ABSTRACT
As significant numbers of acute myeloid leukemia (AML) patients are still refractory to conventional therapies or experience relapse, immunotherapy using T cells expressing chimeric antigen receptors (CARs) might represent a valid treatment option. AML cells frequently overexpress the myeloid antigens CD33 and CD123, for which specific CARs can be generated. However, CD33 is also expressed on normal hematopoietic stem/progenitor cells (HSPCs), and its targeting could potentially impair normal hematopoiesis. In contrast, CD123 is widely expressed by AML, while low expression is detected on HSPCs, making it a much more attractive target. In this study we describe the in vivo efficacy and safety of using cytokine-induced killer (CIK) cells genetically modified to express anti-CD33 or anti-CD123 CAR to target AML. We show that both these modified T cells are very efficient in reducing leukemia burden in vivo, but only the anti-CD123 CAR has limited killing on normal HSPCs, thus making it a very attractive immunotherapeutic tool for AML treatment.
Subject(s)
Cytokine-Induced Killer Cells/immunology , Interleukin-3 Receptor alpha Subunit/antagonists & inhibitors , Leukemia, Myeloid, Acute/therapy , Receptors, Antigen/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Sialic Acid Binding Ig-like Lectin 3/antagonists & inhibitors , Animals , Cell Line, Tumor , Humans , Mice , Mice, SCID , T-Lymphocytes/immunologyABSTRACT
The examination of the thick drops shows malaria parasites in 20,8% of the slides in Minkama and Nalassi: 95,7% of those slides are positive for P. falciparum and 4,3% for P. malariae. The parasite rate, representing the percentage of children up to 9 years of age showing parasites in their blood, is 42,2%. Using the immunofluorescent test, antibodies are found in 43,7% of the blood samples in the study area. In the hospital, 51% of the patients with malaria are 0 to 4 years old children. The clinical symptoms observed are, in a decreasing frequency, fever, vomiting and diarrhoea, myalgia, arthralgia and asthenia, convulsions, delirious or coma. They are no obvious correlations concerning the rain-gauging data and the monthly number of malaria cases admitted at the hospital in this Cameroonian rainforest area.
