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Leukemia-associated tumor antigens (presented by dendritic–leukemic cell hybrids) (LATA)

Target
LATA
Molecular classification
Antigen, Protein, Peptide
01

Overview

Leukemia-associated tumor antigens (LATAs) presented on MHC class I and II of dendritic–leukemic cell hybrids represent a collective target pool used in personalized cancer immunotherapy. This approach involves the physical fusion of a patient's own dendritic cells with their leukemic blasts to create a hybrid cell that possesses the potent antigen-presenting machinery of the dendritic cell and the full antigenic profile of the tumor (Avigan et al., 2004). These hybrids process and display a wide array of leukemia-specific peptides on both MHC class I and II molecules, allowing for the simultaneous activation of CD8+ cytotoxic T cells and CD4+ helper T cells (Rosenblatt et al., 2016). By providing essential co-stimulatory signals like CD80 and CD86, the hybrid cells overcome the immune-evasive nature of leukemic blasts, which typically lack the signals necessary to trigger a robust immune response (Koido et al., 2007). This strategy targets not just a single protein, but the entire 'antigenome' of the leukemia, including known markers like WT1 and MUC1 as well as unidentified neoantigens (Gong et al., 2000). Clinically, this target system is primarily investigated for treating acute myeloid leukemia (AML) to eliminate minimal residual disease and prevent relapse following chemotherapy or stem cell transplantation.

Other names
Tumor-associated antigensLeukemia-specific antigensDC-Leukemia fusion antigensTAAsLeukemic blast antigens
02

Mechanism of action

Induction of a broad-spectrum, polyclonal T-cell response against multiple leukemia-associated antigens through simultaneous MHC class I and II presentation and co-stimulation provided by the dendritic cell partner.

03

Biological functions

Immune responseAntigen presentationT-cell activationImmune recognition
04

Disease associations

LeukemiaAcute myeloid leukemiaChronic myeloid leukemiaHematologic malignancy
05

Safety considerations

AutoimmunityInjection site reactionsLimited persistence of immune responsePotential for graft-versus-host-like reactions in allogeneic settingsImmune evasion by tumor down-regulation of MHC
06

Interacting drugs

Dendritic cell-leukemic cell fusion vaccine

1 more in the full profile.

07

Biomarkers

MHC Class IMHC Class IIWilms tumor 1 (WT1)Mucin 1 (MUC1)CD80CD86Interferon-gamma (IFN-g) production

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