Synergism of recombinant human interferon gamma with liposome‐encapsulated muramyl tripeptide in activation of the tumoricidal properties of human monocytes

Sone, Saburo; Tandon, Priti; Utsugi, Teruhiro; Ogawara, Mitsumasa; Shimizu, Eiji; Nii, Akihiko; Ogura, Takeshi

doi:10.1002/ijc.2910380407

Cited by 37 publications

(22 citation statements)

References 25 publications

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“…Liposome-encapsulated BRM were also far more effective than their free forms in vitro and in vivo for rendering murine macrophages tumoricidal [4,6,23]. Human blood monocytes can also respond to free and/or liposome-encapsulated lymphokines, including interferon 5' or MDP analogs, to become tumoricidal [13,26,28]. The tumor-cytotoxic properties of these activated monocytes are similar to those of tumoricidal murine macrophages [5].…”

Section: Introductionmentioning

confidence: 90%

Tumor cytotoxicity and interleukin 1 production of blood monocytes of lung cancer patients

Sone

Utsugi

Tandon

et al. 1990

Cancer Immunol Immunother

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The effects of lung cancer on the abilities of blood monocytes to produce interleukin-1 and to mediate antitumor activity were examined. The functional integrity of blood monocytes was determined by their capacity to respond in vitro to a variety of activating agents and become tumoricidal, as assessed by a radioactive release assay and ability to produce interleukin-1 in vitro. The results show that the presence of lung cancer significantly increased the number of harvested blood monocytes and that the spontaneous tumoricidal activity of these monocytes was slightly high as compared to monocytes obtained from healthy donors. The production of interleukin-1 by monocytes of healthy donors and lung cancer patients was similar. Blood monocytes obtained from lung cancer patients were less cytotoxic against allogeneic A375 melanoma cells as compared with those of healthy donors subsequent to incubation with a soluble muramyl dipeptide analog or lipopolysaccharide, but were as tumoricidal as those from healthy donors when activated with lipophilic muramyl tripeptide (MTP-PE) entrapped in multilamellar liposomes. The finding that monocytes of patients with lung cancer can respond to MTP-PE encapsulated in liposomes, recommends the use of these liposomes in therapy of human lung cancer.

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Section: Introductionmentioning

confidence: 90%

Tumor cytotoxicity and interleukin 1 production of blood monocytes of lung cancer patients

Sone

Utsugi

Tandon

et al. 1990

Cancer Immunol Immunother

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“…Then, lymphocytes and monocytes were separated from the mononuclear cell samples by centrifugal elutriation with a Hitachi SRR6Y rotor Sone et al, 1986). Nine lymphocyte-rich cell fractions were obtained at a speed of 2,000 rpm with increasing flow rates starting from 7 ml/min to 15 ml/min every 50 ml.…”

Section: Separation Of Peripheral Blood Lymphocyte Subpopulations Andmentioning

confidence: 99%

Heterogeneity of human lymphokine (IL‐2)‐activated killer (LAK) precursors and regulation of their LAK induction by blood monocytes

