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The article presents a phase I/IIa clinical trial of immunotherapy elderly patients who has acute myeloid leukemia (AML) using dendritic cell (DC) with zoledronate and WT1 peptide. It states that the promise of DC-based immunotherapy for AML was shown from a recent report on immunotherapy using WT1 messenger Ribonuceic Acid (mRNA)-electroporated DCs. It mentions that the strengthening of vaccinations may result to an improved clinical outcome.

A letter to the editor is presented that discusses the augmentation of antitumour activity of defucosylated chimeric anti-CCR4 monoclonal antibody in severe-combined immunodeficient mouse model of adult T-cell leukaemia/lymphoma using granulocyte colony-stimulating factor.

Adult T-cell leukaemia (ATL) is a peripheral T-cell neoplasm caused by human T-cell leukaemia virus type I (HTLV-I). Several clinical observations suggest that some tumour-associated antigens in ATL may be recognised by the immune system. In this study, we performed the serological screening of an expression library to identify ATL-associated antigens by using materials from a unique ATL patient with long-term stable disease. Among five distinct genes isolated, serine/arginine protein kinase 1 ( SRPK1), which has been reported to have a restricted normal tissue distribution, was found to be overexpressed in most acute type ATL samples, but not in chronic type ATL or in normal peripheral blood mononuclear cells by real-time reverse transcription polymerase chain reaction. Interestingly, the overexpression of SRPK1 in aggressive types of ATL was more exclusively observed at the protein level than at the mRNA level. Autologous antibody to SRPK1 was confirmed in the ATL patient using Western blot analysis with plasma, but not detected in asymptomatic HTLV-I carriers or in healthy volunteers. These results indicate that SRPK1 may be useful for the development of therapeutic and diagnostic methods for patients with ATL. [ABSTRACT FROM AUTHOR]

Recently, a graft- versus-lymphoma (GVL) effect has been shown in patients allografted for mantle cell lymphoma (MCL), but the antigenic targets of this response remain unclear. We screened an MCL cDNA expression library with sera at GVL response after allogeneic haematopoietic stem cell transplantation and isolated five genes including APOBEC3B. Antibody responses to APOBEC3B were correlated with clinical response. Furthermore, APOBEC3B-specific T-cell response was induced with one of the HLA-A*0201 binding peptides. In addition, APOBEC3B mRNA appeared to be upregulated in some MCL. These findings warrant further investigation of APOBEC3B as a candidate gene eliciting an effective immune response against MCL. [ABSTRACT FROM AUTHOR]

Adult T-cell leukaemia (ATL) is caused by human T-cell leukaemia virus type I (HTLV-I). It has been suggested that cytokines play a role in the development and in the neoplastic cell growth of ATL. However, the precise mechanism involved in this process still remains unclear. Interleukin-21 (IL-21) and its receptor (IL-21R) have been recently described. In this study, we examined the expression of IL-21R and the effect of IL-21 on ATL cells. Real-time reverse transcription polymerase chain reaction showed that HTLV-I-infected cell lines and primary ATL cells expressed IL-21R mRNA. Cell surface expression of IL-21R on these cells was confirmed by flow cytometric analysis using a newly developed monoclonal antibody against human IL-21R. In contrast to the expression of IL-21R, IL-21 mRNA was scarcely detectable in these cells. Notably, IL-21 induced the proliferation of ATL-43T and ED-40515(+) cells, both of which were derived from leukaemic cell clones of ATL. Concerning the intracellular signalling pathways, IL-21 activated the phosphorylation of the signal transducers and activators of transcription (STAT)3 and STAT5. Taken together, these findings provide the first evidence that ATL cells express functional IL-21R, suggesting that it may contribute to the pathophysiology of ATL. In addition, the IL-21/IL-21R system may represent a new target for the treatment of ATL. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) play an important role in innate and adaptive immunity. There are two major populations of blood DCs, myeloid DCs (myDCs) and plasmacytoid DCs (pcDCs). pcDCs are particularly important in antiviral as well as in general host defence, as they are the principal producers of type I interferons (IFNs). In this study, we analysed myDCs and pcDCs in healthy controls, human T-cell leukaemia virus type I (HTLV-I)-infected asymptomatic carriers (ACs), and patients with adult T-cell leukaemia (ATL). ATL patients had significantly decreased number of pcDCs and myDCs compared with controls. IFN- α production by peripheral blood mononuclear cells (PBMCs) was markedly reduced in ATL patients. Purified pcDCs from ACs were found to have impaired IFN- α-producing capacity, suggesting a functional defect in pcDCs in HTLV-I-infected individuals. Interestingly, pcDCs were shown to be susceptible to HTLV-I infection. Thus, impaired IFN- α production by pcDCs may contribute to the immunodeficiency observed in ATL. Furthermore, IFN- α-producing capacity was inversely correlated with HTLV-I proviral load in PBMCs from ACs, suggesting a role for pcDCs in maintaining the carrier state. Taken together, we hypothesize that the depletion and impaired IFN- α-producing capacity of blood DCs may contribute to the immunodeficiency in ATL and/or the development of ATL. [ABSTRACT FROM AUTHOR]

Recent studies have shown that human myeloid leukaemia cells can differentiate into dendritic cell (DC)-like cells (leukaemia-DCs) when cultured with a combination of cytokines. In the present study, we examined whether the transduction of leukaemia-DCs with OX40 ligand (OX40L), a member of the tumour necrosis factor (TNF) family, resulted in augmentation of their antigen presenting activity. Bicistronic retroviral vectors expressing both human OX40L and enhanced green fluorescent protein (EGFP) or EGFP alone were generated and used for transduction. Fresh leukaemic cells from five patients with acute myeloid leukaemia (AML) were isolated and retrovirally transduced with OX40L during the culture with a combination of cytokines from stem cell factor, fms-like tyrosine kinase (Flt)-3 ligand, granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-4 (IL-4) and TNF- α. After 7 d, the majority of cells showed DC-like morphology, and expressed higher levels of CD80, CD86 and HLA-DR than fresh leukaemic cells. The transduction efficiency was 8·5–27·2%. Leukaemia-DCs transduced with OX40L elicited higher proliferative response of allogeneic CD4+ T cells than fresh leukaemic cells, non-transduced, or mock-transduced leukaemia-DCs. Co-culture of allogeneic CD4+ T cells with OX40L-transduced leukaemia-DCs was superior in the generation of interferon (IFN)- γ producing CD4+ T cells and in production of IFN- γ. Furthermore, OX40L-transduced leukaemia-DCs could elicit significant proliferative response of human leucocyte antigen-matched T cells from the donor in allogeneic stem cell transplantation. These results indicate that retroviral transduction of leukaemia-DCs with OX40L augments their antigen presenting cell activity and thus renders them more suitable for tumour vaccines or ex vivo stimulation of leukaemia-specific T cells. [ABSTRACT FROM AUTHOR]