title: Alloreactivity and anti-tumor activity segregate within two distinct subsets of cytokine-induced killer (CIK) cells: implications for their infusion across major HLA barriers.
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.
authors.affiliation: Department of Oncological Sciences, University of Torino Medical School, Torino, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Sangiolo
authors.forename: Emanuela
authors.initials: E
authors.lastname: Martinuzzi
authors.forename: Maja
authors.initials: M
authors.lastname: Todorovic
authors.forename: Katiuscia
authors.initials: K
authors.lastname: Vitaggio
authors.forename: Antonella
authors.initials: A
authors.lastname: Vallario
authors.forename: Noela
authors.initials: N
authors.lastname: Jordaney
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Carnevale-Schianca
authors.forename: Antonio
authors.initials: A
authors.lastname: Capaldi
authors.forename: Massimo
authors.initials: M
authors.lastname: Geuna
authors.forename: Laura
authors.initials: L
authors.lastname: Casorzo
authors.forename: Richard A
authors.initials: RA
authors.lastname: Nash
authors.forename: Massimo
authors.initials: M
authors.lastname: Aglietta
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cignetti
mesh_terms: D000328:Adult; D000368:Aged; D016913:Blood Component Transfusion; D019002:CD56 Antigen / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D003602:Cytotoxicity, Immunologic; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology; D020350:Graft vs Tumor Effect / Q000276:immunology; D006649:Histocompatibility Antigens / Q000097:blood / Q000276:immunology*; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016131:Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D019002:CD56 Antigen; D006649:Histocompatibility Antigens