Adoptive transfer of EBV-specific T cells results in sustained clinical responses in patients with locoregional nasopharyngeal carcinoma.
Patients with recurrent or refractory Epstein Barr Virus (EBV)-positive nasopharyngeal carcinoma (NPC) continue to have poor outcomes. Our earlier Phase I dose escalation clinical study of 10 NPC patients showed that infusion of EBV-specific cytotoxic T cells (EBV-CTLs) was safe and had antitumor activity. To better define the overall response rate and discover whether disease status, EBV-antigen specificity, and/or in vivo expansion of infused EBV-CTLs predicted outcome, we treated 13 additional NPC patients with EBV-CTLs in a fixed-dose, Phase II component of the study. We assessed toxicity, efficacy, specificity, and expansion of infused CTLs for all 23 recurrent/refractory NPC patients treated on this Phase I/II clinical study. At the time of CTL infusion, 8 relapsed NPC patients were in remission and 15 had active disease. No significant toxicity was observed. Of the relapsed patients treated in their second or subsequent remission, 62% (5/8) remain disease free (at 17 to 75 mo), whereas 48.7% (7/15) of those with active disease had a CR/CRu (33.3%) or PR (15.4%). In contrast to locoregional disease, metastatic disease was associated with an increased risk of disease progression (HR: 3.91, P=0.015) and decreased overall survival (HR: 5.55, P=0.022). Neither the specificity of the infused CTLs for particular EBV antigens nor their measurable in vivo expansion discernibly influenced outcome. In conclusion, treatment of patients with relapsed/refractory EBV-positive NPC with EBV-CTLs is safe and can be associated with significant, long-term clinical benefit, particularly for patients with locoregional disease.
Louis
Chrystal U
CU
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030, USA.
Straathof
Karin
K
Bollard
Catherine M
CM
Ennamuri
Sravya
S
Gerken
Claudia
C
Lopez
Teresita T
TT
Huls
M Helen
MH
Sheehan
Andrea
A
Wu
Meng-Fen
MF
Liu
Hao
H
Gee
Adrian
A
Brenner
Malcolm K
MK
Rooney
Cliona M
CM
Heslop
Helen E
HE
Gottschalk
Stephen
S
D000293:Adolescent; D000328:Adult; D000956:Antigens, Viral / Q000276:immunology; D002277:Carcinoma / Q000175:diagnosis* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D049109:Cell Proliferation; D002648:Child; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D016219:Immunotherapy, Adoptive; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016896:Treatment Outcome
D000956:Antigens, Viral