Intratumoral administration of a 1,2-dimyristyloxypropyl-3- dimethylhydroxyethyl ammonium bromide/dioleoylphosphatidylethanolamine formulation of the human interleukin-2 gene in the treatment of metastatic renal cell carcinoma

Evanthia Galanis, Patrick A. Burch, Ronald L. Richardson, Bradley Lewis, Henry C. Pitot, Stephen Frytak, Catherine S Perry, Emmanuel T. Akporiaye, Prema P. Peethambaram, Judith S. Kaur, Scott H. Okuno, Krishnan K. Unni, Joseph Rubin

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

BACKGROUND. Leuvectin (Vical Inc., San Diego, CA) is a gene transfer product in which a plasmid encoding the human interleukin-2 (IL-2) gene is complexed with the cationic lipid 1,2-dimyristyloxypropyl-3-dimethylhydroxyethyl ammonium bromide/dioleoylphosphatidylethanolamine (DMRIE/DOPE). In the current study, the authors investigated the safety and efficacy of in situ vaccination with Leuvectin in patients with metastatic renal cell carcinoma. METHODS. Thirty-one patients with metastatic renal cell carcinoma were treated with intratumorally administered Leuvectin at doses ranging from 0.75 to 4 mg. These patients subsequently were evaluated for response and for treatment-related toxicity. RESULTS. Treatment was well tolerated: no Grade 3 or 4 toxicities were observed in association with the study agent. Documented side effects included Grade 1 pain at the injection site (20%); mild (i.e., Grade 1 or 2) constitutional symptoms, including malaise/myalgia, low-grade fever, and chills (74%); Grade 1 fatigue (19%); Grade 1 or 2 nausea (10%); and Grade 2 allergy (1 occurrence). Two patients experienced partial responses, which endured for 32 months and 6 years, respectively, and 1 patient currently is experiencing a pathologic complete response, which, to date, has persisted for 50 months; thus, the overall response rate was 10%. In addition, 7 patients (23%) experienced disease stabilization for a median of 8 months (range, 4-48 months). The median duration of survival from the start of Leuvectin treatment was 11 months (range, 2-72 months), with a 1-year survival rate of 48% and a 3-year survival rate of 19%. Laboratory analysis of tumor samples revealed the presence of IL-2 plasmid DNA in six of eight patients posttreatment, increased IL-2 expression in tumor cells in four of eight patients posttreatment, and increased tumor infiltration by CD8-positive lymphocytes in five of eight patients posttreatment. CONCLUSIONS. Immunotherapy with intratumorally administered Leuvectin is safe and can lead to durable objective responses in patients with metastatic renal cell carcinoma.

Original languageEnglish (US)
Pages (from-to)2557-2566
Number of pages10
JournalCancer
Volume101
Issue number11
DOIs
StatePublished - Dec 1 2004

Fingerprint

Renal Cell Carcinoma
Interleukin-2
Genes
Therapeutics
Plasmids
Survival Rate
ammonium bromide
dioleoyl phosphatidylethanolamine
CD8-Positive T-Lymphocytes
Neoplasms
Chills
Myalgia
Immunotherapy
Nausea
Fatigue
Hypersensitivity
Vaccination
Fever
Leuvectin
Lipids

Keywords

  • Gene therapy
  • Immunotherapy
  • Interleukin-2
  • Leuvectin
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Intratumoral administration of a 1,2-dimyristyloxypropyl-3- dimethylhydroxyethyl ammonium bromide/dioleoylphosphatidylethanolamine formulation of the human interleukin-2 gene in the treatment of metastatic renal cell carcinoma. / Galanis, Evanthia; Burch, Patrick A.; Richardson, Ronald L.; Lewis, Bradley; Pitot, Henry C.; Frytak, Stephen; Perry, Catherine S; Akporiaye, Emmanuel T.; Peethambaram, Prema P.; Kaur, Judith S.; Okuno, Scott H.; Unni, Krishnan K.; Rubin, Joseph.

In: Cancer, Vol. 101, No. 11, 01.12.2004, p. 2557-2566.

