Rapid induction of cytolytic T cells via CD28 stimulation for cellular immunotherapy.
One approach to adoptive cancer immunotherapy is based on the use of bispecific monoclonal antibodies (mAb) capable to redirect ex vivo generated cytolytic T lymphocytes (CTL) onto tumour cells. The efficiency of the CD28 T-cell activation pathway to induce CD3-dependent cytolytic activity was investigated while avoiding modulation of the TCR/CD3 complex needed for targeting by bispecific mAb. When used e.g. in conjunction with anti-CD2 antibodies or diacylglycerol derivatives, the in vitro stimulation of T cells with anti-CD28 mAb resulted within 36 h in high levels of CD3-dependent cytolysis (tested on a FcR+ target in the presence of anti-CD3 mAb) and sustained lymphokine production, such as TNF alpha, IFN gamma and IL-2, which may affect tumour growth when delivered locally by the transferred T cells. Rapid activation may reduce costly in vitro procedures, preserve homing capacities of retransfused T cells, and thus facilitate implementation of clinical trials based on the use of bispecific antibodies.
Blum
S
S
Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland.
Milesi
R
R
Tratkiewicz
J
J
Olive
D
D
Gallati
H
H
Cerottini
J C
JC
von Fliedner
V
V
D018033:Antibodies, Bispecific / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D003602:Cytotoxicity, Immunologic; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D008213:Lymphocyte Activation; D011493:Protein Kinase C / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines; D004075:Diglycerides; C044295:1,2-dioctanoylglycerol; D011493:Protein Kinase C