Immunotherapy for cancer by direct gene transfer into tumors

Gary J. Nabel, Alfred E. Chang, Elizabeth G. Nabel, Gregory E. Plautz, William Ensminger, Bernard A. Fox, Phillip Felgner, Suyu Shu, Kyung Cho

Research output: Contribution to journalArticle

Abstract

The goal of immunotherapy is to stimulate the immune system by modification of tumor cells or expansion of lymphocytes which respond specifically to tumor antigens. In this study, we will apply techniques of direct gene transfer to enhance the immune response against tumors in vivo. Patients with advanced cancer who have failed all effective therapy will be treated by injection of a DNA/liposome complex directly within the tumor. DNA will be used which encodes a heterodimeric cell surface protein recognized in the transplantation response. These genes include the HLA-B7 histocompatibility antigen and β-2 microglobulin gene in a non-viral eukaryotic expression vector plasmid. For this vector, a safe and effective dose to introduce this recombinant gene in HLA-B7- patients will be established. HLA-B7 expression will be confirmed in vivo, and the immune response stimulated by the expression of this antigen will be characterized. We will also determine whether this treatment facilitates tumor regression alone or in combination with other treatment modalities. This study will employ a similar strategy to our previous gene therapy protocol, but employs four improvements in technology, including more efficacious liposomes, optimized vector expression, catheter delivery and application to other several types of cancer. These studies will facilitate the development of other approaches, using different recombinant genes or in combination with cytokines or adoptive T cell therapy, to augment tumor immunity, and allow for greater potential efficacy. This method will also establish the safety of this non-viral approach to gene therapy, which could potentially be extended to treat a variety of other human diseases.

Original languageEnglish (US)
Pages (from-to)57-77
Number of pages21
JournalHuman Gene Therapy
Volume5
Issue number1
StatePublished - Jan 1994
Externally publishedYes

Fingerprint

Neoplasm Genes
Immunotherapy
HLA-B7 Antigen
Neoplasms
Liposomes
Genetic Therapy
Genes
Gene Transfer Techniques
Histocompatibility Antigens
DNA
Neoplasm Antigens
Cell- and Tissue-Based Therapy
Immune System
Immunity
Membrane Proteins
Plasmids
Therapeutics
Catheters
Transplantation
Lymphocytes

ASJC Scopus subject areas

  • Genetics

Cite this

Nabel, G. J., Chang, A. E., Nabel, E. G., Plautz, G. E., Ensminger, W., Fox, B. A., ... Cho, K. (1994). Immunotherapy for cancer by direct gene transfer into tumors. Human Gene Therapy, 5(1), 57-77.

Immunotherapy for cancer by direct gene transfer into tumors. / Nabel, Gary J.; Chang, Alfred E.; Nabel, Elizabeth G.; Plautz, Gregory E.; Ensminger, William; Fox, Bernard A.; Felgner, Phillip; Shu, Suyu; Cho, Kyung.

In: Human Gene Therapy, Vol. 5, No. 1, 01.1994, p. 57-77.

Research output: Contribution to journalArticle

Nabel, GJ, Chang, AE, Nabel, EG, Plautz, GE, Ensminger, W, Fox, BA, Felgner, P, Shu, S & Cho, K 1994, 'Immunotherapy for cancer by direct gene transfer into tumors', Human Gene Therapy, vol. 5, no. 1, pp. 57-77.
Nabel GJ, Chang AE, Nabel EG, Plautz GE, Ensminger W, Fox BA et al. Immunotherapy for cancer by direct gene transfer into tumors. Human Gene Therapy. 1994 Jan;5(1):57-77.
Nabel, Gary J. ; Chang, Alfred E. ; Nabel, Elizabeth G. ; Plautz, Gregory E. ; Ensminger, William ; Fox, Bernard A. ; Felgner, Phillip ; Shu, Suyu ; Cho, Kyung. / Immunotherapy for cancer by direct gene transfer into tumors. In: Human Gene Therapy. 1994 ; Vol. 5, No. 1. pp. 57-77.
@article{821914ed15e14bf0add4e7241cb2a7b9,
title = "Immunotherapy for cancer by direct gene transfer into tumors",
abstract = "The goal of immunotherapy is to stimulate the immune system by modification of tumor cells or expansion of lymphocytes which respond specifically to tumor antigens. In this study, we will apply techniques of direct gene transfer to enhance the immune response against tumors in vivo. Patients with advanced cancer who have failed all effective therapy will be treated by injection of a DNA/liposome complex directly within the tumor. DNA will be used which encodes a heterodimeric cell surface protein recognized in the transplantation response. These genes include the HLA-B7 histocompatibility antigen and β-2 microglobulin gene in a non-viral eukaryotic expression vector plasmid. For this vector, a safe and effective dose to introduce this recombinant gene in HLA-B7- patients will be established. HLA-B7 expression will be confirmed in vivo, and the immune response stimulated by the expression of this antigen will be characterized. We will also determine whether this treatment facilitates tumor regression alone or in combination with other treatment modalities. This study will employ a similar strategy to our previous gene therapy protocol, but employs four improvements in technology, including more efficacious liposomes, optimized vector expression, catheter delivery and application to other several types of cancer. These studies will facilitate the development of other approaches, using different recombinant genes or in combination with cytokines or adoptive T cell therapy, to augment tumor immunity, and allow for greater potential efficacy. This method will also establish the safety of this non-viral approach to gene therapy, which could potentially be extended to treat a variety of other human diseases.",
author = "Nabel, {Gary J.} and Chang, {Alfred E.} and Nabel, {Elizabeth G.} and Plautz, {Gregory E.} and William Ensminger and Fox, {Bernard A.} and Phillip Felgner and Suyu Shu and Kyung Cho",
year = "1994",
month = "1",
language = "English (US)",
volume = "5",
pages = "57--77",
journal = "Human Gene Therapy",
issn = "1043-0342",
publisher = "Mary Ann Liebert Inc.",
number = "1",

