Immunomodulation with dendritic cells and donor lymphocyte infusion converge to induce graft vs neuroblastoma reactions without GVHD after allogeneic bone marrow transplantation.
BACKGROUND
Mounting evidence points to the efficacy of donor lymphocyte infusion (DLI) and immunisation with tumour-pulsed dendritic cells (DC) in generating graft vs leukaemia reactions after allogeneic bone marrow transplantation (BMT). We assessed the efficacy of DLI and DC in generating potent graft vs neuroblastoma tumour (GVT) reactions following allogeneic BMT.


METHODS
Mice bearing congenic (H2K(a)) Neuro-2a tumours were grafted with allogeneic (H2K(b)) T-cell-depleted bone marrow cells. Tumour-pulsed donor DC (DC(Neuro2a)) were inoculated (on day +7) in conjunction with donor (H2K(b)) and haploidentical (H2K(a/b)) lymphocytes.


RESULTS
Murine Neuro-2a cells elicit immune reactions as efficient as B lymphoma in major histocompatibility complex antigen-disparate mice. Lymphopenia induced by conditioning facilitates GVT, and transition to adaptive immunity is enhanced by simultaneous infusion of and DC(Neuro2a) and lymphocytes devoid of graft vs host (GVH) activity (H2K(a/b)). In variance, the efficacy of DC-mediated immunomodulation was diminished by severe graft vs host disease (GVHD), showing mechanistic dissociation and antagonising potential to GVT.


CONCLUSIONS
The GVHD is not a prerequisite to induce GVT reactivity after allogeneic BMT, but is rather detrimental to induction of anti-tumour immunity by DC-mediated immunomodulation. Simultaneous inoculation of tumour-pulsed donor DC and DLI synergise in stimulation of potent GVT reactions to the extent of eradication of established NB tumours.
Ash
S
S
Department of Pediatric Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva 49202, Israel.
Stein
J
J
Askenasy
N
N
Yaniv
I
I
D019264:Adoptive Transfer; D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology*; D002648:Child; D003713:Dendritic Cells / Q000276:immunology*; D005269:Femur; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D020350:Graft vs Tumor Effect / Q000276:immunology*; D006801:Humans; D016867:Immunocompromised Host; D008099:Liver / Q000276:immunology; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion; D008231:Lymphopenia / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009447:Neuroblastoma / Q000276:immunology*; D012867:Skin / Q000276:immunology; D013977:Tibia; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous / Q000276:immunology