Cancer Regression in Patients with Metastatic Melanoma after the Transfer of Autologous Antitumor Lymphocytes

Our recent clinical trials demonstrate that autologous cell transfer after lymphodepleting chemotherapy can cause the regression of large, vascularized tumors in patients with refractory metastatic melanoma. Eighteen of 35 patients treated with tumor-reactive lymphocyte cultures experienced an objec...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2004-10, Vol.101 (Suppl 2), p.14639-14645
Main Authors: Rosenberg, Steven A., Dudley, Mark E.
Format: Article
Language:English
Subjects:
Adult
Antigens
Antigens, Neoplasm
Cancer
Cells
Cells, Cultured
Chemotherapy
Clinical trials
Colloquium Papers
Cultured tumor cells
Female
Humans
Immunotherapy, Adoptive - methods
Immunotherapy, Adoptive - trends
In Vitro Techniques
Lymphocyte Transfusion
Lymphocytes
Lymphocytes, Tumor-Infiltrating - immunology
Male
Melanoma
Melanoma - immunology
Melanoma - secondary
Melanoma - therapy
Middle Aged
Patients
Reactivity
T lymphocytes
Transplantation, Autologous
Tumor cell line
Tumors
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Summary:Our recent clinical trials demonstrate that autologous cell transfer after lymphodepleting chemotherapy can cause the regression of large, vascularized tumors in patients with refractory metastatic melanoma. Eighteen of 35 patients treated with tumor-reactive lymphocyte cultures experienced an objective clinical response (>50% reduction in tumor), including four complete responders. In some patients, tumor regression was accompanied by a large in vivo expansion of the administered antitumor lymphocytes, which persisted in peripheral blood at >70% of total lymphocytes for many months after transfer. The cells capable of mediating tumor regression consisted of heterogeneous lymphocyte populations with high avidity for tumor antigens that were derived from tumor-infiltrating lymphocytes cultured for limited times in vitro. The success of this treatment likely results from the ability to infuse large numbers of activated antitumor lymphocytes into an appropriate host homeostatic environment depleted of regulatory T cells. These studies are elucidating the requirements for successful immunotherapy of patients with advanced metastatic disease and are leading to additional clinical trials with gene-modified lymphocytes.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0405730101