Cytotoxicity of CD56-positive lymphocytes against autologous B-cell precursor acute lymphoblastic leukemia cells

Abstract

Precursor B-lineage acute lymphoblastic leukemia (pre-B ALL) affects hematopoietic development and therefore is associated with immune deficiencies that can be further exacerbated by chemotherapy. It is unclear if and when monoclonal antibodies (mAbs) that stimulate antibody-mediated cellular cytotoxicity (ADCC) can be used for treatment because this depends on the presence of functional effector cells. Here, we used flow cytometry to determine that patient samples at diagnosis, post-induction and relapse contain detectable numbers of CD56+ cells. We were able to selectively expand CD56+ immune effector cells from bone marrow and peripheral blood samples at diagnosis and at various stages of treatment by co-culture with artificial antigen-presenting K562 clone 9.mbIL-21 cells. Amplified CD56+CD3- cells had spontaneous and anti-BAFF-R mAb-stimulated ADCC activity against autologous ALL cells, which could be further enhanced by IL15. Importantly, matched CD56+ effector cells also killed autologous ALL cells grown out from leukemia samples of the same patient, through both spontaneous as well as antibody-dependent cellular cytotoxicity. Since autologous cell therapy will not be complicated by graft-versus-host disease, our results show that expanded CD56+ cells could be applied for treatment of pre-B-ALL without transplantation, or for purging of bone marrow in the setting of autologous bone marrow transplants.

Central nervous system acute lymphoblastic leukemia: role of natural killer cells

“…In addition to exploiting mismatch of NK inhibitory receptors during stem cell transplantation, [60][61][62][63][64][65] direct treatment of ALL with allogeneic or autologous NK cells has been recently proposed. 56,[66][67][68][69][70] Our findings may be important for emerging NK-based therapies of acute leukemias, suggesting the need for additional prophylactic CNS-directed therapy.…”

Cellular therapy: Adoptive immunotherapy with expanded natural killer cells

“…We initially shared the cell line freely for academic use with over 50 investigators worldwide, until several complications with rights and ownership of the cell line precluded further distribution. The original cell line we described (Clone9.mbIL21) proved very effective in propagating NK cells from peripheral blood of normal donors, patients, and cord blood, and a master cell bank (MCB) with full compendial testing for human clinical use was established to generate NK cells for clinical trials …”

Advances in understanding the pathogenesis of CNS acute lymphoblastic leukaemia and potential for therapy

“…Isolated CNS relapse may indicate the presence of anti-ALL autologous NK cells, a finding that may be exploited for therapy (Fei et al, 2015). Isolated CNS relapse may indicate the presence of anti-ALL autologous NK cells, a finding that may be exploited for therapy (Fei et al, 2015).…”