Target intelligence / Profile preview

Signaling lymphocytic activation molecule family member 6 (SLAMF6) (SLAMF6)

Target
SLAMF6
Molecular classification
Receptor, Signaling lymphocytic activation molecule family, Immunoglobulin superfamily, Immune checkpoint
01

Overview

CD352, also known as Signaling Lymphocytic Activation Molecule Family Member 6 (SLAMF6) or NTB-A, is a type I transmembrane glycoprotein belonging to the signaling lymphocytic activation molecule (SLAM) family of immunomodulatory receptors [1, 3, 8]. It is constitutively expressed on various immune cells, including Natural Killer (NK) cells, T cells, and B cells, where it mediates homotypic interactions by binding to other SLAMF6 molecules [2, 3, 10]. The receptor's function is context-dependent, acting as either an activating or inhibitory signal based on the recruitment of intracellular adaptors like SAP and EAT-2 [3, 8, 12]. In oncology, CD352 is a significant therapeutic target due to its high expression on multiple myeloma and other B-cell malignancies [1, 4, 6]. Therapeutic strategies have included antibody-drug conjugates (ADCs) like SGN-CD352A, which delivers a cytotoxic payload to malignant cells, and more recently, its exploration as an immune checkpoint inhibitor to reverse T-cell exhaustion [4, 11, 13]. Beyond cancer, CD352 is implicated in autoimmune conditions like systemic lupus erythematosus and viral infections such as HIV-1 [5, 7].

Other names
CD352NTB-ANK-T-B-antigenLy108KALISF2000TCOMActivating NK receptor
02

Mechanism of action

CD352-targeted antibody-drug conjugates (ADCs) deliver cytotoxic payloads like pyrrolobenzodiazepine (PBD) dimers to induce DNA damage and apoptosis in cancer cells [1, 4]. Additionally, blocking SLAMF6 'cis' homotypic interactions on T cells acts as an immune checkpoint inhibitor, enhancing T-cell activation and anti-tumor immunity [10, 11].

03

Biological functions

Immune responseSignal transductionCell adhesionApoptosisCell proliferationNK cell activationT cell co-stimulation
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Disease associations

CancerInflammationInfectionAutoimmune disease
05

Safety considerations

Potential off-tumor toxicity due to expression on healthy B, T, and NK cells [4, 10]Toxicity associated with high-potency payloads in ADCs [4]Challenging therapeutic window [4]
06

Interacting drugs

SGN-CD352A
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Biomarkers

SLAMF6 cell surface expression [1, 4]Progenitor-exhausted T cell (Tpex) frequency [11, 14]

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