Antitumor reactivity of anti-CD3/anti-CD28 bead-activated lymphoid cells: implications for cell therapy in a murine model.
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.
Ito
Fumito
F
The Division of Surgical Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, USA.
Carr
Abbey
A
Svensson
Hakan
H
Yu
Jiyun
J
Chang
Alfred E
AE
Li
Qiao
Q
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D018106:CD28 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D005260:Female; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000627:therapeutic use; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D012513:Sarcoma, Experimental / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017252:CD3 Complex; D007376:Interleukin-2; D007371:Interferon-gamma