Intrapleural Recombinant IL-2 in Passive Immunotherapy for Malignant Pleural Effusion

Astoul, Philippe; Viallat, J. R.; Laurent, Jean-Claude; Brandely, M.; Boutin, C

doi:10.1378/chest.103.1.209

Cited by 85 publications

(32 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A number of investigators have translated some of these animal findings into clinical trials. Several published phase I and II clinical trials have documented mesothelioma tumor responses to intrapleural infusion of IL-2, IFN-␤, and IFN-␥ (36,(41)(42)(43)(44). Given this potential to respond to immunologic therapy, we therefore hypothesized that the neutralization of TGF-␤ could be effective for treatment of MM in terms of release from immunosuppressive environment and normalization of host immune surveillance.…”

Section: Introductionmentioning

confidence: 99%

Soluble Type II Transforming Growth Factor-β Receptor Inhibits Established Murine Malignant Mesothelioma Tumor Growth by Augmenting Host Antitumor Immunity

Suzuki

Kapoor

Cheung

et al. 2004

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Transforming growth factor (TGF)-␤ blockade has been proposed as an anticancer therapy; however, understanding which tumor patients might benefit most from such therapy is crucial. An ideal target of such inhibitory therapy might be malignant mesothelioma (MM), a highly lethal, treatment-resistant malignancy of mesothelial cells of the pleura and peritoneum that produces large amounts of TGF-␤. The purpose of this study was to explore the possible therapeutic utility of TGF-␤ blockade on MM.Experimental Design: To evaluate this hypothesis, we tested the effects of a soluble TGF-␤ type II receptor (sTGF-␤R) that specifically inhibits TGF-␤1 and TGF-␤3 in three different murine MM tumor models, AB12 and AC29 (which produce large amounts of TGF-␤) and AB1 (which does not produce TGF-␤).Results: Tumor growth of both established AB12 and AC29 tumors was inhibited by sTGF-␤R. In contrast, AB1 tumors showed little response to sTGF-␤R. The mechanism of these antitumor effects was evaluated and determined to be primarily dependent on immune-mediated responses because (a) the antitumor effects were markedly diminished in severe combined immunodeficient mice or mice depleted of CD8 ؉ T cells and (b) CD8 ؉ T cells isolated from spleens of mice treated with sTGF-␤R showed strong antitumor cytolytic effects, whereas CD8 ؉ T cells isolated from spleens of tumor-bearing mice treated with of control IgG2a showed no antitumor cytolytic effects.Conclusions: Our data suggest that TGF-␤ blockade of established TGF-␤-secreting MM should be explored as a promising strategy to treat patients with MM and other tumors that produce TGF-␤.

show abstract

Section: Introductionmentioning

confidence: 99%

Soluble Type II Transforming Growth Factor-β Receptor Inhibits Established Murine Malignant Mesothelioma Tumor Growth by Augmenting Host Antitumor Immunity

Suzuki

Kapoor

Cheung

et al. 2004

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…As far as pleural and lung tumours are concerned, tumour transplantation has generally been carried out by s.c. injection of neoplastic cells in immunodeficient mice, or to perfect a more relevant model of mesothelioma, in the peritoneal cavity of mice (Smythe et al, 1994;Hwang et al, 1995). More recently, orthotopic implantation by injection via thoracotomy (Astoul et al, 1993;Esandi et al, 1997) has been developed providing a relevant model of pleural mesothelioma. However, thoracotomy is invariably associated with trauma to the pleural cells and subpleural tissue then followed by processes of inflammation and tissue repair.…”