Research output: Contribution to journalArticle

Galanis, E, Burch, PA, Richardson, RL, Lewis, B, Pitot, HC, Frytak, S, Perry, CS, Akporiaye, ET, Peethambaram, PP, Kaur, JS, Okuno, SH, Unni, KK & Rubin, J 2004, 'Intratumoral administration of a 1,2-dimyristyloxypropyl-3- dimethylhydroxyethyl ammonium bromide/dioleoylphosphatidylethanolamine formulation of the human interleukin-2 gene in the treatment of metastatic renal cell carcinoma', Cancer, vol. 101, no. 11, pp. 2557-2566. https://doi.org/10.1002/cncr.20653
Galanis, Evanthia ; Burch, Patrick A. ; Richardson, Ronald L. ; Lewis, Bradley ; Pitot, Henry C. ; Frytak, Stephen ; Perry, Catherine S ; Akporiaye, Emmanuel T. ; Peethambaram, Prema P. ; Kaur, Judith S. ; Okuno, Scott H. ; Unni, Krishnan K. ; Rubin, Joseph. / Intratumoral administration of a 1,2-dimyristyloxypropyl-3- dimethylhydroxyethyl ammonium bromide/dioleoylphosphatidylethanolamine formulation of the human interleukin-2 gene in the treatment of metastatic renal cell carcinoma. In: Cancer. 2004 ; Vol. 101, No. 11. pp. 2557-2566.
@article{9655d837dcf24f16bf6795f899e71e49,
title = "Intratumoral administration of a 1,2-dimyristyloxypropyl-3- dimethylhydroxyethyl ammonium bromide/dioleoylphosphatidylethanolamine formulation of the human interleukin-2 gene in the treatment of metastatic renal cell carcinoma",
abstract = "BACKGROUND. Leuvectin (Vical Inc., San Diego, CA) is a gene transfer product in which a plasmid encoding the human interleukin-2 (IL-2) gene is complexed with the cationic lipid 1,2-dimyristyloxypropyl-3-dimethylhydroxyethyl ammonium bromide/dioleoylphosphatidylethanolamine (DMRIE/DOPE). In the current study, the authors investigated the safety and efficacy of in situ vaccination with Leuvectin in patients with metastatic renal cell carcinoma. METHODS. Thirty-one patients with metastatic renal cell carcinoma were treated with intratumorally administered Leuvectin at doses ranging from 0.75 to 4 mg. These patients subsequently were evaluated for response and for treatment-related toxicity. RESULTS. Treatment was well tolerated: no Grade 3 or 4 toxicities were observed in association with the study agent. Documented side effects included Grade 1 pain at the injection site (20{\%}); mild (i.e., Grade 1 or 2) constitutional symptoms, including malaise/myalgia, low-grade fever, and chills (74{\%}); Grade 1 fatigue (19{\%}); Grade 1 or 2 nausea (10{\%}); and Grade 2 allergy (1 occurrence). Two patients experienced partial responses, which endured for 32 months and 6 years, respectively, and 1 patient currently is experiencing a pathologic complete response, which, to date, has persisted for 50 months; thus, the overall response rate was 10{\%}. In addition, 7 patients (23{\%}) experienced disease stabilization for a median of 8 months (range, 4-48 months). The median duration of survival from the start of Leuvectin treatment was 11 months (range, 2-72 months), with a 1-year survival rate of 48{\%} and a 3-year survival rate of 19{\%}. Laboratory analysis of tumor samples revealed the presence of IL-2 plasmid DNA in six of eight patients posttreatment, increased IL-2 expression in tumor cells in four of eight patients posttreatment, and increased tumor infiltration by CD8-positive lymphocytes in five of eight patients posttreatment. CONCLUSIONS. Immunotherapy with intratumorally administered Leuvectin is safe and can lead to durable objective responses in patients with metastatic renal cell carcinoma.",
keywords = "Gene therapy, Immunotherapy, Interleukin-2, Leuvectin, Renal cell carcinoma",
author = "Evanthia Galanis and Burch, {Patrick A.} and Richardson, {Ronald L.} and Bradley Lewis and Pitot, {Henry C.} and Stephen Frytak and Perry, {Catherine S} and Akporiaye, {Emmanuel T.} and Peethambaram, {Prema P.} and Kaur, {Judith S.} and Okuno, {Scott H.} and Unni, {Krishnan K.} and Joseph Rubin",
year = "2004",
month = "12",
day = "1",
doi = "10.1002/cncr.20653",
language = "English (US)",
volume = "101",
pages = "2557--2566",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "11",

}

TY - JOUR

T1 - Intratumoral administration of a 1,2-dimyristyloxypropyl-3- dimethylhydroxyethyl ammonium bromide/dioleoylphosphatidylethanolamine formulation of the human interleukin-2 gene in the treatment of metastatic renal cell carcinoma

AU - Galanis, Evanthia

AU - Burch, Patrick A.

AU - Richardson, Ronald L.

AU - Lewis, Bradley

AU - Pitot, Henry C.

AU - Frytak, Stephen

AU - Perry, Catherine S

AU - Akporiaye, Emmanuel T.

AU - Peethambaram, Prema P.

AU - Kaur, Judith S.

AU - Okuno, Scott H.

