期刊
JOURNAL OF IMMUNOTHERAPY
卷 26, 期 3, 页码 222-233出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00002371-200305000-00006
关键词
beads; CD3; CD28; sarcoma; T cells
资金
- NCI NIH HHS [CA82529] Funding Source: Medline
Ligation of TCR and CD28 expressed on T cells via mAbs results in activation of T cells capable of tumor destruction in adoptive immunotherapy. In a murine model, the authors examined in vitro activation conditions utilizing plate-immobilized and bead-conjugated mAbs that bind to CD3 and CD28. Bead-activated tumor-draining lymph node (TDLN) cells demonstrated superior cytokine (IFN-gamma, GM-CSF, IL-2, and IL-10) secretion and mediated tumor regression more efficiently compared with plate-activated cells. The bead-activated TDLN cells had a significantly higher percentage of CD4(+) cells compared with plate-activated cells. On a per-cell basis, positively selected CD4(+) cells activated with bead-coupled or plate immobilized mAbs mediated tumor-specific regression equally. Bead-activated CD4(+) TDLN cells demonstrated significantly higher levels of tumor specific IL-2 secretion compared with plate-activated CD4(+) cells that may provide helper function to CD8(+) effector cells. The antitumor reactivity of bead-activated lymphoid cells depended upon their source. TDLN cells after bead activation were more potent than splenocytes from tumor-bearing hosts in mediating tumor regression in vivo. Bead-activated LN cells and splenocytes from nontumor-bearing hosts demonstrated nonspecific cytokine secretion and minimal efficacy in adoptive immunotherapy. At minimal doses of IL-2, the antitumor reactivity of bead-activated TDLN cells was significantly enhanced. Anti-CD3/anti-CD28 bead activation of tumor-primed T cells represents an efficient method to generate effector cells for immunotherapy.
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