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

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

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

BACKGROUND. Systemic in vivo toxicity of interleukin-2 (IL-2) has been problematic. Antineoplastic activity of IL-2 has been modest. The authors have previously demonstrated the biologic activity and safety of aerosols of IL-2 liposomes in normal dogs. They now report objective regression of naturally occurring pulmonary metastases in dogs after 1 month of nebulized IL-2 liposome therapy. METHODS. Dogs with pulmonary metastases (n = 7) and primary lung carcinoma (n = 2) were treated with aerosols of IL-2 liposomes. Response to therapy was monitored with serial chest radiographs. Effector populations, collected by bronchoalveolar lavage (BAL) and from heparinized whole blood, were assessed for cell type, immunophenotype, and tumor cytolytic activity. Immunogenicity of human IL-2 and human serum albumin (HSA) in dogs was assessed by immunofluorescence assay. RESULTS. Two of four dogs with metastatic pulmonary osteosarcoma had complete regression of metastases; the regression remained stable for more than 12 and more than 20 months, respectively. One of two dogs with lung carcinoma had stabilization of disease for more than 8 months; the other had disease progression. Toxicity was minimal. BAL cell numbers increased more than fourfold (P = 0.01) and included significantly greater proportions and total numbers of eosinophils (P = 0.006) and lymphocytes (P = 0.008). Mean BAL effector lytic activity was significantly greater after 15 days of IL-2 liposome inhalation compared with pretreatment activity (P = 0.01); however, mean BAL lytic activity decreased after 30 days and was no longer significantly greater than pretreatment BAL lytic activity. No allergic reactions were associated with inhaled IL-2 liposome therapy. Canine antibodies against human IL-2 and HSA were detected in all dogs. CONCLUSIONS. Pet dogs with naturally occurring pulmonary metastases and primary lung carcinomas accepted inhalation treatments easily. Nontoxic and effective treatment of pulmonary metastases of osteosarcoma is possible with nebulized IL-2 liposomes.

Original languageEnglish (US)
Pages (from-to)1409-1421
Number of pages13
JournalCancer
Volume79
Issue number7
DOIs
StatePublished - Apr 1 1997
Externally publishedYes

Fingerprint

Respiratory Therapy
Liposomes
Interleukin-2
Dogs
Neoplasm Metastasis
Lung
Bronchoalveolar Lavage
Osteosarcoma
Aerosols
Carcinoma
Serum Albumin
Inhalation
Therapeutics
Pets
Eosinophils
Antineoplastic Agents
Fluorescent Antibody Technique
Disease Progression
Canidae
Hypersensitivity

Keywords

  • dogs
  • inhalation
  • interleukin-2
  • liposome
  • lung carcinoma
  • pulmonary metastases

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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; Klausner, Jeffrey S.

In: Cancer, Vol. 79, No. 7, 01.04.1997, p. 1409-1421.

Research output: Contribution to journalArticle

Khanna, Chand ; Anderson, Peter M. ; Hasz, Diane E. ; Katsanis, Emmanuel ; Neville, Mary ; Klausner, Jeffrey S. / Interleukin-2 liposome inhalation therapy is safe and effective for dogs with spontaneous pulmonary metastases. In: Cancer. 1997 ; Vol. 79, No. 7. pp. 1409-1421.
@article{10e153423f2842a098c4c604bef4df02,
title = "Interleukin-2 liposome inhalation therapy is safe and effective for dogs with spontaneous pulmonary metastases",
abstract = "BACKGROUND. Systemic in vivo toxicity of interleukin-2 (IL-2) has been problematic. Antineoplastic activity of IL-2 has been modest. The authors have previously demonstrated the biologic activity and safety of aerosols of IL-2 liposomes in normal dogs. They now report objective regression of naturally occurring pulmonary metastases in dogs after 1 month of nebulized IL-2 liposome therapy. METHODS. Dogs with pulmonary metastases (n = 7) and primary lung carcinoma (n = 2) were treated with aerosols of IL-2 liposomes. Response to therapy was monitored with serial chest radiographs. Effector populations, collected by bronchoalveolar lavage (BAL) and from heparinized whole blood, were assessed for cell type, immunophenotype, and tumor cytolytic activity. Immunogenicity of human IL-2 and human serum albumin (HSA) in dogs was assessed by immunofluorescence assay. RESULTS. Two of four dogs with metastatic pulmonary osteosarcoma had complete regression of metastases; the regression remained stable for more than 12 and more than 20 months, respectively. One of two dogs with lung carcinoma had stabilization of disease for more than 8 months; the other had disease progression. Toxicity was minimal. BAL cell numbers increased more than fourfold (P = 0.01) and included significantly greater proportions and total numbers of eosinophils (P = 0.006) and lymphocytes (P = 0.008). Mean BAL effector lytic activity was significantly greater after 15 days of IL-2 liposome inhalation compared with pretreatment activity (P = 0.01); however, mean BAL lytic activity decreased after 30 days and was no longer significantly greater than pretreatment BAL lytic activity. No allergic reactions were associated with inhaled IL-2 liposome therapy. Canine antibodies against human IL-2 and HSA were detected in all dogs. CONCLUSIONS. Pet dogs with naturally occurring pulmonary metastases and primary lung carcinomas accepted inhalation treatments easily. Nontoxic and effective treatment of pulmonary metastases of osteosarcoma is possible with nebulized IL-2 liposomes.",
keywords = "dogs, inhalation, interleukin-2, liposome, lung carcinoma, pulmonary metastases",
author = "Chand Khanna and Anderson, {Peter M.} and Hasz, {Diane E.} and Emmanuel Katsanis and Mary Neville and Klausner, {Jeffrey S.}",
year = "1997",
month = "4",
day = "1",
doi = "10.1002/(SICI)1097-0142(19970401)79:7<1409::AID-CNCR19>3.0.CO;2-3",
language = "English (US)",
volume = "79",
pages = "1409--1421",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "7",

}

TY - JOUR

T1 - Interleukin-2 liposome inhalation therapy is safe and effective for dogs with spontaneous pulmonary metastases

AU - Khanna, Chand

AU - Anderson, Peter M.