Section: Discussionmentioning

confidence: 99%

“…According to Chahinian et al (1991), xenografts in nude mice are relevant models to investigate a therapeutical potency in specific tumours. To improve the relevance of these methods, orthotopic transplantations have been performed (Astoul et al, 1993;Togo et al, 1995).…”

mentioning

confidence: 99%

“…In addition to s.c. implantation, several other models have been employed including pleural grafts in immunodeficient mice or rats, and intraperitoneal (i.p.) injection of tumour cells (Astoul et al, 1993;Smythe et al, 1994;Esandi et al, 1997). However, tumour implantation through surgery entails inflammatory reactions, scarring and local fibrosis that may interfere with tumour evolution.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Pleuro-pulmonary tumours detected by clinical and chest X-ray analyses in rats transplanted with mesothelioma cells

et al. 1999

View full text Add to dashboard Cite

Summary New strategies for cancer therapy must be developed, especially in severe neoplasms such as malignant pleural mesothelioma. Animal models of cancer, as close as possible to the human situation, are needed to investigate novel therapeutical approaches. Orthotopic transplantation of cancer cells is then relevant and efforts should be made to follow up tumour evolution in animals. In the present study, we developed a method for the orthotopic growth of mesothelioma cells in the pleural cavity of Fischer 344 and nude rats, along with a procedure for clinical survey. Two mesothelioma cell lines, of rat and human origin, were inoculated by transthoracic puncture. Body weight determination and chest X-ray analyses permitted the follow-up of tumour evolution by identifying different stages. Autopsies showed that tumours localized on the whole pleural cavity (diaphragm, parietal pleura), mediastinum and pericardium. Tumour morphology and antigenic characteristics were consistent with those of the inoculated cells and were similar in both types of rats inoculated with the same cell type. These results demonstrate that mesothelioma formation in rats can be followed up by clinical and radiographic survey after gentle intrathoracic inoculation of mesothelioma cells, thus allowing the definition of stages of interest for further experimental trials.

show abstract

“…Im frühen Stadium I wurden unter Interferon−ã, intrapleural gegeben z. T. lange Überlebenszeiten beobachtet [77]. Letztlich konnte sich die intrapleurale Therapie mit Inter− leukin [77,78] Serie: ¹Pleuraerkrankungen" (6) war. In den Stadien III und IV ist aber offenbar eine zusätzliche systemische Therapie notwendig.…”

Section: Key Pointsunclassified

Therapeutische Optionen beim malignen Pleuramesotheliom

Serke

Loddenkemper²

2005

Pneumologie

View full text Add to dashboard Cite

Malignant pleural mesothelioma may be treated with surgery, radiotherapy and chemotherapy. In most patients, the treatment remains palliative with symptom relief and a moderate survival gain. Only a minority of patients with early stage mesothelioma may be cured by a multimodal approach including radical surge− ry, chemotherapy, and radiotherapy. We discuss the role of sur− gery with either radical extrapleural pleuropneumonectomy or less invasive palliative pleurectomy and decortication, and the role of radiotherapy, in which the main problem is how to deliver sufficient doses to the pleural surface, sparing radiosensitive structures such as the lung, heart, liver, and kidneys. Chemothe− rapeutic options are discussed with older' mono− and combina− tion regimens and the new promising combination cisplatinum/ pemetrexed, now the standard regimen' for malignant pleural mesothelioma. Experimental approaches such as hyperthermia, interferons or interleukins, and small molecules' or antibodies inhibiting the EGFR oder VEGF receptor are under clinical evalua− tion. For the majoritiy of our patients we recommend talcum pleurodesis either by medical thoracoscopy or VATS, followed by chemotherapy with platinum/pemetrexed. Radiotherapy may be applied in case of local tumour growth. The individual therapeutic decision will depend on tumour stage, concomitant diseases, performance status, and on the patient's preference.

show abstract

Intrapleural Recombinant IL-2 in Passive Immunotherapy for Malignant Pleural Effusion

Cited by 85 publications

References 30 publications

Soluble Type II Transforming Growth Factor-β Receptor Inhibits Established Murine Malignant Mesothelioma Tumor Growth by Augmenting Host Antitumor Immunity

Soluble Type II Transforming Growth Factor-β Receptor Inhibits Established Murine Malignant Mesothelioma Tumor Growth by Augmenting Host Antitumor Immunity

Pleuro-pulmonary tumours detected by clinical and chest X-ray analyses in rats transplanted with mesothelioma cells

Therapeutische Optionen beim malignen Pleuramesotheliom

Contact Info

Product

Resources

About