Cancer Regression and Autoimmunity in Patients After Clonal Repopulation with Antitumor Lymphocytes
Abstract
We report here the adoptive transfer, to patients with metastatic melanoma, of highly selected tumor-reactive T cells directed against overexpressed self-derived differentiation antigens after a nonmyeloablative conditioning regimen. This approach resulted in the persistent clonal repopulation of T cells in those cancer patients, with the transferred cells proliferating in vivo, displaying functional activity, and trafficking to tumor sites. This led to regression of the patients' metastatic melanoma as well as to the onset of autoimmune melanocyte destruction. This approach presents new possibilities for the treatment of patients with cancer as well as patients with human immunodeficiency virus–related acquired immunodeficiency syndrome and other infectious diseases.
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Adoptive cell therapy involves genetically modifying T cells to express a chimeric antigen receptor or T cell receptor that recognizes specific antigens displayed on tumors, leading to clinical benefits.
“Adoptive cell therapy is an immunotherapy that involves genetically modifying T cells to express either a chimeric antigen receptor or T cell receptor (TCR) that can recognize specific antigens displayed on tumors, leading to clinical benefits.602,603”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [603]
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- Authors
- Dudley, M. E., Wunderlich, J. R., Robbins, P. F., Yang, J. C., Hwu, P., Schwartzentruber, D. J., Topalian, S. L., Sherry, R., Restifo, N. P., Hubicki, A. M., Robinson, M. R., Raffeld, M., Duray, P., Seipp, C. A., Rogers-Freezer, L., Morton, K. E., Mavroukakis, S. A., White, D. E., & Rosenberg, S. A.
- Affiliations
- National Cancer Institute (MY)
- National Eye Institute (US)
- National Institutes of Health (US)
- Corresponding author
- Rosenberg, Steven A.
- ORCID
- Venue
- Science
- Published
- 2002-10-25
- Volume
- 298
- Issue
- 5594
- Pages
- 850-854
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2151246207
- Cited by
- 2,823
- References
- 28
- Citations by year
- 2026: 37 · 2025: 54 · 2024: 55 · 2023: 103 · 2022: 77 · 2021: 91 · 2020: 101 · 2019: 76 · 2018: 92 · 2017: 92 · 2016: 100 · 2015: 118 · 2014: 97 · 2013: 124 · 2012: 116
- FWCI
- 53.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (Z99 CA999999)
- National Cancer Institute (Z01BC010763)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Keywords
- adoptive T cell therapy, metastatic melanoma, tumor regression, autoimmunity, differentiation antigens, nonmyeloablative conditioning, melanocyte destruction, autoreactive T cells
- MeSH terms
- Adolescent, Adult, Histocompatibility Antigens Class II, Antigens, Neoplasm, Clone Cells, Female, Humans, Interleukin-2, Lymphocyte Depletion, Male, Melanocytes, Melanoma, Middle Aged, Neoplasm Proteins, T-Lymphocytes, Histocompatibility Antigens Class I, Autoimmunity, HLA-A2 Antigen, Cytokines, Immunotherapy, Adoptive, Lymphocytes, Tumor-Infiltrating, Receptors, Antigen, T-Cell, alpha-beta, Treatment Outcome, CD8-Positive T-Lymphocytes, Lymphocyte Count, MART-1 Antigen
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