Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT7ILZ1)

• DTT Name: SLAM family member 7 SLAMF7 (CS1)
• Synonyms: UNQ576/PRO1138; SLAM family member 7; Protein 19A; Novel Ly9; Membrane protein FOAP-12; CRACC; CD319; CD2-like receptor-activating cytotoxic cells; CD2 subset 1
• Gene Name: SLAMF7
• DTT Type: Successful target; [1]
• BioChemical Class: Immunoglobulin
• UniProt ID: SLAF7_HUMAN
• TTD ID: T98052
• Sequence:
  MAGSPTCLTLIYILWQLTGSAASGPVKELVGSVGGAVTFPLKSKVKQVDSIVWTFNTTPL
  VTIQPEGGTIIVTQNRNRERVDFPDGGYSLKLSKLKKNDSGIYYVGIYSSSLQQPSTQEY
  VLHVYEHLSKPKVTMGLQSNKNGTCVTNLTCCMEHGEEDVIYTWKALGQAANESHNGSIL
  PISWRWGESDMTFICVARNPVSRNFSSPILARKLCEGAADDPDSSMVLLCLLLVPLLLSL
  FVLGLFLWFLKRERQEEYIEEKKRVDICRETPNICPHSGENTEYDTIPHTNRTILKEDPA
  NTVYSTVEIPKKMENPHSLLTMPDTPRLFAYENVI
• Function: SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. Isoform 1 mediates NK cell activation through a SH2D1A-independent extracellular signal-regulated ERK-mediated pathway. Positively regulates NK cell functions by a mechanism dependent on phosphorylated SH2D1B. Downstream signaling implicates PLCG1, PLCG2 and PI3K. In addition to heterotypic NK cells-target cells interactions also homotypic interactions between NK cells may contribute to activation. However, in the absence of SH2D1B, inhibits NK cell function. Acts also inhibitory in T-cells. May play a role in lymphocyte adhesion. In LPS-activated monocytes negatively regulates production of proinflammatory cytokines. Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family.
• Reactome Pathway: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Elotuzumab	DMEYHG9	Multiple myeloma	2A83	Approved	[1]

6 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PVX-410	DM6DK9A	Multiple myeloma	2A83	Phase 2	[1]
ABBV-838	DMZM0T8	Multiple myeloma	2A83	Phase 1	[2]
BCMA-CS1 cCAR	DMEPHMR	Multiple myeloma	2A83	Phase 1	[3]
CS1-CAR T Therapy	DMU8OCN	Plasma cell myeloma	2A83.1	Phase 1	[4]
MB-104	DMRP4BM	Multiple myeloma	2A83	Phase 1	[5]
UCARTCS1	DM2Y4D7	Multiple myeloma	2A83	Phase 1	[6]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Multiple myeloma	2C82	Bone marrow	9.74E-01	0.13	0.31

References

• [1] Market watch: Upcoming catalysts in Q2 2015. Nat Rev Drug Discov. 2015 Apr;14(4):228.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] ClinicalTrials.gov (NCT04156269) BCMA-CS1 Compound CAR (cCAR) T Cells for Relapsed/Refractory Multiple Myeloma. U.S. National Institutes of Health.
• [4] ClinicalTrials.gov (NCT03710421) CS1-CAR T Therapy Following Chemotherapy in Treating Patients With Relapsed or Refractory Multiple Myeloma
• [5] Clinical pipeline report, company report or official report of Mustang Bio.
• [6] ClinicalTrials.gov (NCT04142619) Study Evaluating Safety and Efficacy of UCART Targeting CS1 in Patients With Relapsed/Refractory Multiple Myeloma (MELANI-01). U.S. National Institutes of Health.