Cited by 2,603CAR-T cell therapy researchImmunotherapy and Immune ResponsesVirus-based gene therapy research

Cancer regression in patients after transfer of genetically engineered lymphocytes

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Morgan, Richard A., Dudley, Mark E., Wunderlich, John R., Hughes, Marybeth S., Yang, James C., Sherry, Richard M., Royal, Richard E., Topalian, Suzanne L. +8 more·2006·Science

Abstract

Through the adoptive transfer of lymphocytes after host immunodepletion, it is possible to mediate objective cancer regression in human patients with metastatic melanoma. However, the generation of tumor-specific T cells in this mode of immunotherapy is often limiting. Here we report the ability to specifically confer tumor recognition by autologous lymphocytes from peripheral blood by using a retrovirus that encodes a T cell receptor. Adoptive transfer of these transduced cells in 15 patients resulted in durable engraftment at levels exceeding 10% of peripheral blood lymphocytes for at least 2 months after the infusion. We observed high sustained levels of circulating, engineered cells at 1 year after infusion in two patients who both demonstrated objective regression of metastatic melanoma lesions. This study suggests the therapeutic potential of genetically engineered cells for the biologic therapy of cancer.

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Authors
Morgan, R. A., Dudley, M. E., Wunderlich, J. R., Hughes, M. S., Yang, J. C., Sherry, R. M., Royal, R. E., Topalian, S. L., Kammula, U. S., Restifo, N. P., Zheng, Z., Nahvi, A., de Vries, C. R., Rogers-Freezer, L. J., Mavroukakis, S. A., & Rosenberg, S. A.
Affiliations
  • National Institutes of Health (US)
  • Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
Corresponding author
Rosenberg, Steven A.
Venue
Science
Published
2006-10-06
Volume
314
Issue
5796
Pages
126-129
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2094652659
Cited by
2,603
References
19
Citations by year
2026: 58 · 2025: 58 · 2024: 71 · 2023: 88 · 2022: 99 · 2021: 113 · 2020: 125 · 2019: 122 · 2018: 117 · 2017: 129 · 2016: 123 · 2015: 147 · 2014: 111 · 2013: 182 · 2012: 175
FWCI
89.46
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (Z99 CA999999)
  • National Cancer Institute (Z01BC010763, Z01SC003811)
Topics
  • Health Sciences › Medicine › Oncology › CAR-T cell therapy research
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Keywords
T cell receptor gene transfer, retroviral transduction, adoptive immunotherapy, metastatic melanoma, tumor regression, tumor-specific T cells, cell engraftment, autologous lymphocytes
MeSH terms
Adult, Antigens, Neoplasm, Cells, Cultured, Female, Genetic Engineering, Humans, Interleukin-2, Male, Melanoma, Middle Aged, Neoplasm Proteins, Transduction, Genetic, HLA-A Antigens, Genetic Therapy, HLA-A2 Antigen, Receptors, Antigen, T-Cell, alpha-beta, Electroporation, CD8-Positive T-Lymphocytes, Transgenes, Adoptive Transfer, Cancer Vaccines, MART-1 Antigen

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