Advances in the biological therapy and gene therapy of malignant disease

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Biological and gene therapy of cancer have become important components of clinical cancer research. Advances in this area are based on evidence for the presence of tumor antigens, antitumor immune responses, evasion of host control by tumors, and the recognition of host defense failure in cancer patients. These mechanisms are being corrected or exploited in the development of biological and gene therapy. Over the last decade, 9 biological therapies have received Food and Drug Administration approval, and another 12 appear promising and will likely be approved in the next few years. Our approach to gene therapy has been to allogenize tumors by the direct intratumoral injection of HLA-B7/β2-microglobulin genes as plasmid DNA in a cationic lipid into patients with malignant melanoma. In four Phase I studies, we found a 36% response by the local injected tumor and a 19% systemic antitumor response. In other cancers, gene transfer, expression, and an intratumoral T-cell response were seen, but no clinical response was seen. A variety of follow-up studies with HLA-B7 and other genes are planned. Evasion of host control is now a major target of gene therapy. Strategies to overcome this include up-regulation of MHC and introduction of cell adhesion molecules into tumor cells, suppression of transforming growth factor β and interleukin 10 production by tumor cells, and blockade of the fas ligand-fas interaction between tumor cells and attacking lymphocytes. With these approaches, it seems likely that gene therapy may become the fifth major modality of cancer treatment in the next decade.

Original languageEnglish (US)
Pages (from-to)2623-2629
Number of pages7
JournalClinical Cancer Research
Volume3
Issue number12 II
StatePublished - Dec 1997

Fingerprint

Biological Therapy
Genetic Therapy
Neoplasms
HLA-B7 Antigen
Immune Evasion
Drug Approval
Fas Ligand Protein
Neoplasm Genes
Cell Adhesion Molecules
Transforming Growth Factors
Neoplasm Antigens
United States Food and Drug Administration
Interleukin-10
Genes
Melanoma
Plasmids
Up-Regulation
Lymphocytes
T-Lymphocytes
Lipids

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Advances in the biological therapy and gene therapy of malignant disease. / Hersh, Evan M; Stopeck, Alison T.

In: Clinical Cancer Research, Vol. 3, No. 12 II, 12.1997, p. 2623-2629.

Research output: Contribution to journalArticle

@article{348649f472ce43f7b50bd3b48490946f,
title = "Advances in the biological therapy and gene therapy of malignant disease",
abstract = "Biological and gene therapy of cancer have become important components of clinical cancer research. Advances in this area are based on evidence for the presence of tumor antigens, antitumor immune responses, evasion of host control by tumors, and the recognition of host defense failure in cancer patients. These mechanisms are being corrected or exploited in the development of biological and gene therapy. Over the last decade, 9 biological therapies have received Food and Drug Administration approval, and another 12 appear promising and will likely be approved in the next few years. Our approach to gene therapy has been to allogenize tumors by the direct intratumoral injection of HLA-B7/β2-microglobulin genes as plasmid DNA in a cationic lipid into patients with malignant melanoma. In four Phase I studies, we found a 36{\%} response by the local injected tumor and a 19{\%} systemic antitumor response. In other cancers, gene transfer, expression, and an intratumoral T-cell response were seen, but no clinical response was seen. A variety of follow-up studies with HLA-B7 and other genes are planned. Evasion of host control is now a major target of gene therapy. Strategies to overcome this include up-regulation of MHC and introduction of cell adhesion molecules into tumor cells, suppression of transforming growth factor β and interleukin 10 production by tumor cells, and blockade of the fas ligand-fas interaction between tumor cells and attacking lymphocytes. With these approaches, it seems likely that gene therapy may become the fifth major modality of cancer treatment in the next decade.",
author = "Hersh, {Evan M} and Stopeck, {Alison T}",
year = "1997",
month = "12",
language = "English (US)",
volume = "3",
pages = "2623--2629",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "12 II",

}

TY - JOUR

T1 - Advances in the biological therapy and gene therapy of malignant disease

AU - Hersh, Evan M

AU - Stopeck, Alison T

PY - 1997/12

Y1 - 1997/12

N2 - Biological and gene therapy of cancer have become important components of clinical cancer research. Advances in this area are based on evidence for the presence of tumor antigens, antitumor immune responses, evasion of host control by tumors, and the recognition of host defense failure in cancer patients. These mechanisms are being corrected or exploited in the development of biological and gene therapy. Over the last decade, 9 biological therapies have received Food and Drug Administration approval, and another 12 appear promising and will likely be approved in the next few years. Our approach to gene therapy has been to allogenize tumors by the direct intratumoral injection of HLA-B7/β2-microglobulin genes as plasmid DNA in a cationic lipid into patients with malignant melanoma. In four Phase I studies, we found a 36% response by the local injected tumor and a 19% systemic antitumor response. In other cancers, gene transfer, expression, and an intratumoral T-cell response were seen, but no clinical response was seen. A variety of follow-up studies with HLA-B7 and other genes are planned. Evasion of host control is now a major target of gene therapy. Strategies to overcome this include up-regulation of MHC and introduction of cell adhesion molecules into tumor cells, suppression of transforming growth factor β and interleukin 10 production by tumor cells, and blockade of the fas ligand-fas interaction between tumor cells and attacking lymphocytes. With these approaches, it seems likely that gene therapy may become the fifth major modality of cancer treatment in the next decade.

AB - Biological and gene therapy of cancer have become important components of clinical cancer research. Advances in this area are based on evidence for the presence of tumor antigens, antitumor immune responses, evasion of host control by tumors, and the recognition of host defense failure in cancer patients. These mechanisms are being corrected or exploited in the development of biological and gene therapy. Over the last decade, 9 biological therapies have received Food and Drug Administration approval, and another 12 appear promising and will likely be approved in the next few years. Our approach to gene therapy has been to allogenize tumors by the direct intratumoral injection of HLA-B7/β2-microglobulin genes as plasmid DNA in a cationic lipid into patients with malignant melanoma. In four Phase I studies, we found a 36% response by the local injected tumor and a 19% systemic antitumor response. In other cancers, gene transfer, expression, and an intratumoral T-cell response were seen, but no clinical response was seen. A variety of follow-up studies with HLA-B7 and other genes are planned. Evasion of host control is now a major target of gene therapy. Strategies to overcome this include up-regulation of MHC and introduction of cell adhesion molecules into tumor cells, suppression of transforming growth factor β and interleukin 10 production by tumor cells, and blockade of the fas ligand-fas interaction between tumor cells and attacking lymphocytes. With these approaches, it seems likely that gene therapy may become the fifth major modality of cancer treatment in the next decade.

UR - http://www.scopus.com/inward/record.url?scp=0031426985&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031426985&partnerID=8YFLogxK

M3 - Article

C2 - 10068264

AN - SCOPUS:0031426985

VL - 3

SP - 2623

EP - 2629

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 12 II

ER -