Adoptive Cellular Therapy With Tumor Vaccine Draining Lymph Node Lymphocytes After Vaccination With HLA-B7/&bgr;2-Microglobulin Gene-Modified Autologous Tumor Cells
作者:
Sybren Meijer,
Annemieke Dols,
Walter Urba,
Hong-Ming Hu,
John Smith,
John Vetto,
William Wood,
Teri Doran,
Yiwei Chu,
Philip Sayaharuban,
W. Alvord,
Bernard Fox,
期刊:
Journal of Immunotherapy
(OVID Available online 2002)
卷期:
Volume 25,
issue 4
页码: 359-372
ISSN:1524-9557
年代: 2002
出版商: OVID
关键词: Adoptive immunotherapy;Tumor vaccine;Melanoma;Renal cell cancer
数据来源: OVID
摘要:
Adoptive immunotherapy with anti-CD3-expanded lymphocytes from lymph nodes draining alloantigen gene-modified autologous tumor vaccines is an effective treatment of poorly immunogenic murine tumors. This phase I/II study was performed to determine the feasibility and toxicity of combining ex vivo gene transfer of autologous tumor cells and adoptive immunotherapy with anti-CD3-expanded tumor vaccine draining lymph node lymphocytes (TVDLN) in patients with metastatic melanoma and renal cell cancer (RCC). To facilitate the generation of tumor-specific lymphocytes in the TVDLN, autologous tumor cells were modified by gene transfer ex vivo to express the alloantigen HLA-B7, a modification that has the potential to enhance the immunogenicity of the tumor cells. After vaccination with gene-modified tumor cells, patients' lymph nodes were harvested; TVDLN lymphocytes were activated and expanded ex vivo with anti-CD3 and interleukin-2 (IL-2), and adoptively transferred to patients in combination with systemic IL-2. Twenty patients, nine with melanoma and 11 with RCC were treated. Tumor was harvested successfully in all 20 patients. Ex vivo gene transfer was performed using lipofection with a lipid: DNA plasmid complex containing the genes for HLA-B7 and &bgr;2-microglobulin. The mean expression of HLA-B7 by autologous tumor cells after gene transfer was 4.53% (range 0.3%–12.1%). Lymph nodes were harvested from all 20 patients with a mean of 53 × 107and 60 × 107cells obtained from the gene-modified and unmodified tumor vaccine sites, respectively. Successful expansion of adequate TVDLN was accomplished in 19 of 20 harvests of unmodified vaccines and in 18 of 20 gene-modified vaccines. No major toxicities were noted after vaccination with autologous tumor cells or adoptive transfer of ex vivo activated TVDLN lymphocytes. Typical IL-2-related toxicities were observed in all patients. No objective tumor regressions were observed. MHC class I restricted, tumor-specific cytokine secretion was observed in lymphocytes from TVDLN and the peripheral blood of vaccinated patients.
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