Large scale expansion of human tumor infiltrating lymphocytes with surface-modified stimulator cells for adoptive immunotherapy.
Expansion of tumor infiltrating lymphocytes (TIL) in vitro is hampered by several factors, including a limited amount of lymphocytes obtained from different tumors, unknown target antigens and limited supply of antigen-presenting cells (APC) which are generally believed to be essential in the classical way of T cell stimulation and expansion. In approaching these difficulties, we have recently used surface-oxidized allogeneic PBL to stimulate the TIL periodically in the presence of a low dose of rIL-2 (200 IU/ml). TIL derived from 22 (out of 23) tumor specimens could be expanded with 20 -10(7) fold increases over 6-16 weeks to a sufficient amount of 10(9) -10(11) cells for adoptive immunotherapy. In contrast, only 2-100 fold increase were observed in six tumor specimens (out of 23) when 200 IU/ml rIL-2 was used only. The phenotypes, autologous tumor reactivity and cytolytic capability of TIL propagated with surface-oxidized stimulators were similar to those expanded in the presence of IL-2 alone. These data suggest that expanding TIL with surface-modified stimulator cells could be a useful alternative method to obtain a large amount of tumor specific cytolytic T cells for clinical immunotherapeutic use, irrespective of tumor-antigen stimulation and MHC restriction.
Chin
Y
Y
Department of Cancer Research, Dr. L. Willems Institute, Diepenbeek, Belgium.
Janssens
J
J
Smeyers
E
E
Bleus
J
J
Zhang
J
J
Raus
J
J
D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology; D002455:Cell Division; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology
D007376:Interleukin-2; D011994:Recombinant Proteins