Signaling lymphocytic activation molecule family member 3 (SLAMF3) (SLAMF3)

Signaling lymphocytic activation molecule family member 3 (SLAMF3), also known as CD229 or Ly9, is a type I transmembrane glycoprotein belonging to the SLAM family within the immunoglobulin superfamily (NIH, 2021). It is primarily expressed on hematopoietic cells, including T and B lymphocytes, natural killer (NK) cells, and thymocytes, where it functions as a self-ligand through homophilic interactions (Wikipedia, 2023). These interactions regulate lymphocyte activation, homeostasis, and cytokine production by recruiting adaptor proteins such as SLAM-associated protein (SAP) and Grb2 to its cytoplasmic immunoreceptor tyrosine-based switch motifs (ITSMs) (UniProt, 2023). SLAMF3 is highly and consistently overexpressed on malignant plasma cells and chemotherapy-resistant progenitor cells in multiple myeloma, regardless of disease stage (MDPI, 2022). This overexpression promotes tumor cell survival and proliferation via the RAS/ERK signaling pathway, making it an attractive target for immunotherapy (NIH, 2022). Experimental therapeutic approaches include CD229-targeted CAR-T cells and monoclonal antibodies, which have demonstrated potent anti-tumor activity in preclinical models (ResearchGate, 2022). However, the expression of SLAMF3 on healthy lymphocytes poses a risk of on-target off-tumor toxicity, which remains a significant therapeutic challenge (MDPI, 2021).

Other names

CD229Ly9hLy9T-lymphocyte surface antigen Ly-9Lymphocyte antigen 9

Targeted cell lysis via chimeric antigen receptor (CAR) T cells, antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and inhibition of homophilic signaling pathways.