AU - Hasz, Diane E.

AU - Katsanis, Emmanuel

AU - Neville, Mary

AU - Klausner, Jeffrey S.

PY - 1997/4/1

Y1 - 1997/4/1

N2 - BACKGROUND. Systemic in vivo toxicity of interleukin-2 (IL-2) has been problematic. Antineoplastic activity of IL-2 has been modest. The authors have previously demonstrated the biologic activity and safety of aerosols of IL-2 liposomes in normal dogs. They now report objective regression of naturally occurring pulmonary metastases in dogs after 1 month of nebulized IL-2 liposome therapy. METHODS. Dogs with pulmonary metastases (n = 7) and primary lung carcinoma (n = 2) were treated with aerosols of IL-2 liposomes. Response to therapy was monitored with serial chest radiographs. Effector populations, collected by bronchoalveolar lavage (BAL) and from heparinized whole blood, were assessed for cell type, immunophenotype, and tumor cytolytic activity. Immunogenicity of human IL-2 and human serum albumin (HSA) in dogs was assessed by immunofluorescence assay. RESULTS. Two of four dogs with metastatic pulmonary osteosarcoma had complete regression of metastases; the regression remained stable for more than 12 and more than 20 months, respectively. One of two dogs with lung carcinoma had stabilization of disease for more than 8 months; the other had disease progression. Toxicity was minimal. BAL cell numbers increased more than fourfold (P = 0.01) and included significantly greater proportions and total numbers of eosinophils (P = 0.006) and lymphocytes (P = 0.008). Mean BAL effector lytic activity was significantly greater after 15 days of IL-2 liposome inhalation compared with pretreatment activity (P = 0.01); however, mean BAL lytic activity decreased after 30 days and was no longer significantly greater than pretreatment BAL lytic activity. No allergic reactions were associated with inhaled IL-2 liposome therapy. Canine antibodies against human IL-2 and HSA were detected in all dogs. CONCLUSIONS. Pet dogs with naturally occurring pulmonary metastases and primary lung carcinomas accepted inhalation treatments easily. Nontoxic and effective treatment of pulmonary metastases of osteosarcoma is possible with nebulized IL-2 liposomes.

AB - BACKGROUND. Systemic in vivo toxicity of interleukin-2 (IL-2) has been problematic. Antineoplastic activity of IL-2 has been modest. The authors have previously demonstrated the biologic activity and safety of aerosols of IL-2 liposomes in normal dogs. They now report objective regression of naturally occurring pulmonary metastases in dogs after 1 month of nebulized IL-2 liposome therapy. METHODS. Dogs with pulmonary metastases (n = 7) and primary lung carcinoma (n = 2) were treated with aerosols of IL-2 liposomes. Response to therapy was monitored with serial chest radiographs. Effector populations, collected by bronchoalveolar lavage (BAL) and from heparinized whole blood, were assessed for cell type, immunophenotype, and tumor cytolytic activity. Immunogenicity of human IL-2 and human serum albumin (HSA) in dogs was assessed by immunofluorescence assay. RESULTS. Two of four dogs with metastatic pulmonary osteosarcoma had complete regression of metastases; the regression remained stable for more than 12 and more than 20 months, respectively. One of two dogs with lung carcinoma had stabilization of disease for more than 8 months; the other had disease progression. Toxicity was minimal. BAL cell numbers increased more than fourfold (P = 0.01) and included significantly greater proportions and total numbers of eosinophils (P = 0.006) and lymphocytes (P = 0.008). Mean BAL effector lytic activity was significantly greater after 15 days of IL-2 liposome inhalation compared with pretreatment activity (P = 0.01); however, mean BAL lytic activity decreased after 30 days and was no longer significantly greater than pretreatment BAL lytic activity. No allergic reactions were associated with inhaled IL-2 liposome therapy. Canine antibodies against human IL-2 and HSA were detected in all dogs. CONCLUSIONS. Pet dogs with naturally occurring pulmonary metastases and primary lung carcinomas accepted inhalation treatments easily. Nontoxic and effective treatment of pulmonary metastases of osteosarcoma is possible with nebulized IL-2 liposomes.

KW - dogs

KW - inhalation

KW - interleukin-2

KW - liposome

KW - lung carcinoma

KW - pulmonary metastases

UR - http://www.scopus.com/inward/record.url?scp=0030982904&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030982904&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1097-0142(19970401)79:7<1409::AID-CNCR19>3.0.CO;2-3

DO - 10.1002/(SICI)1097-0142(19970401)79:7<1409::AID-CNCR19>3.0.CO;2-3

M3 - Article

VL - 79

SP - 1409

EP - 1421

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 7

ER -