Selective purging by human interleukin-2 activated lymphocytes of bone marrows contaminated with a lymphoma line or autologous leukaemic cells.
The ability of recombinant interleukin 2 (rIL2) activated lymphocytes (LAK) to purge BM samples contaminated by tumour cells was evaluated. Human BM mononuclear cells were contaminated with 10% of the lymphoma line CA46 and then cultured in liquid medium containing 1000 U/ml of rIL2 and/or LAK autologous to the used BM. At the end of coculture the growth of residual tumour cells and of CFU-GM were evaluated by clonogenic assay. No tumour cell growth was observed in 5/5 independent experiments after 18 h of coculture with LAK. No significant inhibition of CFU-GM growth was also noted. Subsequently, the effect of LAK on BM obtained from four leukaemic patients and contaminated with 20-50% of their own AML and ALL cells was studied using MAb as a tool for identifying leukaemic cells. LAK eliminated 24-78% of contaminating cryopreserved uncultured autologous leukaemic cells. In five cases the BM was contaminated by a low (2%) amount of ALL cells. In these patients the monoclonal heavy chain rearrangement typical of ALL was no longer visible after coculture with LAK. Evidence for selective tumour cytotoxicity by LAK was confirmed by using autologous BM cells as hot and cold targets in a 51Cr release assay. Finally, successful haematologic reconstitution of lethally irradiated BALB/c mice was obtained using syngeneic BM cocultured with LAK. These results support the investigational use of rIL2 and LAK in the treatment of human leukaemia.
Gambacorti-Passerini
C
C
Division of Experimental Oncology, Istituto Nazionale Tumori-Milan, Italy.
Rivoltini
L
L
Fizzotti
M
M
Rodolfo
M
M
Sensi
M L
ML
Castelli
C
C
Orazi
A
A
Polli
N
N
Bregni
M
M
Siena
S
S
D000208:Acute Disease; D000818:Animals; D001853:Bone Marrow / Q000276:immunology*; D016026:Bone Marrow Transplantation; D002051:Burkitt Lymphoma / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004273:DNA, Neoplasm / Q000032:analysis; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology* / Q000627:therapeutic use; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007938:Leukemia / Q000276:immunology* / Q000628:therapy; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured / Q000276:immunology; D014410:Tumor Stem Cell Assay
D004273:DNA, Neoplasm; D007376:Interleukin-2; D011994:Recombinant Proteins