Immunity, homing and efficacy of allogeneic adoptive immunotherapy for posttransplant lymphoproliferative disorders.
Adoptive immunotherapy using autologous Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes (auto-CTL) can regress posttransplant lymphoproliferative disorders (PTLD). Widespread applicability of auto-CTL remains constrained. Generation is time-consuming, and auto-CTL cannot be established in patients treated with the B-cell depleting antibody rituximab. By contrast, pregenerated allogeneic CTL (allo-CTL) offers immediate accessibility. Allo-CTL has previously shown efficacy in "early" polyclonal- PTLD. We treated three patients with aggressive, advanced monoclonal-PTLD following solid-organ transplantation. All were refractory to at least three prior therapies. Despite HLA disparity, there was negligible toxicity, with early in vivo antiviral efficacy and reconstitution of EBV peptide-specific immunity. Two patients attained complete remission (CR). One remains in CR 17 months following therapy, coincident with persistence of donor-derived tumor targeted EBV-specific CTL; the other died of non-PTLD related pathology. In the third patient, autopsy demonstrated homing of allo-CTL at the tumor site. Larger prospective studies of EBV-specific allo-CTL in PTLD are warranted.
Gandhi
M K
MK
Clinical Immunhaematology Laboratory, Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, Brisbane, Australia. maherG@qimr.edu.au
Wilkie
G M
GM
Dua
U
U
Mollee
P N
PN
Grimmett
K
K
Williams
T
T
Whitaker
N
N
Gill
D
D
Crawford
D H
DH
D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects* / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology; D016040:Lung Transplantation / Q000009:adverse effects* / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000276:immunology* / Q000628:therapy*; D008875:Middle Aged; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology; D019562:Viral Load
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D016201:Receptors, Lymphocyte Homing