Mackensen, Andreas and Meidenbauer, Norbert and Vogl, Sandra and Laumer, Monika and Berger, Jana and Andreesen, Reinhard (2006) Phase I study of adoptive T-cell therapy using antigen-specific CD8(+) T cells for the treatment of patients with metastatic melanoma. JOURNAL OF CLINICAL ONCOLOGY, 24 (31). pp. 5060-5069. ISSN 0732-183X,
Full text not available from this repository. (Request a copy)Abstract
Purpose The adoptive transfer of in vitro generated tumor antigen-specific cytotoxic T lymphocytes (CTL) provides a promising approach to the immunotherapy of cancer. A phase I study was conducted to test the feasibility, safety, and survival of adoptively transferred Melan-A-specific CTL lines in melanoma patients. Patients and Methods Eleven HLA-A2(+) patients with metastatic melanoma received at least three intravenous infusions of Melan-A -specific CTL at 2-week intervals. CTL were generated by four rounds of in vitro stimulation of purified CD8(+) peripheral blood lymphocytes with autologous dendritic cells pulsed with an HLA-A2 binding Melan-A peptide. Each T-cell infusion was accompanied by a 6-day course of low-dose interleukin-2. Results A total of 52 T-cell infusions were administered, averaging 2.1 x 10(8) Melan-A -specific CTL per infusion. Clinical adverse effects were mild and consisted of chills and low-grade fever in seven of 11 patients. Clinical and immunologic responses revealed an antitumor response in three of 11 patients ( one complete regression, one partial regression, one mixed response), an elevated frequency of circulating Melan-A tetramer(+) T cells up to 2 weeks in all the patients with a maximal frequency of 2% of total CD8(+) T cells, an increase in eosinophils to up to 50% in seven of 11 patients, and a selective loss of Melan-A expression in lymph node metastases in two evaluated patients after T-cell transfer. Conclusion Our data indicate that the adoptive transfer of antigen-specific T cells in melanoma patients can induce clinical tumor-specific immune responses without major adverse effects.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ALLOGENEIC BONE-MARROW; TUMOR-IMMUNOTHERAPY; VIVO PERSISTENCE; LYMPHOCYTES; REGRESSION; CLONES; CANCER; DONOR; INTERLEUKIN-2; SURVIVAL; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 Jan 2021 12:15 |
| Last Modified: | 19 Jan 2021 12:15 |
| URI: | https://pred.uni-regensburg.de/id/eprint/33811 |
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