Adoptive transfer of allogeneic Epstein-Barr virus (EBV)-specific cytotoxic T cells with in vitro antitumor activity boosts LMP2-specific immune response in a patient with EBV-related nasopharyngeal carcinoma.
BACKGROUND
The outcome of patients with nasopharyngeal carcinoma (NPC) presenting as advanced-stage disease or failing conventional radio-chemotherapy is poor. Thus, additional forms of effective, low-toxicity treatment are warranted to improve NPC prognosis. Since NPC is almost universally associated with Epstein-Barr virus (EBV), cellular immunotherapy with EBV-specific cytotoxic T lymphocytes (CTLs) may prove a successful treatment strategy. Patient and methods A patient with relapsed NPC, refractory to conventional treatments, received salvage adoptive immunotherapy with EBV-specific CTLs reactivated ex vivo from a human leukocyte antigen-identical sibling. EBV-specific immunity, as well as T-cell repertoire in the tumor, before and after immunotherapy, was evaluated.


RESULTS
CTL transfer was well tolerated, and a temporary stabilization of disease was obtained. Moreover, notwithstanding the short in-vivo duration of allogeneic CTLs, immunotherapy induced a marked increase of endogenous tumor-infiltrating CD8+ T lymphocytes, and a long-term increase of latent membrane protein 2-specific immunity.


CONCLUSIONS
Preliminary data obtained in this patient indicate that EBV-specific CTLs are safe, may exert specific killing of NPC tumor cells in vitro, and induce antitumor effect in vivo.
Comoli
P
P
Laboratory of Transplant Immunology and Pediatric Hematology/Oncology, IRCCS Policlinico S. Matteo, Pavia, Italy. pcomoli@smatteo.pv.it
De Palma
R
R
Siena
S
S
Nocera
A
A
Basso
S
S
Del Galdo
F
F
Schiavo
R
R
Carminati
O
O
Tagliamacco
A
A
Abbate
G F
GF
Locatelli
F
F
Maccario
R
R
Pedrazzoli
P
P
D000328:Adult; D000956:Antigens, Viral / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D016219:Immunotherapy, Adoptive; D008297:Male; D009303:Nasopharyngeal Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D009375:Neoplasms, Glandular and Epithelial / Q000276:immunology* / Q000473:pathology / Q000628:therapy* / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation; D014184:Transplantation, Homologous; D014763:Viral Matrix Proteins / Q000276:immunology*; D017735:Virus Latency
D000956:Antigens, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins