Control of the antitumoral activity of human macrophages produced in large amounts in view of adoptive transfer

Dumont, Serge; Hartmann, Dominique; Poindron, Philippe; Oberling, F.; Faradji, A.; Bartholeyns, Jacques

doi:10.1016/0277-5379(88)90069-7

Cited by 43 publications

(16 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Macrophages inhibited by 20% the uptake of [3H]thymidine by the U937 tumour cells while rhuIFN 7 at concentrations of up to 500 U/ml, when added to the macrophages, increased their cytotoxic effect to 80% inhibition of [3H]thymidine uptake by tumour cells. This inhibition of thymidine incorporation was well correlated with loss of tumour cell viability, as assessed by the trypan blue exclusion test, in accordance with previous studies [6]. MAK cell cytotoxicity was variable from patient to patient, and from dose to dose in the same patient but not as a function of the length of treatment (Fig.…”

Section: Preparation Of Ex-vivo-activated Cytotoxic Macrophagessupporting

confidence: 81%

“…In a previous report we demonstrated that activated macrophages generated by culturing cancer patients' blood monocytes with rhuIFN 7 produced marked selective lysis of experimental and human cancer cells in vitro [6]. The [2].…”

Section: Discussionmentioning

confidence: 98%

“…The assay was a standard 24-h [3H]thymidine incorporation cytostasis assay using the tumour cell line U937 as target. Cytostasis effects were expressed as the percentage inhibition of [3H]thymidine incorporation by the treated tumour cells compared to the control tumour cells as previously reported [6]. The cytostasis effects…”

Section: Patient Characteristicsmentioning

confidence: 99%

“…Monocyte and macrophage ability for phagocytosis was determined by using yeast particles as previously published [6]. Cell suspensions (1 ml) with a density of 5 x 105 cells/ml were incubated for 2 h in petri culture dishes.…”

Section: Phagocytosismentioning

confidence: 99%

See 3 more Smart Citations

Phase I trial of intravenous infusion of ex-vivo-activated autologous blood-derived macrophages in patients with non-small-cell lung cancer: Toxicity and immunomodulatory effects

Faradji

Bohbot

Schmitt-Goguel

et al. 1991

Cancer Immunol Immunother

View full text Add to dashboard Cite

The purpose of this phase I study was to evaluate the toxicity and biological activity of autologous blood-derived macrophages activated ex-vivo with recombinant human interferon gamma (rhuIFN gamma) [monokine-activated killer (MAK) cells] and administered intravenously to 11 lung cancer patients once a week for 6 consecutive weeks. Peripheral blood monocytes were collected by leukapheresis and then purified by counterflow elutriation. The MAK cells were generated by culturing the purified monocytes in Teflon bags for 7 days and adding rhuIFN gamma to the cultured cells for the last 18 h. These MAK cells expressed differentiation-associated surface antigen MAX1, and were cytotoxic in vitro against tumour cell line U937. The MAK cells were infused at dose levels from 1 x 10(7) to 5 x 10(8) on an intrapatient dose-escalating schedule. No severe adverse side-effects occurred. Toxicity was mild to moderate [primarly fever (75%) and chills (32%)], non-dose-dependent, and non-cumulative. No consistent change in haemostatic function, or liver or renal function was observed. Dose-limiting toxicity was not reached at 5 x 10(8) cells (optimal dose reproduced for each patient). The maximum tolerated dose was not determined. The immunomodulatory activity of i.v. infused MAK cells was demonstrated both in vivo by significant increases in granulocyte count and neopterin level in the patients' peripheral blood post-infusion and in vitro by secretory products (IL-1. TNF alpha, neopterin, and thromboplastin-like substance) in the culture supernatants. The in vivo traffic patterns of autologous MAK cells labelled ex-vivo with 111In oxine were studied in 7 patients. Gamma imaging showed an immediate but transient lung uptake (less than 24 h), and a progressive uptake of radioactivity in the liver and spleen was seen from 6 h to 72 h post-infusion. Our results indicate that the preparation of high numbers of autologous, blood-derived MAK cells is a feasible procedure, and their transfusion is safe for patients. This immunotherapeutic approach seems to be encouraging from the point of view of establishing an adjuvant therapeutic modality in cancer patients with minimal residual disease.

show abstract

Section: Preparation Of Ex-vivo-activated Cytotoxic Macrophagessupporting

confidence: 81%

Section: Discussionmentioning

confidence: 98%

Section: Patient Characteristicsmentioning

confidence: 99%

Section: Phagocytosismentioning

confidence: 99%

See 2 more Smart Citations

Phase I trial of intravenous infusion of ex-vivo-activated autologous blood-derived macrophages in patients with non-small-cell lung cancer: Toxicity and immunomodulatory effects

