimeric Antigen Receptor to People With CD70 Expressing Cancers
• [5] 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.
• [6] Clinical pipeline report, company report or official report of CRISPR Therapeutics.
• [7] J Clin Oncol 32:5s, 2014 (suppl; abstr 2558).
• [8] Bristol-Myers Squibb swallows last of antibody pioneers. Nat Biotechnol. 2009 Sep;27(9):781-3.
• [9] Clinical pipeline report, company report or official report of Seagen.
• [10] 2011 Pipeline of Seattle Genetics.
• [11] 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.
• [12] National Cancer Institute Drug Dictionary (drug id 660730).
• [13] 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.