T-cell receptor specific for SLAIN motif family member 2-derived peptide–MHC complex (TCR-SLAIN2-pMHC)

T-cell receptors (TCRs) specific for SLAIN2-derived peptide–MHC complexes are specialized immune receptors designed to recognize and bind to fragments of the SLAIN motif family member 2 (SLAIN2) protein presented by Major Histocompatibility Complex (MHC) molecules on the surface of malignant cells. SLAIN2 is a microtubule-associated protein that plays a critical role in regulating microtubule dynamics, centrosome integrity, and mesenchymal cell invasion, making it a significant driver of tumor metastasis. In certain cancers, particularly those with microsatellite instability (MSI-H), SLAIN2 can undergo frameshift mutations that generate highly immunogenic neoantigens, while in others, it is overexpressed as a tumor-associated antigen. These TCRs are primarily utilized in the development of adoptive cell therapies, such as TCR-engineered T-cell (TCR-T) therapy, where a patient's own T cells are genetically modified to express the SLAIN2-specific receptor. Upon reinfusion, these modified T cells selectively target and eliminate cancer cells presenting the SLAIN2-pMHC complex, such as the SPRGFPLGL peptide restricted to HLA-B*07:02. This therapeutic approach aims to harness the precision of the adaptive immune system to treat solid tumors and hematologic malignancies that are otherwise resistant to conventional therapies. Clinical and preclinical development focuses on ensuring high TCR affinity and specificity to maximize anti-tumor efficacy while minimizing the risk of off-target reactivity with healthy tissues.

Other names

SLAIN2-specific T-cell receptorTCR targeting SLAIN2/HLA complexSLAIN2-pMHC-specific TCR

T-cell receptors (TCRs) engineered into T cells (TCR-T therapy) recognize specific SLAIN2-derived peptides, such as the HLA-B*07:02-restricted peptide SPRGFPLGL, presented on the surface of tumor cells. This binding event triggers the formation of an immunological synapse, leading to T-cell activation, the release of cytotoxic perforins and granzymes, and the secretion of pro-inflammatory cytokines (e.g., IFN-gamma, TNF-alpha), which collectively induce apoptosis and lysis of the target cancer cell.