[Selective depletion of alloreactive T cells and study of anti-tumor activity of specific T cell clones in patients with leukemia].
BACKGROUND
Graft-versus-host disease (GVHD) is a severe complication of allogeneic transplantation of hematopoietic stem cells. Donor T cells play a major role in GVHD leading to the host tissue damage, mainly the skin, liver, and gastrointestinal tract. A selective depletion using an anti-CD25 immunotoxin can eliminate harmful alloreactive T cells while preserving other donor T cells with antileukemic and antiinfectious reactivity.


METHODS
We performed 15 mixed lymphocyte reactions with clinical specimens from 12 patients with various types of leukemia (7x AML, 3x ALL, 1x CML, 1x CLL) and PBMC from 15 healthy volunteers from Transfusive station FN Brno Bohunice.


RESULTS
In our experiments we have demonstrated, that antileukemic (GVL) effect of donor, especially CD4+ T cells was well preserved (7.46%), while unfavourable alloreactive (GVH) reaction of donor T cells was completely removed. The graft-versus-host (GVH) reactivation of donor cells was negligible ever after repeated stimulation with irradiated patient's PBMC.


CONCLUSIONS
We have shown that anti-CD25 immunotoxin (IT), RFT5-SMPT-dgA, launched against alpha chain for human interleukin 2 (IL-2), led to long-term selective depletion of alloreactive donor T cell clones while their antileukemic activity was well preserved. Base on our results the clinical phase I/II study was designed. This study was initiated in year 2007 in three clinical centers in Czech Republic.
Matejková
E
E
Univerzitní Centrum Bunecné Imunoterapie, Masarykova Univerzita, Brno. ematej@med.muni.cz
Ocadlíková
D
D
Smejkalová
J
J
Muzíkova
J
J
Raida
L
L
Tousovská
K
K
Pacasová
R
R
Nenicková
M
M
Tesarová
E
E
Sterba
J
J
Indrák
K
K
Michálek
J
J
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal; D002648:Child; D002999:Clone Cells; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D018796:Immunoconjugates; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007938:Leukemia / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion; D008875:Middle Aged; D012276:Ricin; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D053645:Interleukin-2 Receptor alpha Subunit; C114847:RFT5-SMPT-dgA immunotoxin; D012276:Ricin