picibanil and Leukemia

Topics: Animals; Antibodies, Monoclonal; BCG Vaccine; Brain Neoplasms; Cell Fusion; Glioma; Humans; Hybridomas; Immunotherapy; Interferon Inducers; Interferons; Leukemia; Levamisole; Lymphoma; Mice; Mice, Inbred BALB C; Picibanil

The prognosis for elderly patients with acute myeloid leukemia (AML) remains dismal. To explore the potential of immunotherapy for improving clinical outcomes for these patients, we performed a phase I clinical trial of dendritic cell (DC)-based immunotherapy for elderly patients with AML.. Autologus monocytes were obtained after reducing tumor burden by chemotherapy. Immature DCs induced with granulocyte-macrophage colony-stimulating factor and interleukin-4 were pulsed with autologous apoptotic leukemic cells as antigens. DCs were administered intradermally to four patients five times at 2-week intervals. To facilitate DC migration to lymph nodes, injection sites were pretreated with killed Streptococcus pyogenes OK-432 one day before. DCs were coinjected with OK-432 to induce maturation and interleukin-12 production in vivo.. Antileukemic responses were observed by an interferon-γ enzyme-linked immunospot assay or a tetramer assay in two of four patients. In a human leukocyte antigen-A∗2402-positive patient, induction of CD8(+) T-cell responses to WT1- and human telomerase reverse transcriptase - derived peptides were observed, indicating cross-priming in vivo. The two patients with antileukemic immunity showed longer periods of disease stabilization than the other two patients.. This study demonstrates the immunogenicity of autologous DCs that cross-present leukemia-associated antigens from autologous apoptotic leukemic cells in vivo in elderly patients with AML.

Topics: Acute Disease; Aged; Apoptosis; CD8-Positive T-Lymphocytes; Cross-Priming; Dendritic Cells; Female; Fever; Flow Cytometry; Humans; Immunotherapy; K562 Cells; Leukemia; Leukemia, Myeloid; Male; Picibanil; Time Factors; Treatment Outcome

Topics: Biological Factors; Biological Products; Cytokines; Cytotoxicity, Immunologic; Humans; Immunologic Factors; Leukemia; Lymphocytes; Picibanil

Lymphocytes from peripheral blood (PBL) and from pleural effusions (PEL) of cancer patients were tested for cytotoxicity against tumor cells freshly isolated from carcinomatous pleural effusion of the same patient. Significant lysis of autologous tumor cells was recorded for 4 of 28 PBL samples and for 5 of 28 PEL cases when investigated in a 4-hour 51Cr release assay. In vitro treatment of lymphocytes for 20 hours with the streptococcal preparation OK432 resulted in an induction or augmentation of cytotoxicity against autologous tumor cells in 21 of 28 PBL and PEL specimens. OK432-induced cytotoxicity required active cell metabolism, RNA and protein syntheses, but not DNA synthesis of lymphocytes. Supernatants of OK432-stimulated lymphocytes, and interferon and interleukin 2 failed to induce autologous tumor killing. Nylon wool-nonadherent lymphocytes were involved in both spontaneous and OK432-induced lysis of fresh autologous tumor cells. OK432-activated lymphocytes from normal donors and cancer patients caused lysis of fresh allogeneic tumor cells and also K562 cells.

Topics: Adenocarcinoma; Adult; Aged; Biological Products; Cytotoxicity, Immunologic; Dactinomycin; Female; Humans; Killer Cells, Natural; Leukemia; Lung Neoplasms; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Mitomycin; Mitomycins; Picibanil; Pleural Effusion