Interleukin-2 liposome inhalation therapy is safe and effective for dogs with spontaneous pulmonary metastases

Khanna, Chand; Anderson, Peter M.; Hasz, Diane E.; Katsanis, Emmanuel; Neville, Mary E.; Klausner, Jeffrey S.

doi:10.1002/(sici)1097-0142(19970401)79:7<1409::aid-cncr19>3.0.co;2-3

Cited by 111 publications

(55 citation statements)

References 43 publications

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“…Therefore, the long-term goal of our efforts was the development of a gene delivery system that could be used clinically in an aerosol form. Aerosolization not only has the advantage of an enhanced therapeutic effect in early bronchial lesions, small metastases from other distant primaries, or diffuse forms of NSCLC like bronchoalveolar carcinoma but also offers the likely possibility of a muchdecreased systemic toxicity due to lower systemic exposure (4,5,8,10) and a higher distribution into the intrathoracic lymphatic system.…”

Section: Discussionmentioning

confidence: 99%

p53 Aerosol Formulation with Low Toxicity and High Efficiency for Early Lung Cancer Treatment

Zou

Tornos

Qiu

et al. 2007

Clinical Cancer Research

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Purpose: To develop an optimal nonviral aerosol formulation for locoregional treatment of early lung cancer. Experimental Design: The formulation was made of polylysine/protamine combination (AND) as the carrier and p53 gene (p53sm) as therapeutic agent. To estimate the aerosol deposition, the aerodynamic size of the AND-p53sm was measured with extrusion-precipitation method. To accurately determine the dose, the aerosol efficiency in mice was measured with a fluorescent dye. The transfection efficiency and DNA protection function of the aerosolized formulation in cultured cells and mouse lungs were detected with reporter gene assays and/or reverse transcription-PCR.The preclinical safety and efficacy of AND-p53sm were studied in healthy mice and mice bearing orthotopic human non^small-cell lung cancer (NSCLC) xenograft. Results: After aerosolization, AND is 3-to 17-fold more effective than commonly used PEI or cationic lipid formulations in transfecting the NSCLC cells (relative light units, 1,494 versus 534 and 86; P < 0.003). Aerodynamic size of AND-p53sm ranged 0.2 to 3 Am is the optimal aerosol droplets for deposition in the entire human respiratory tract. Significant gene expression was detected in the lungs of mice given aerosolized AND-p53sm and AND-luciferase. Aerosolized AND-p53sm significantly prolonged the life of mice bearing orthotopic human NSCLC xenografts, and it was more effective than an optimal i.v. cisplatin chemotherapy (increased life span, 93% versus 25%; P = 0.014). Inhalation of AND produced low and reversible pulmonary toxicity and no systemic toxicity. Conclusions: This optimal formulation is suitable for delivering biological materials to human lung with aerosol administration. This therapeutic strategy is an option for patients with early lung cancer and bronchoalveolar carcinoma.

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Section: Discussionmentioning

confidence: 99%

p53 Aerosol Formulation with Low Toxicity and High Efficiency for Early Lung Cancer Treatment

Zou

Tornos

Qiu

et al. 2007

Clinical Cancer Research

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“…Animal studies were carried out in dog having pulmonary metastases or primary lung tumors to show safety and efficacy of the treatment. Minimal toxicity was evidenced in dogs with administration of inhaled IL-2 liposomes twice or three times daily for 30 d. Of the nine dogs treated, two dogs with metastatic pulmonary osteosarcoma showed complete metastasis regression and one dog with lung carcinoma had long-term stabilization of disease (Khanna et al, 1997). A Phase I clinical trial designed to asses the feasibility and toxicity of IL2 liposomes administration by aerosol to patients with pulmonary metastases was conducted at the Mayo Clinic (Rochester, NY).…”

Section: Nanocarrier Formulations Administered As Liquid Aerosolsmentioning

confidence: 99%

Loco-regional administration of nanomedicines for the treatment of lung cancer

et al. 2015

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Lung cancer poses one of the most significant challenges to modern medicine, killing thousands every year. Current therapy involves surgical resection supplemented with chemotherapy and radiotherapy due to high rates of relapse. Shortcomings of currently available chemotherapy protocols include unacceptably high levels of systemic toxicity and low accumulation of drug at the tumor site. Loco-regional delivery of nanocarriers loaded with anticancer agents has the potential to significantly increase efficacy, while minimizing systemic toxicity to anticancer agents. Local drug administration at the tumor site using nanoparticulate drug delivery systems can reduce systemic toxicities observed with intravenously administered anticancer drugs. In addition, this approach presents an opportunity for sustained delivery of anticancer drug over an extended period of time. Herein, the progress in the development of locally administered nanomedicines for the treatment of lung cancer is reviewed. Administration by inhalation, intratumoral injection and means of direct in situ application are discussed, the benefits and drawbacks of each modality are explored.

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“…There were increases in white cells and effector cells in the broncho-alveolar lavage fluid of dogs treated with liposomal IL-2 but no haematological or clinical toxicity. A preclinical study in which dogs were treated with aerosols of liposomal IL-2 gave spectacular results (Khanna et al, 1997). Aerosolised liposomal IL-2 was used to treat 9 dogs, 7 with pulmonary metastases of a primary osteosarcoma and 2 with primary lung carcinomas.…”

Section: Interleukin-2 (Il-2)mentioning

confidence: 99%