Leukemia-associated antigen-loaded autologous dendritic cells (LAA-DC)

Leukemia-associated antigen-loaded autologous dendritic cells are a form of cellular immunotherapy used to induce a targeted immune response against hematologic malignancies. This approach involves isolating a patient's own dendritic cells (DCs), loading them with leukemia-specific or leukemia-associated antigens (LAAs), and maturing them ex vivo [1]. These DCs then present the antigens via Major Histocompatibility Complex (MHC) class I and II molecules to T-cells [2]. Once re-administered to the patient, these professional antigen-presenting cells migrate to lymph nodes to prime CD8+ cytotoxic T-lymphocytes and CD4+ helper T-cells [3]. The resulting immune response is designed to recognize and eliminate leukemia cells, particularly in the setting of minimal residual disease (MRD) [1]. This therapeutic strategy aims to overcome the immune evasion mechanisms often employed by leukemic blasts [2]. Clinical trials have primarily focused on Acute Myeloid Leukemia (AML), where DC vaccines are used as post-remission therapy to prevent relapse [3]. The interaction between the MHC-peptide complex on the DC and the T-cell receptor (TCR) is the fundamental mechanism for initiating this anti-leukemic activity [2]. Citations: [1] Anguille, S., et al. (2012). Blood. doi:10.1182/blood-2011-08-348243. [2] Lichtenegger, F. S., et al. (2017). Journal of Clinical Medicine. doi:10.3390/jcm6010010. [3] Van de Corput, L., et al. (2021). Frontiers in Immunology. doi:10.3389/fimmu.2021.664398.

Other names

Leukemia-associated antigen-pulsed dendritic cellsDC-based leukemia vaccineAutologous dendritic cell vaccineMHC-peptide-pulsed dendritic cellsLeukemia-derived peptide-pulsed autologous dendritic cells

The mechanism involves the ex vivo loading of autologous dendritic cells with leukemia-associated antigens, which are processed and presented on MHC Class I and II molecules. Upon re-injection, these mature dendritic cells migrate to the lymph nodes where they present these antigens to naive T-cells, inducing the expansion of leukemia-specific CD8+ cytotoxic T-lymphocytes and CD4+ helper T-cells to target and kill malignant cells [1][2].