title: Adoptive cellular therapy using cells enriched for NKG2D+CD3+CD8+T cells after autologous transplantation for myeloma.
abstract: The number of circulating lymphocytes on day 15 after transplantation correlates with improved survival in patients with myeloma, but the lymphocyte subset responsible is unknown. NKG2D is a natural killer (NK) cell activating receptor that mediates non-MHC restricted and TCR-independent cell lysis. Our preliminary results indicate that CD3(+)CD8(+) T cells expressing NKG2D may be a critical lymphocyte population. A phase II trial examined the feasibility of infusing ex vivo-expanded cells enriched for NKG2D(+)CD3(+)CD8(+) T cells at weeks 1, 2, 4, and 8 after an autologous transplantation. In addition, low-dose IL-2 (6 × 10(5) IU/m(2)/day) was administered for 4 weeks, beginning on the day of transplantation. Twenty-three patients were accrued and 19 patients are evaluable. There were no treatment-related deaths. All patients completed their course of IL-2 and demonstrated normal engraftment. When compared with patients with myeloma who underwent transplantation not receiving posttransplantation immune therapy, the treated patients demonstrated an increase in the number of circulating NKG2D(+)CD3(+)CD8(+) T cells/μL (P < .004), CD3(+)CD8(+) T cells/μL (P < .04), CD3(+)CD8(+)CD56(+) T cells/μL (P < .004), and NKG2D(+)CD3(-)CD56(+) T cells/μL (P < .003). Myeloma cell-directed cytotoxicity by the circulating mononuclear cells increased after transplantation (P < .002). When compared to posttransplantation IL-2 therapy alone in this patient population, the addition of cells enriched for NKG2D(+)CD3(+)CD8(+) T cells increased tumor-specific immunity, as demonstrated by enhanced lysis of autologous myeloma cells (P = .02). We postulate that this regimen that increased the number and function of the NKG2D(+)CD3(+)CD8(+) T cells after transplantation may improve clinical outcomes by eliminating residual malignant cells in vivo.
authors.affiliation: Blood and Marrow Transplant Program, Dartmouth Hitchcock Medical Center, Dartmouth Medical School and Norris Cotton Cancer Center, Lebanon, New Hampshire 03756, USA. Kenneth.Meehan@hitchcock.org
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Meehan
authors.forename: Laleh
authors.initials: L
authors.lastname: Talebian
authors.forename: Tor D
authors.initials: TD
authors.lastname: Tosteson
authors.forename: John M
authors.initials: JM
authors.lastname: Hill
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Szczepiorkowski
authors.forename: Charles L
authors.initials: CL
authors.lastname: Sentman
authors.forename: Marc S
authors.initials: MS
authors.lastname: Ernstoff
mesh_terms: D000293:Adolescent; D019264:Adoptive Transfer; D000328:Adult; D000368:Aged; D017252:CD3 Complex; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D055655:NK Cell Lectin-Like Receptor Subfamily K; D036102:Peripheral Blood Stem Cell Transplantation; D014182:Transplantation, Autologous
chemical_list: D017252:CD3 Complex; C508594:IL2 protein, human; D007376:Interleukin-2; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K