Activation and expansion of tumour-infiltrating lymphocytes by anti-CD3 and anti-CD28 monoclonal antibodies.
Cytotoxic T lymphocytes from healthy donors can be expanded to high numbers from the peripheral blood using combinations of anti-CD3 and anti-CD28 monoclonal antibodies (mAb). We investigated whether these antibodies could also be used to induce outgrowth of tumour-infiltrating lymphocytes (TIL) from tumour tissue. In the initiation phase of TIL culture immobilized anti-CD3 antibodies together with anti-CD28 mAb and low-dose interleukin-2 induced a rapid expansion of T cells from various human tumour tissues. The cultured cells showed high levels of cytotoxic T lymphocyte activity, but low levels of lymphokine-activated killer cell activity were generated. This study shows that TIL can be efficiently expanded from tumour tissue by combinations of anti-CD3 and anti-CD28 antibodies. This protocol for cell expansion in vitro may substantially reduce the time required to reach sufficient numbers of TIl for re-infusion to the patient.
Nijhuis
E W
EW
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, University of Amsterdam.
vd Wiel-van Kemenade
E
E
Figdor
C G
CG
van Lier
R A
RA
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D018106:CD28 Antigens; D017252:CD3 Complex; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell