In vitro and in vivo susceptibility of human leukemic cells to lymphokine activated killer activity.
The susceptibility of human myeloid and lymphoid leukemic blasts to the lytic action of recombinant interleukin-2 (rIL-2)-generated lymphokine activated killer (LAK) cells was analyzed. With the exception of the K562 cell line, all 9 leukemic cell lines tested were resistant to the natural killer activity of freshly isolated peripheral blood lymphocytes (PBL) from healthy donors but were susceptible to the lytic action of PBL cultured for 3 days in the presence of rIL-2. Of the 32 primary myeloid and lymphoid acute leukemia samples investigated, the great majority were natural killer cell-resistant but were variably sensitive to LAK effectors. Variations in LAK activity were observed according to the donor of PBL, while little or no difference was documented in the capacity to elicit LAK activity of PBL cultured with 100 or 1,000 U of rIL-2/ml. Pretreatment of the leukemic target cells with neuraminidase did not increase substantially their sensitivity to LAK activity. LAK cells generated from the PBL of patients at the onset of the disease or in complete clinicohematological remission lysed Raji cells as efficiently as normal LAK effectors. Finally, LAK cells were capable of abrogating the tumor growth in nude mice of a human leukemic T cell line. These findings demonstrate the susceptibility in vitro and in vivo of human leukemic blasts to the lytic effect of LAK cells and point to a possible clinical exploitment of this new form of adoptive immunotherapy in the management of acute leukemia.
Fierro
M T
MT
Dipartimento di Scienze Biomediche e Oncologia Umana, University of Torino, Italy.
Liao
X S
XS
Lusso
P
P
Bonferroni
M
M
Matera
L
L
Cesano
A
A
Lista
P
P
Arione
R
R
Forni
G
G
Foa
R
R
D000818:Animals; D001402:B-Lymphocytes; D002460:Cell Line; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000502:physiology*; D007942:Leukemia, Experimental / Q000473:pathology / Q000628:therapy*; D007951:Leukemia, Myeloid / Q000473:pathology / Q000628:therapy*; D011994:Recombinant Proteins / Q000494:pharmacology*; D013601:T-Lymphocytes
D007376:Interleukin-2; D011994:Recombinant Proteins