GENE THERAPY FOR CANCER

  • Rosenblatt, Joseph D (PI)
  • Belldegrun, Arie (PI)
  • McBride, William H. (PI)
  • Shau, Hungyi (PI)
  • Economou, James S. (PI)

Project: Research project

Description

This Program explores the use of somatic gene therapy to augment the host
immune response to cancer. The various projects will genetically modify
effector cells to improve their anti-tumor activity or modify tumor cells
to improve immunogenicity. Basic and preclinical investigations will explore methods of optimal gene
transfer into T lymphocytes, macrophages and tumor cells using retroviral
and adeno-associated virus vectors. Mechanistic studies will focus on ways
to improve anti-tumor activity of tumor-infiltrating lymphocytes (TIL) and
macrophages using cytokine genes such as IL-7 and IL-6 and cytotoxin genes
such as perforin and defensin. Efforts to improve tumor immunogenicity
will employ cytokine gene transduction or modulation of MHC expression by
altering oncogene expression. The goal will be to develop genetically-
engineered vaccines capable of stimulating tumor immunity or generating
immune lymphocytes in draining lymph nodes suitable for adoptive
immunotherapy trials. Preclinical animal models, including the use of
SCID/hu mice, will study interactions between genetically modified human
effector and tumor cells in vivo. Clinical trials are proposed for the gene therapy of melanoma, renal
cancer, leukemia and neuroblastoma that directly translate basic and
preclinical efforts. In summary, we plan a comprehensive basic, preclinical, and clinical
program of highly interactive cancer gene therapy projects.
StatusFinished
Effective start/end date9/30/9212/31/98

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Cell Engineering
Genetic Engineering
Neuroblastoma
Aptitude
Residual Neoplasm
Cytokines
Granulocyte-Macrophage Colony-Stimulating Factor
Interferon-gamma
Genes
T-Lymphocytes
Active Immunotherapy
Neoplasms
Clinical Trials, Phase I
HLA-A Antigens
HLA-B Antigens
Autologous Transplantation
Cell Line
Bone Marrow Transplantation
Human T-lymphotropic virus 1
Recurrence

ASJC

  • Medicine(all)