Short-term ex vivo activation of splenocytes with anti-CD3 plus IL-2 and infusion post-BMT into mice results in in vivo expansion of effector cells with potent anti-lymphoma activity.
We investigated the proliferation and therapeutic utility of anti-CD3 activated splenocytes infused into mice following BMT. Using congenic mouse strains we demonstrated that splenocytes activated briefly ex vivo with anti-CD3 plus IL-2 (T-activated killer cells or T-AK) and infused intravenously following BMT had a greater expansion in blood, spleen and BM compared with splenocytes stimulated with IL-2 alone. T-AK cells recovered from blood, spleen and BM consisted predominantly of CD8+ T cells. A single infusion of T-AK cells given on day +1 post-syngeneic BMT and sustained in vivo with liposomal encapsulated IL-2, significantly increased survival of mice with BDL-2 lymphoma when compared with mice receiving saline and those treated with IL-2 liposomes alone. The anti-tumor effect of T-AK cells was significantly enhanced when IL-2 was given by continuous infusion compared with bolus injections. Depletion studies confirmed that the CD8+ T-AK cells were mainly responsible for the anti-tumor effect against BDL-2 lymphoma. Our findings demonstrate that brief ex vivo activation of splenocytes with anti-CD3 plus IL-2 results in in vivo proliferation of effector cells with potent anti-tumor activity following BMT.
Department of Pediatrics, University of Minnesota, Minneapolis 55455.
E
E
Katsanis
Z
Z
Xu
P M
PM
Anderson
B B
BB
Dancisak
M A
MA
Bausero
D J
DJ
Weisdorf
B R
BR
Blazar
A C
AC
Ochoa
D000818:Animals; D016026:Bone Marrow Transplantation; D017252:CD3 Complex / Q000276:immunology*; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D005260:Female; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008081:Liposomes; D008213:Lymphocyte Activation; D008223:Lymphoma / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
D017252:CD3 Complex; D007376:Interleukin-2; D008081:Liposomes