期刊
CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 58, 期 2, 页码 209-220出版社
SPRINGER
DOI: 10.1007/s00262-008-0542-1
关键词
Human; SCID; Antigen-specific CD8+T cells; aAPC; Melanoma; Adoptive immunotherapy
资金
- NCI NIH HHS [R01 CA108835, CA108835, R01 CA108835-01] Funding Source: Medline
- NIAID NIH HHS [R01 AI029575-16, AI 44129, R01 AI029575, R01 AI044129, R01 AI044129-01A1, AI 29575] Funding Source: Medline
Adoptive immunotherapy for treatment of cancers and infectious diseases is often hampered by a high degree of variability in the final T cell product and in the limited in vivo function and survival of ex vivo expanded antigen-specific cytotoxic T cells (CTL). This has stimulated interest in development of standardized artificial antigen presenting cells (aAPC) to reliably expand antigen specific CTL. However, for successful immunotherapy the aAPC ex vivo generated CTL must have anti-tumor activity in vivo. Here, we demonstrate that HLA-Ig based aAPC stimulated tumor-specific CTL from human peripheral blood T lymphocytes showed robust expansion and functional activity in a human/SCID mouse melanoma model. HLA-Ig based aAPC expanded CTL were detected in the peripheral blood up to 15 days after transfer. Non-invasive bioluminescence imaging of tumor bearing mice demonstrated antigen dependent localization of transferred CTL to the tumor site. Moreover, adoptive transfer of HLA-Ig based aAPC generated CTL inhibited the tumor growth both in prevention and treatment modes of therapy and was comparable to that achieved by dendritic cell expanded CTL. Thus, our data demonstrate potential therapeutic in vivo activity of HLA-Ig based aAPC expanded CTL to control tumor growth.
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