AU - Unni, Krishnan K.

AU - Rubin, Joseph

PY - 2004/12/1

Y1 - 2004/12/1

N2 - BACKGROUND. Leuvectin (Vical Inc., San Diego, CA) is a gene transfer product in which a plasmid encoding the human interleukin-2 (IL-2) gene is complexed with the cationic lipid 1,2-dimyristyloxypropyl-3-dimethylhydroxyethyl ammonium bromide/dioleoylphosphatidylethanolamine (DMRIE/DOPE). In the current study, the authors investigated the safety and efficacy of in situ vaccination with Leuvectin in patients with metastatic renal cell carcinoma. METHODS. Thirty-one patients with metastatic renal cell carcinoma were treated with intratumorally administered Leuvectin at doses ranging from 0.75 to 4 mg. These patients subsequently were evaluated for response and for treatment-related toxicity. RESULTS. Treatment was well tolerated: no Grade 3 or 4 toxicities were observed in association with the study agent. Documented side effects included Grade 1 pain at the injection site (20%); mild (i.e., Grade 1 or 2) constitutional symptoms, including malaise/myalgia, low-grade fever, and chills (74%); Grade 1 fatigue (19%); Grade 1 or 2 nausea (10%); and Grade 2 allergy (1 occurrence). Two patients experienced partial responses, which endured for 32 months and 6 years, respectively, and 1 patient currently is experiencing a pathologic complete response, which, to date, has persisted for 50 months; thus, the overall response rate was 10%. In addition, 7 patients (23%) experienced disease stabilization for a median of 8 months (range, 4-48 months). The median duration of survival from the start of Leuvectin treatment was 11 months (range, 2-72 months), with a 1-year survival rate of 48% and a 3-year survival rate of 19%. Laboratory analysis of tumor samples revealed the presence of IL-2 plasmid DNA in six of eight patients posttreatment, increased IL-2 expression in tumor cells in four of eight patients posttreatment, and increased tumor infiltration by CD8-positive lymphocytes in five of eight patients posttreatment. CONCLUSIONS. Immunotherapy with intratumorally administered Leuvectin is safe and can lead to durable objective responses in patients with metastatic renal cell carcinoma.

AB - BACKGROUND. Leuvectin (Vical Inc., San Diego, CA) is a gene transfer product in which a plasmid encoding the human interleukin-2 (IL-2) gene is complexed with the cationic lipid 1,2-dimyristyloxypropyl-3-dimethylhydroxyethyl ammonium bromide/dioleoylphosphatidylethanolamine (DMRIE/DOPE). In the current study, the authors investigated the safety and efficacy of in situ vaccination with Leuvectin in patients with metastatic renal cell carcinoma. METHODS. Thirty-one patients with metastatic renal cell carcinoma were treated with intratumorally administered Leuvectin at doses ranging from 0.75 to 4 mg. These patients subsequently were evaluated for response and for treatment-related toxicity. RESULTS. Treatment was well tolerated: no Grade 3 or 4 toxicities were observed in association with the study agent. Documented side effects included Grade 1 pain at the injection site (20%); mild (i.e., Grade 1 or 2) constitutional symptoms, including malaise/myalgia, low-grade fever, and chills (74%); Grade 1 fatigue (19%); Grade 1 or 2 nausea (10%); and Grade 2 allergy (1 occurrence). Two patients experienced partial responses, which endured for 32 months and 6 years, respectively, and 1 patient currently is experiencing a pathologic complete response, which, to date, has persisted for 50 months; thus, the overall response rate was 10%. In addition, 7 patients (23%) experienced disease stabilization for a median of 8 months (range, 4-48 months). The median duration of survival from the start of Leuvectin treatment was 11 months (range, 2-72 months), with a 1-year survival rate of 48% and a 3-year survival rate of 19%. Laboratory analysis of tumor samples revealed the presence of IL-2 plasmid DNA in six of eight patients posttreatment, increased IL-2 expression in tumor cells in four of eight patients posttreatment, and increased tumor infiltration by CD8-positive lymphocytes in five of eight patients posttreatment. CONCLUSIONS. Immunotherapy with intratumorally administered Leuvectin is safe and can lead to durable objective responses in patients with metastatic renal cell carcinoma.

KW - Gene therapy

KW - Immunotherapy

KW - Interleukin-2

KW - Leuvectin

KW - Renal cell carcinoma

UR - http://www.scopus.com/inward/record.url?scp=8844237512&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=8844237512&partnerID=8YFLogxK

U2 - 10.1002/cncr.20653

DO - 10.1002/cncr.20653

M3 - Article

VL - 101

SP - 2557

EP - 2566

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 11

ER -