}

TY - JOUR

T1 - Immunotherapy for cancer by direct gene transfer into tumors

AU - Nabel, Gary J.

AU - Chang, Alfred E.

AU - Nabel, Elizabeth G.

AU - Plautz, Gregory E.

AU - Ensminger, William

AU - Fox, Bernard A.

AU - Felgner, Phillip

AU - Shu, Suyu

AU - Cho, Kyung

PY - 1994/1

Y1 - 1994/1

N2 - The goal of immunotherapy is to stimulate the immune system by modification of tumor cells or expansion of lymphocytes which respond specifically to tumor antigens. In this study, we will apply techniques of direct gene transfer to enhance the immune response against tumors in vivo. Patients with advanced cancer who have failed all effective therapy will be treated by injection of a DNA/liposome complex directly within the tumor. DNA will be used which encodes a heterodimeric cell surface protein recognized in the transplantation response. These genes include the HLA-B7 histocompatibility antigen and β-2 microglobulin gene in a non-viral eukaryotic expression vector plasmid. For this vector, a safe and effective dose to introduce this recombinant gene in HLA-B7- patients will be established. HLA-B7 expression will be confirmed in vivo, and the immune response stimulated by the expression of this antigen will be characterized. We will also determine whether this treatment facilitates tumor regression alone or in combination with other treatment modalities. This study will employ a similar strategy to our previous gene therapy protocol, but employs four improvements in technology, including more efficacious liposomes, optimized vector expression, catheter delivery and application to other several types of cancer. These studies will facilitate the development of other approaches, using different recombinant genes or in combination with cytokines or adoptive T cell therapy, to augment tumor immunity, and allow for greater potential efficacy. This method will also establish the safety of this non-viral approach to gene therapy, which could potentially be extended to treat a variety of other human diseases.

AB - The goal of immunotherapy is to stimulate the immune system by modification of tumor cells or expansion of lymphocytes which respond specifically to tumor antigens. In this study, we will apply techniques of direct gene transfer to enhance the immune response against tumors in vivo. Patients with advanced cancer who have failed all effective therapy will be treated by injection of a DNA/liposome complex directly within the tumor. DNA will be used which encodes a heterodimeric cell surface protein recognized in the transplantation response. These genes include the HLA-B7 histocompatibility antigen and β-2 microglobulin gene in a non-viral eukaryotic expression vector plasmid. For this vector, a safe and effective dose to introduce this recombinant gene in HLA-B7- patients will be established. HLA-B7 expression will be confirmed in vivo, and the immune response stimulated by the expression of this antigen will be characterized. We will also determine whether this treatment facilitates tumor regression alone or in combination with other treatment modalities. This study will employ a similar strategy to our previous gene therapy protocol, but employs four improvements in technology, including more efficacious liposomes, optimized vector expression, catheter delivery and application to other several types of cancer. These studies will facilitate the development of other approaches, using different recombinant genes or in combination with cytokines or adoptive T cell therapy, to augment tumor immunity, and allow for greater potential efficacy. This method will also establish the safety of this non-viral approach to gene therapy, which could potentially be extended to treat a variety of other human diseases.

UR - http://www.scopus.com/inward/record.url?scp=0028170350&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028170350&partnerID=8YFLogxK

M3 - Article

C2 - 8155772

AN - SCOPUS:0028170350

VL - 5

SP - 57

EP - 77

JO - Human Gene Therapy

JF - Human Gene Therapy

SN - 1043-0342

IS - 1

ER -