Sone

Inamura

Nii

et al. 1988

Intl Journal of Cancer

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Highly purified lymphocytes (greater than 99%) and monocytes (greater than 90%) were isolated by CCE from peripheral blood of healthy donors. Blood lymphocytes were separated by this CCE into 9 subpopulations. The NK activities of these lymphocyte fractions against NK-sensitive K-562 cells and their LAK activities against NK cell-resistant target (Daudi) cells were assayed promptly or after incubation of the fractions for 4 days with or without an optimal concentration of IL-2. NK and LAK activities were measured by 4-hr 51Cr-release assay. On the basis of their NK and LAK activities, these lymphocyte fractions were classified into 3 subpopulations of LAK precursors: one lacking both NK and LAK activities (Fr.2), one with moderate NK activity but low LAK activity (Fr.5), and one possessing both NK and LAK activities (Fr.8). Addition of autologous fresh monocytes to the lymphocyte cultures resulted in a significant increase in induction of LAK activity in Fr.2 and Fr.5. This up-regulation of lymphocytes in Fr. 2 and Fr.5 by monocytes was confirmed in parallel experiments by measuring the blastogenic response of the lymphocytes to IL-2. Deletion of lymphocytes in Fr. 8 of CD16+ (Leu-11+) NK cells resulted in 74% reduction in LAK induction, whereas depletion of mixtures of monocytes and lymphocytes in Fr. 2 of cells reacting with CD3+ (OKT3+) antibody resulted in a 66% reduction in LAK induction. This up-regulation of LAK cell induction from LAK precursors by monocytes was confirmed using 4 lines of human lung cancer cells as targets for LAK activity. These results clearly indicate that human monocytes may cause up-regulation of the expression of IL-2-induced LAK activity in T cells and in a subpopulation of NK cells.

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“…The multiple administration of liposomes containing specific immunomodulators has been shown to eradicate cancer metastases in several murine tumor systems [2,8,29,30,39] and in dogs with lung metastases of osteogenic sarcoma [22]. Similarly, liposomes containing the lipophilic muramyl tripeptide phosphatidylethanolamine (PtdEtn) have been shown to activate tumoricidal properties in blood monocytes of cancer patients [12,17,20,25,37,38]. Moreover, the results of phase I clinical trials indicate that at the minimum dose sufficient to produce desirable biological effects, these liposomes are well tolerated [3,20,25,40].…”

Section: Introductionmentioning

confidence: 99%

In situ activation of mouse macrophages and therapy of spontaneous renal cell cancer metastasis by liposomes containing the lipopeptide CGP 31362

Utsugi

Dinney

Killion

et al. 1991

Cancer Immunol Immunother

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We determined whether the intravenous administration of multilamellar vesicle liposomes (MLV) containing a lipopeptide analogue of a fragment from the cell wall of gram-negative bacteria (CGP 31362) can render BALB/c mouse alveolar macrophages tumoricidal in situ and reduce the incidence of spontaneous lung metastasis of syngeneic renal carcinoma (RENCA) cells. Alveolar macrophages (a) incubated in vitro with MLV containing CGP 31362 (MLV-31362) and (b) harvested from mice injected i.v. with MLV-31362 were rendered cytotoxic against the RENCA cells. Maximum cytotoxic activity of the macrophages was induced by injecting 5 mumol MLV consisting of 250 mg phospholipids and 0.5 mg CGP 31362. The single i.v. injection of 5 mumol MLV-31362 produced activation of macrophages that lasted for up to 4 days. Repeated i.v. injections of MLV-31362 produced a continuous antitumor activity in alveolar macrophages. To study the lipopeptide's effects on metastasis, we injected the left kidneys of BALB/c mice with RENCA cells. The kidney with growing tumor was resected 10 days later and, after a further 2 days, groups of mice were injected i.v. with MLV-31362 or with MLV-HBSS (twice weekly for 3 weeks). Treatment with MLV-31362 significantly decreased the median number of spontaneous lung metastases. These data demonstrate that the systemic administration of MLV-31362 can activate murine lung macrophages in situ and reduce the incidence of spontaneous RENCA lung metastases.

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Synergism of recombinant human interferon gamma with liposome‐encapsulated muramyl tripeptide in activation of the tumoricidal properties of human monocytes

Cited by 37 publications

References 25 publications

Tumor cytotoxicity and interleukin 1 production of blood monocytes of lung cancer patients

Tumor cytotoxicity and interleukin 1 production of blood monocytes of lung cancer patients

Heterogeneity of human lymphokine (IL‐2)‐activated killer (LAK) precursors and regulation of their LAK induction by blood monocytes

In situ activation of mouse macrophages and therapy of spontaneous renal cell cancer metastasis by liposomes containing the lipopeptide CGP 31362

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