Cancer regression in patients after transfer of genetically engineered lymphocytes
Open accessAbstract
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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Identifying specific tumor-reactive lymphocytes for TIL therapy, especially in patients with tumors other than melanoma, can be challenging.
“However, identifying these specific lymphocytes, especially in patients with tumors other than melanoma, can be challenging [141].”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [141]
Successful TIL therapy relies on the presence of preexisting tumor-reactive lymphocytes in patients, which can be expanded ex vivo.
“Successful TIL therapy relies on the presence of preexisting tumor-reactive lymphocytes in patients, which can be expanded ex vivo.”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [141]
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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.
- ORCID
- Venue
- Science
- Published
- 2006-10-06
- Volume
- 314
- Issue
- 5796
- Pages
- 126-129
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2267026
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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