Alloreactivity and anti-tumor activity segregate within two distinct subsets of cytokine-induced killer (CIK) cells: implications for their infusion across major HLA barriers
Open Access
- 9 May 2008
- journal article
- research article
- Published by Oxford University Press (OUP) in International Immunology
- Vol. 20 (7), 841-848
- https://doi.org/10.1093/intimm/dxn042
Abstract
Donor-derived cytokine-induced killer (CIK) can be infused as adoptive immunotherapy after hematopoietic cell transplant (HCT). Promising results were recently reported in HLA-identical HCT, where mild grafts versus host (GVH) events were observed. To extend this strategy across major HLA barriers (e.g. HLA-haploidentical HCT), further studies on CIK cells' alloreactivity are needed. We hypothesized that alloreactivity and anti-tumor activity of CIK cells segregate within two different cell subsets and could consequently be separated according to CD56 and CD3 expression. We tested CIK cells expanded from seven patients who underwent HCT as treatment of metastatic colorectal cancer. We found that CIK cells maintained their alloreactivity across major HLA barriers when tested as bulk population; after CD56-positive selection, anti-tumor activity was restricted to the CD3+/CD56+ cell fraction and alloreactivity versus HLA-mismatched PBMC was restricted to the CD3+/CD56− cell fraction. Bulk CIK cells from engrafted patients did not exhibit alloreactivity in response to host- or donor-derived PBMC, confirming their low potential for GVH across minor HLA barriers. Moreover, we tested if CIK cells expanded from engrafted patients after HCT were as effective as donor-derived ones and could be considered as an alternative option. The expansion rate and tumor cell killing was comparable to that observed in sibling donors. In conclusion, depletion of CD3+/CD56− cells might reduce the risk of GVH without affecting the tumor-killing capacity and could help extending CIK infusions across major HLA barriers. Engrafted patients after HCT could also be considered as an effective alternative option to donor-derived CIK cells.Keywords
This publication has 28 references indexed in Scilit:
- Repeated infusions of donor-derived cytokine-induced killer cells in patients relapsing after allogeneic stem cell transplantation: a phase I studyHaematologica, 2007
- Rapid and massive expansion of cord blood-derived cytokine-induced killer cells: an innovative proposal for the treatment of leukemia relapse after cord blood transplantationBone Marrow Transplantation, 2006
- Allogeneic nonmyeloablative hematopoietic cell transplantation in metastatic colon cancer: tumor-specific T cells directed to a tumor-associated antigen are generated in vivo during GVHDBlood, 2006
- A phase I trial of autologous cytokine-induced killer cells for the treatment of relapsed Hodgkin disease and non-Hodgkin lymphomaTransplantation and Cellular Therapy, 2005
- Allogeneic Lymphocytes Induce Tumor Regression of Advanced Metastatic Breast CancerJournal of Clinical Oncology, 2004
- Role of NKG2D signaling in the cytotoxicity of activated and expanded CD8+ T cellsBlood, 2004
- Adoptive immunotherapy with donor lymphocyte infusions after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioningBlood, 2004
- Graft-versus-leukemia reactions in allogeneic chimerasBlood, 2004
- Reduced-intensity preparative regimen and allogeneic stem cell transplantation for advanced solid tumorsBlood, 2004
- Propagation of large numbers of T cells with natural killer cell markersBritish Journal of Haematology, 1994