Leukemia-associated antigens (BCR-ABL, WT1, and Myeloblastin) presented on dendritic cells (LAA-DC vaccine)

This target represents a multi-antigen immunotherapy approach for myeloid leukemias, specifically Chronic Myeloid Leukemia (CML) and Acute Myeloid Leukemia (AML). It involves the presentation of three key leukemia-associated antigens (LAAs)—the BCR-ABL fusion protein, Wilms Tumor 1 (WT1), and myeloblastin (Proteinase 3)—as peptide-MHC complexes on the surface of autologous dendritic cells (Maslak et al., 2008, PubMed: 18042247). BCR-ABL is a constitutively active tyrosine kinase resulting from the Philadelphia chromosome translocation, serving as a tumor-specific neoantigen (NCI Dictionary, 2024). WT1 is a zinc-finger transcription factor (UniProt: P19544), and myeloblastin is a serine protease (UniProt: P24158); both are overexpressed in leukemic blasts and play roles in cell proliferation and differentiation. By utilizing dendritic cells as professional antigen-presenting cells, this strategy aims to overcome immune tolerance and prime the patient's own T-lymphocytes to recognize and eliminate residual leukemic cells (Bocchia et al., 2005, Lancet Oncology). This therapeutic approach is typically investigated as a vaccine to maintain molecular remission or treat minimal residual disease in patients who have achieved a response to standard therapies like tyrosine kinase inhibitors.

Other names

BCR-ABL/WT1/PR3-pulsed dendritic cellsMulti-antigen DC vaccineMyeloid leukemia-associated antigensCML-DC vaccine

Active immunotherapy involving the expansion of antigen-specific CD8+ cytotoxic T-lymphocytes and CD4+ helper T-cells through the presentation of leukemia-associated antigen peptides (BCR-ABL, WT1, and myeloblastin) by autologous dendritic cells via MHC Class I and II molecules.