Apoptotic tumor cells are superior to tumor cell lysate, and tumor cell RNA in induction of autologous T cell response in B-CLL.
B cell chronic lymphocytic leukemia (B-CLL) is a chronic leukemia manifested by increased numbers of B cells in circulation. The slow, smouldering nature of the disease in a significant proportion of the cases makes it an ideal target for immunotherapy. Dendritic cell (DC)-based immunotherapy is emerging as an exciting modality with significant clinical potential. In this study, three strategies for delivering antigens to DC, namely apoptotic bodies (Apo-DC), tumor lysates, and tumor RNA were studied in an autologous setting. In all six CLL patients, Apo-DC induced higher HLA-restricted, T cell responses than DC pulsed with tumor lysate or RNA. Real-time PCR confirmed higher expression of genes for IL-2 and IFN-gamma in T cells stimulated with Apo-DC. Concurrently, no IL-10 and low IL-4 responses indicated that the immune response was primarily of the Th1 type. Enzyme-linked immunospot assay revealed high IFN-gamma secretion by T cells when Apo-DC was used to stimulate autologous T cells in all patients. Our data suggest that cellular vaccines with DC loaded with apoptotic bodies may be a suitable approach for immunotherapy of B-CLL.
Kokhaei
P
P
Immune and Gene Therapy Lab., CCK, Karolinska Hospital, Stockholm, Sweden.
Choudhury
A
A
Mahdian
R
R
Lundin
J
J
Moshfegh
A
A
Osterborg
A
A
Mellstedt
H
H
D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D002457:Cell Extracts / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D002457:Cell Extracts; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma