Vaccination of patients with advanced non-small-cell lung cancer with an optimized cryptic human telomerase reverse transcriptase peptide.
OBJECTIVE
To evaluate the immunological and clinical response as well as the safety of the optimized peptide telomerase reverse transcriptase p572Y (TERT572Y) presented by HLA-A*0201 in patients with advanced non-small-cell lung cancer (NSCLC).


METHODS
Twenty-two patients with advanced NSCLC and residual (n = 8) or progressive disease (PD; n = 14) following chemotherapy and/or radiotherapy received two subcutaneous injections of the optimized TERT572Y peptide followed by four injections of the native TERT572 peptide administered every 3 weeks. Peptide-specific immune responses were monitored by enzyme-linked immunosorbent spot assay and/or TERT572Y pentamer staining.


RESULTS
Twelve (54.5%) of 22 patients completed the vaccination program. Toxicity consisted primarily of local skin reactions. TERT572-specific CD8+ cells were detected in 16 (76.2%) of 21 patients after the second vaccination, and 10 (90.9%) of 11 patients after the sixth vaccination. Stable disease (SD) occurred in eight (36.4%) of 22 vaccinated patients, with three (13.6%) having had PD before entering the study. The median duration of SD was 11.2 months. After a median follow-up of 10.0 months, patients with early developed immunological response (n = 16) had a significantly longer time to progression and overall survival (OS) than nonresponders (n = 5; log-rank tests P = .046 and P = .012, respectively). The estimated median OS was 30.0 months (range, 2.8 to 40.0 months) and 4.1 months (range, 2.4 to 10.9 months) for responders and nonresponders, respectively.


CONCLUSIONS
TERT572Y peptide vaccine is well tolerated and effective in eliciting a specific T cell immunity. Immunological response is associated with prolonged survival. These results are encouraging and warrant further evaluation in a randomized study.
Bolonaki
Irini
I
Department of Transfusion Medicine, University General Hospital of Heraklion, Heraklion, Crete, Greece.
Kotsakis
Athanassios
A
Papadimitraki
Elsa
E
Aggouraki
Despoina
D
Konsolakis
George
G
Vagia
Aphrodite
A
Christophylakis
Charalambos
C
Nikoloudi
Irini
I
Magganas
Elefterios
E
Galanis
Athanassios
A
Cordopatis
Paul
P
Kosmatopoulos
Kostas
K
Georgoulias
Vassilis
V
Mavroudis
Dimitris
D
D000368:Aged; D019496:Cancer Vaccines; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015234:HLA-A Antigens / Q000235:genetics*; D015789:HLA-A2 Antigen; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry*; D019098:Telomerase / Q000737:chemistry* / Q000235:genetics* / Q000627:therapeutic use; D016896:Treatment Outcome
D019496:Cancer Vaccines; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D010455:Peptides; D019098:Telomerase; C521181:telomerase reverse transcriptase p572Y, human