The Effect of Monophosphoryl Lipid A on Maturation of DCs from Patients with Acute Myeloid Leukaemia.
BACKGROUND
Generation of monocyte-derived dendritic cells (MDDC) is induced in the presence of GM-CSF and IL-4, and a maturation stimulus is added to the monocyte culture to obtain mature Dendritic Cells (DCs) suitable for therapy. TNF-α is the most common cytokine used for activating DCs and generating mature MDDC either alone or in combination with other cytokines.


OBJECTIVE
To compare effects of traditional cytokine cocktail (TNF-α + IL-1β) versus TLR4-agonist monophosphoryl lipid A on the viability, phenotype, cytokine profile and functionality of MDDC.


METHODS
The study included 32 individuals; twenty Acute Myeloid Leukaemia (AML) cases in complete remission and 12 healthy volunteers. They were divided into 3 groups: Group 1: control group: 12 subjects to measure the baseline levels of all markers in the monocytic preparation. Group 2: cytokine cocktail (TNF-α) group, which included 10 AML subjects. Group 3: MPLA group which included 10 AML subjects.


RESULTS
TNF-α group showed higher expression of CD83 than MPLA group indicating higher capacity to induce DC maturation but both were similar in CD86, CCR7 and IL-10 expression. Preparation of dendritic cells from AML cases in remission and loading them with tumor peptides was successful.


CONCLUSIONS
MPLA effect in DC maturation is comparable with traditional DC maturation cocktail.
Clinical Haematology Unit, Internal Medicine Department, Kasr Al Aini Faculty of Medicine, Cairo University, Cairo.
Noha Mohamed
NM
El Husseiny
Walaa Abd
WA
El Fattah Attya Elkak
Mervat Said
MS
El Ansary
Engy Mohamed Abd
EM
El Aziz El Khateeb
Mervat Wagih
MW
Mattar
Doaa Mohamed
DM
El Demerdash
D000951:Antigens, Neoplasm / Q000276:immunology; D051940:B7-2 Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D016753:Interleukin-10; D053583:Interleukin-1beta / Q000276:immunology; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000628:therapy*; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D010446:Peptide Fragments / Q000276:immunology; D054400:Receptors, CCR7 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000819:agonists*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000951:Antigens, Neoplasm; D051940:B7-2 Antigen; C515370:CCR7 protein, human; C508609:IL10 protein, human; D053583:Interleukin-1beta; D008050:Lipid A; D010446:Peptide Fragments; D054400:Receptors, CCR7; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C048436:monophosphoryl lipid A