Antibody responses of remission leukemia patients receiving active specific and nonspecific immunotherapy

Granatek, C. H.; K, Ezaki; Hersh, Evan M.; Keating, Michael J.; Rasmussen, Shelley L.

doi:10.1002/1097-0142(19810115)47:2<272::aid-cncr2820470211>3.0.co;2-c

Cited by 8 publications

(2 citation statements)

References 16 publications

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“…BCG‐CWS is prepared from M. bovis BCG as an insoluble fraction of the cell wall, and consists of mycolic acids, neutral sugars such as arabinose and galactose, and peptidoglycans. ( 12 ) BCG‐CWS not only shows strong adjuvant activity to elicit immune responses to antigens, ( 13–15 ) but also has potent activity to regress tumor growth in animal models and cancer patients. ( 12,16,17 ) BCG‐CWS has been proposed to activate antigen‐presenting cells through both TLR2 and TLR4.…”

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Activation of Toll‐like receptor 2 by a novel preparation of cell wall skeleton from Mycobacterium bovis BCG Tokyo (SMP‐105) sufficiently enhances immune responses against tumors

Murata¹

2008

Cancer Science

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The cell wall skeleton of Mycobacterium bovis BCG has been investigated as an immunopotentiating adjuvant for immunotherapy of malignant tumors via Toll-like receptor (TLR) 2 and TLR4. However, due to its high molecular weight, highly complicated lipoglycan structure, and complicated purification and isolation procedure, its exact structure-activity relationship has not been well established. We have newly isolated the cell wall skeleton from M. bovis BCG Tokyo (SMP-105) and examined the binding of SMP-105 with TLR. It was revealed that highly purified SMP-105 activates the nuclear factor-kB promoter in a TLR2-dependent manner, not a TLR4-dependent manner, using a reporter gene assay system. Peritoneal exudated cells of TLR2 and MyD88 knockout mice severely reduced the induction of tumor necrosis factor-a and interleukin-6 in the presence of SMP-105, whereas cells from TLR4 knockout mice produced similar levels of cytokines to wild-type mice. Dendritic cells and macrophages accumulated in the draining lymph nodes of treated mice. When mice were administered both SMP-105 and mitomycin C-inactivated Lewis lung carcinoma cells simultaneously, interferon-g-producing cells reacting to the tumor were increased distinctly in draining lymph nodes. When C57BL/6 mice, into which splenocytes from OT-I transgenic mice had been transferred, were administered with both SMP-105 and E.G7-OVA, OVA-specific cytotoxic T lymphocytes ( A nticancer immunotherapy is an attractive alternative for the treatment of patients with inoperable cancer, without the application of radiotherapy or chemotherapy, and it is expected that the side effects experienced will be lower than with classical antitumor chemotherapeutics. Although several immunotherapeutic agents have been approved for some types of cancer patients, they are not generally accepted as reliable tools that show sufficient efficacy.(1) One reason for the insufficient results of immunotherapy is the poor immunogenecity of most tumor antigens, (2) and the lack of evidence and theoretical basis of immunotherapeutic agents for regulating the antitumor immune response. Recent progress in innate immunity, in particular the function and role of dendritic cells and Toll-like receptors (TLR), offers a great opportunity to overcome previous problems. Appropriate activation of antigen presentation enhances the immunogenecity of tumor antigens to effectively increase cellular immune responses against tumors.Toll-like receptors are pathogen-associated molecular pattern recognition receptors, and play an important role in induction of the immune response via activation of innate immunity. (3,4) TLR agonists have been shown to enhance immune responses against tumors in both animal models and clinical studies. Poly I-C is a ligand for TLR3 (5) and RIG-I. (6) Imiquimod is a ligand for TLR7 and TLR8, (7) and is approved as an immunotherapeutic drug for basal cell carcinoma. CpG DNA is a ligand for TLR9, (8) and its antitumor activity against various types of tumors has been investigated in several...