Faradji

Bohbot

Schmitt-Goguel

et al. 1991

Cancer Immunol Immunother

View full text Add to dashboard Cite

show abstract

“…Their antitumor potential is often more efficient than other kinds of immunocompetent cells (Dumont et al 1985). In fact, these cells play a complex role in tumor biology; their presence within a tumor can either correlate with tumor destruction or tumor growth.…”

Section: Discussionmentioning

confidence: 99%

Investigation of immunomodulatory and anti-inflammatory effects of eriodictyol through its cellular anti-oxidant activity

Mokdad-Bzéouich

Mustapha

Sassi

et al. 2016

Cell Stress and Chaperones

View full text Add to dashboard Cite

Many studies have been performed to assess the potential utility of natural products as immunomodulatory agents to enhance host responses against infection or to ameliorate immune-based pathologies. To determine whether eriodictyol has immunomodulatory effects and clarify which types of immune effector cells are stimulated in vitro, we investigated the stimulatory effect of eriodictyol on spleen cells isolated from BALB/c mice. Eriodictyol significantly stimulated splenocyte proliferation. However, only B lymphocytes (not T lymphocytes) could be stimulated by eriodictyol in a dose-related manner. Studies assessing potential effect of eriodictyol on innate immunity reported that eriodictyol enhanced significantly the killing activity of natural killer (NK) cells, T lymphocytes, and macrophages. We also demonstrated that eriodictyol inhibited nitric oxide (NO) production and lysosomal enzyme activity in murine peritoneal macrophages cultured ex-vivo, suggesting a potential anti-inflammatory effect in situ. Eriodictyol revealed also a cellular anti-oxidant activity in splenocytes and macrophages. Furthermore, eriodictyol increased catalase activity in spleen cells. From this data, it can be concluded that eriodictyol exhibited an immunomodulatory effect that could be ascribed in part to a cytoprotective effect related to its anti-oxidant activity.

show abstract

Mechanism for the recruitment of macrophages to cancer site. In vivo concentration gradient of monocyte chemotactic activity

Martinet

Beck

Bernard

et al. 1992

Cancer

View full text Add to dashboard Cite

Background. Tumor stroma is characterized by the development of new blood vessels, a n inflammatory cell infiltration, and a fibrotic reaction. The inflammatory component of tumor stroma plays an important role in the modulation of tumor expansion. In this respect, macrophages constitute a major part of the inflammatory cell infiltration and can exert cytotoxic activity against tumor cells. The accumulation of macrophages in the vicinity of the tumor suggests their recruitment from circulating blood monocytes through the local release of chemotactic factors for monocytes. To detect the existence of a concentration gradient of monocyte chemotactic activity (MCA) between the tumor vicinity and blood vessels, malignant pleural effusions defined by the local presence of cancer cells were evaluated for quantification of MCA. Results. Unlike nonmalignant pleural effusions, malignant pleural effusions were characterized by the presence of increased levels of MCA, and in lung adenocarcinoma (a cancer with high inflammatory cell infiltration), pleural levels of MCA were significantly greater than in small cell lung carcinoma (a cancer with low inflammatory cell reaction). An MCA concentration gradient between pleural fluid and plasma was present in malignant effusions because pleural MCA levels in all cancer types were significantly greater than MCA levels in the plasma of the same patients. Thus, an increased local level of MCA is a feature of cancers with high inflammatory cell infiltration, and the presence of an in vivo concentration gradient of MCA suggests the direct role of this biologic activity in recruiting blood monocytes to the cancer site. Cancer 1992; 70:854-860. Methods. Conclusions.

show abstract

Control of the antitumoral activity of human macrophages produced in large amounts in view of adoptive transfer

Cited by 43 publications

References 19 publications

Phase I trial of intravenous infusion of ex-vivo-activated autologous blood-derived macrophages in patients with non-small-cell lung cancer: Toxicity and immunomodulatory effects

Phase I trial of intravenous infusion of ex-vivo-activated autologous blood-derived macrophages in patients with non-small-cell lung cancer: Toxicity and immunomodulatory effects

Investigation of immunomodulatory and anti-inflammatory effects of eriodictyol through its cellular anti-oxidant activity

Mechanism for the recruitment of macrophages to cancer site. In vivo concentration gradient of monocyte chemotactic activity

Contact Info

Product

Resources

About