In Vitro Generation of Cytotoxic CD4 Lymphocyte Response against Autologous Acute Myeloid Leukemia

Abstract

Relapsed and refractory disease shortens the survival of acute myeloid leukemia (AML) patients. Therefore, additional therapy apart from conventional chemotherapy and stem cell transplantation is urgently needed, especially in eradicating residual leukemic stem cells. The identification of leukemia associated antigens, and the observation that administration of allogeneic T cells may mediate graft versus leukemia effect paved the way to develop various immunotherapy strategies. Effective provision of both tumor antigen and co-stimulation are essential for strategies aimed at enrolling cytotoxic T- lymphocytes to eradicate leukemic cells. In this study, we attempted to up-regulate co- stimulators on leukemic cells (termed “dendritisation” to mimic dendritic cells in providing strong co-stimulation) and couple with inherent leukemic antigens to generate specific antileukemic T-lymphocytes against autologous blast cells. Our study shows evidence of distinct cytotoxicity of CD4 positive T lymphocytes against autologous blast cells. Dendritised AML blasts were able to function with antigen presenting capability, while still phenotypically existing as blast cells. This was also achievable for a wide range of subtypes of AML, making it a potential immunotherapy against AML.