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Activation of Toll‐like receptor 2 by a novel preparation of cell wall skeleton from Mycobacterium bovis BCG Tokyo (SMP‐105) sufficiently enhances immune responses against tumors

Murata¹

2008

Cancer Science

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“…In patients with AML there are recent reports on the appearance of serum antibodies reactive with leukemic cells or leukemic membrane preparations in the course of immunotherapy that prolongs the duration of remission and survival [1,12]. Thus, the 125I-protein A-binding assay presented, in combination with assays for complement-dependent cytotoxicity and possibly antibody-dependent cellular cytotoxicity (ADCC), might have a considerable potential as a tool for analysis of the specific antibody response in patients with leukemia.…”

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A 125I-protein A-binding assay detecting antibodies to cell surface antigens

Fäldt

Ankerst

1983

Cancer Immunol Immunother

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A 125I-protein A-binding assay detecting antibodies to cell surface antigens on human blood cells was developed and evaluated using sera from multitransfused nonleukemic patients sensitized against HLA antigens. The binding assay was found to be reproducible and more sensitive than conventional HLA testing. Seven patients with acute myelogenous leukemia and two patients with acute lymphoblastic leukemia successfully treated by chemotherapy were then investigated. Sera from seven of the patients studied in partial or complete remission demonstrated significant binding to autochthonous leukemic cells obtained from bone marrow or peripheral blood. In two cases sera taken during the leukemic stage demonstrated the most pronounced binding to the patients' own leukemic cells. Sera from four patients with demonstrable significant binding to autochthonous leukemic cells failed to bind to autochthonous remission cells when both types of target cells were tested in parallel. Differences in serum concentrations of IgG, IgA, and IgM were not the cause of the demonstrated increased binding of leukemic sera to autochthonous target cells. We propose that the 125I-protein A-binding assay presented in this paper detects antibodies reacting selectively with acute leukemia cells.

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Effect of neuraminidase treatment on serum reactivity to autologous leukemic blast cells

Pfreundschuh

Dörken

Brandeis

et al. 1983

Cancer Immunol Immunother

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The sera of 35 patients with acute lymphoblastic leukemia (ALL) and acute non-lymphoblastic leukemia (ANLL) were tested for reactivity against cell surface antigens of autologous leukemic blast cells by protein A assay (PA), immune adherence assay (IA), and anti-C3 mixed hemadsorption assay (C3-MHA). Autologous serum reactivity was detectable by PA in four cases and by IA and C3-MHA in about half the patients. Autologous serum reactivity occurred more often in ALL than in ANLL. Absorption studies revealed that in one patient only the autologous reactivity was directed against a restricted antigen, which could be detected only on the individual T-ALL blast cells. All other autologous antibodies detected unspecific antigens. Neuraminidase treatment had two effects: first, it increased antibody attachment to antigens which are also present on untreated cells; secondly, after neuraminidase treatment an antigen was detectable on the cell surface which could also be demonstrated on neuraminidase-treated non-leukemic cells (e.g., erythrocytes). Neither of these two effects of neuraminidase treatment seems to be tumor-specific. Possible therapeutic effects of neuraminidase are probably caused by unspecific adjuvant effects of the enzyme.

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Antibody responses of remission leukemia patients receiving active specific and nonspecific immunotherapy

Cited by 8 publications

References 16 publications

Activation of Toll‐like receptor 2 by a novel preparation of cell wall skeleton from Mycobacterium bovis BCG Tokyo (SMP‐105) sufficiently enhances immune responses against tumors

Activation of Toll‐like receptor 2 by a novel preparation of cell wall skeleton from Mycobacterium bovis BCG Tokyo (SMP‐105) sufficiently enhances immune responses against tumors

A 125I-protein A-binding assay detecting antibodies to cell surface antigens

Effect of neuraminidase treatment on serum reactivity to autologous leukemic blast cells

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