Augmentation of autologous T cell reactivity with acute myeloid leukemia (AML) blasts by Toll-like receptor (TLR) agonists.

This study investigated whether TNF-α, Toll-like receptors (TLRs) 7/8 agonist resiquimod (R848), the TLR4 agonist lipopolysaccharide (LPS) and their combinations can enhance autologous AML-reactive T cell generation in an in vitro culture. AML peripheral blood or bone marrow mononuclear cells were cultured in medium supplemented with GM-CSF/IL-4 to induce dendritic cell (DC) differentiation of AML blasts (AML-DC). The impact of TNF-α, LPS, R848 and their combinations on AML-DC cultures was analyzed.

Generation of T-cell lines to autologous acute myeloid leukemia cells by competitive limiting dilution culture of acute myeloid leukemia mononuclear cells.

Objective: To develop a novel method of generating multiple autologous acute myeloid leukemia (AML) reactive T-cell lines as a step toward adoptive immunotherapy for AML.

Materials And Methods: AML peripheral blood mononuclear cells (MNC), including >90% AML blasts and 1% to 3% T cells, were seeded in limiting dilution culture in which AML blasts were induced to undergo dendritic cell (DC) differentiation. T cells were primed and activated with the addition of a cytokine combination.

The inhibitory effect of anti-CD33 monoclonal antibodies on AML cell growth correlates with Syk and/or ZAP-70 expression.

Objectives: Acute myeloid leukemia (AML) cells express the cell surface antigen CD33 that can function as a downregulator of cell growth, mediating growth arrest and apoptosis. The protein kinase Syk is an essential element in several cascades coupling certain antigen receptors to cell responses. Recently we reported that CD33 recruits Syk for its signaling in AML cell lines.

Sequential modulation of growth factors: a novel strategy for adoptive immunotherapy of acute myeloid leukemia.

Evidence from allogeneic hematopoietic stem cell transplantation indicates a possible immune response against leukemia-associated antigens in patients with either acute myeloid leukemia (AML) or chronic myeloid leukemia (CML). However, autologous immune responses are less evident. We have developed a method using sequential modulation of growth factors (SMGF) to generate specific anti-AML T-cells from primary cultures of mononuclear cells (MNCs) from patients with AML.