Interleukin-2 (IL-2) and IL-15 play pivotal roles in T cell activation, apoptosis, and survival, and are implicated in leukemias and autoimmune diseases.
In a phase IV trial (Re:Mission Trial, NCT01347996, http://www.clinicaltrials.gov ) 84 patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received ten consecutive 3-week cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose interleukin-2 (IL-2) to prevent relapse of leukemia in the post-consolidation phase.
Functional RNAi screen targeting cytokine and growth factor receptors reveals oncorequisite role for interleukin-2 gamma receptor in JAK3-mutation-positive leukemia.
Blockade of IL2 and IL15 using monoclonal antibodies has been reported to be of value in the treatment of patients with leukemia, autoimmune disorders, and in the prevention of allograft rejection.
To search for these molecules we aligned IL-2 regulated genes detected by Affymetrix gene expression microarrays with the STAT5 cistrome identified by chip-on-ChIP analysis in an IL-2-dependent human leukemia cell line, Kit225.
Possible explanations for these outcomes include immunologic response to sepsis by a leukemia-specific T-cell response or the release of various cytokines, such as tumor necrosis factor and interleukin-2, during infections.
We believe our results provide important mechanistic insights for the potential use of IL-2-expanded CB-derived NK cells for adoptive immune therapy in leukemia.
One agent, containing human interleukin-2 and truncated diphtheria toxin (denileukin diftitox), has been approved for use in cutaneous T-cell lymphoma, and has shown activity in other hematologic malignancies, including leukemias and lymphomas.
Earlier we have shown that interleukin-2 (IL-2)-activated MNC from cord blood have significant cytotoxic activity against human leukemia and breast cancer cells in vitro and in vivo, compared to MNC from peripheral blood.
The goal of this study was to define the potential to use canine lymphoma and leukemia as suitable models to refine therapeutic approaches targeting the interleukin-2 receptor (IL-2R).
Our results suggest that the effects of physiologically achievable concentrations of butyrate on IL-2R expression could be exploited to enhance the susceptibility of intermediate and low-affinity IL-2R expressing leukemia cells to DAB(389)IL-2.
IL-2-dependent clones established from the DN alphabeta T cell population in the PEC of IL-2 receptor alpha-chain transgenic B6 mice exhibited potent cytotoxicity against a series of B cell lineage leukemias and myelomas, such as CD5+BCL1 and MOPC, without affecting NK-susceptible targets.
The results suggest that although reduction in the proportion of leukaemia in contaminated marrow can be detected after incubation with IL-2 for 24 h, complete elimination of minimal residual disease requires longer incubation times.
Four aspects are discussed: (i) the generalized immune activation induced by the systemic administration of cytokines, in particular, interleukin-2; (ii) the specific T cell-mediated reactions against tumour cells through the recognition of tumour-associated molecules, 1) and tyrosinase proteins described in melanomas, and minor histocompatibility antigens in the setting of allogenic bone marrow transplantation for leukaemia; (iii) the potentially significant but still hypothetical immune-mediated recognition of molecules either tumour-associated or transformation-related (including altered oncogenic proteins); and (iv) the role of co-stimulatory molecules in the induction of tumour-specific immunity.
Expression of human T-cell leukaemia virus type I and associated antigens, and interleukin-2 and receptor in lymph nodes of adult T-cell leukaemia/lymphoma.
IL-1-induced production of IL-2 and IFN-gamma in subclones of human T-cell derived leukaemia HSB.2 cells: regulation by phytohaemagglutinin-mediated (poly)phosphoinositide breakdown and cyclic AMP.
These data presented the possibility that lck gene product may be one of the intervening molecules which transduce the signal from the IL-2R into the cell interior, and play an important role in the pathophysiology of adult T cell leukemia, especially in the transition of these leukemias from the IL-2-dependent stage to IL-2-independent one for their growth.
Phorbol ester induces interleukin-2 receptor on the cell surface of precursor thymocyte leukemia with no rearrangement of T cell receptor beta and gamma genes.
Monoclonal antibodies specific for the interleukin-2 receptor are being evaluated in the treatment of HTLV-I-induced leukemias and other conditions involving the inappropriate function of activated T cells.