Highly oncolytic adherent lymphocytes: therapeutic relevance for leukemia.
We have generated and characterized a highly oncolytic adherent lymphocyte subset (A-LAK) from eight leukemic patients with non-lymphocytic leukemia (NLL) in remission and one NLL patient in relapse. Our studies demonstrated that A-LAK was superior in its oncolytic activity (tested in a 3-h 51Cr release assay) to conventionally prepared (LAK) and non-adherent (NA) IL-2 cultures. No activity was observed by this highly oncolytic subset against normal bone marrow (BM). A-LAK also displayed highest proliferative activity in 7-11 day cultures (5- to 58-fold expansion) in comparison to LAK (0.7- to 2.7-fold) or NA (1.0- to 2.6-fold) cultures. Analysis of phenotype of unseparated, NA and adherent (A-LAK) lymphocytes 24 h after IL-2 activation showed that the A-LAK was composed predominantly of high intensity (bright) CD11a+ (LFA-1) lymphocytes (75 +/- 4.8%) when compared to the other two populations (12 +/- 2.1%). Similarly, A-LAK contained higher proportion of CD11b (CR3 receptor)-positive lymphocytes (39 +/- 2.1%) than unseparated and NA lymphocytes (11 +/- 1.4%). Double marker phenotypic studies showed that A-LAK cultures were heterogeneous and distribution of individual lymphocyte subsets differed among NLL patients. While in A-LAK culture of some patients the CD56+, CD3- natural killer (NK) cell subset was predominant, CD3+, CD56- lymphocyte subset was prevalent in others. Highest A-LAK lytic activity was always correlated with highest NK cell content. Characterization studies (using the complement-depletion technique) showed that independently of the distribution of lymphocytes in A-LAK cultures, CD16+, CD56+, CD3- NK cell subset displayed highest oncolytic effect. CD5+ subset also participated in cytotoxic function. These observations indicated that A-LAK may represent a new therapeutic approach to treatment of leukemia.
Lotzová
E
E
Department of General Surgery, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Savary
C A
CA
Totpal
K
K
Schachner
J
J
Lichtiger
B
B
McCredie
K B
KB
Freireich
E J
EJ
D000328:Adult; D002448:Cell Adhesion; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000627:therapeutic use; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology / Q000473:pathology / Q000637:transplantation*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000628:therapy*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured / Q000473:pathology
D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen