Personalized peptide vaccination in patients with refractory non-small             cell lung cancer.
Since the prognosis of non-small cell lung cancer (NSCLC) remains poor, the development of novel therapeutic approaches, including cancer vaccines, is highly desirable. In the current study, we conducted a phase II study of personalized peptide vaccination (PPV), in which a maximum of 4 peptides were selected based on pre-existing humoral immune responses and administered subcutaneously (weekly for 6 consecutive weeks and bi-weekly thereafter) in refractory NSCLC patients. Forty-one refractory NSCLC patients (4 stage IIIb, 22 stage IV and 15 recurrent), who had failed to respond to chemotherapy and/or targeted therapy (median number of regimens, 3; median duration, 10 months), were enrolled. Median overall survival (OS) was 304 days with a one-year survival rate of 42% in the enrolled patients. The main toxicity of PPV was skin reactions at the injection sites, but no serious adverse events were observed. In order to identify potential biomarkers for predicting OS, pre-vaccination and post-vaccination clinical findings and laboratory data were retrospectively assessed and evaluated by multivariate Cox regression analysis. Among the pre-vaccination factors examined, high C-reactive protein (CRP) level was a significant predictor of unfavorable OS [hazard ratio (HR)=10.115, 95% confidence interval (CI)=2.447-41.806, P=0.001]. Among the post-vaccination factors, high CRP level and low frequency of CD3⁺CD26⁺ cells were significant predictors of unfavorable OS (HR=23.127, 95% CI=2.919-183.233, P=0.003; HR=0.952, 95% CI=0.917-0.989, P=0.012). Taken together, our results suggest the feasibility of PPV for the treatment of refractory NSCLC. Evaluation of the identified factors before or at an early stage of vaccination could be potentially useful for selecting NSCLC patients who would likely have better prognosis following PPV.
Department of Surgery, Kurume University School of Medicine,                     Kurume, Fukuoka, Japan.
Koichi
K
Yoshiyama
Yasuhiro
Y
Terazaki
Satoko
S
Matsueda
Shigeki
S
Shichijo
Masanori
M
Noguchi
Akira
A
Yamada
Takashi
T
Mine
Tetsuya
T
Ioji
Kyogo
K
Itoh
Kazuo
K
Shirouzu
Tetsuro
T
Sasada
Shinzo
S
Takamori
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D017252:CD3 Complex / Q000097:blood; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016207:Cytokines / Q000097:blood; D018819:Dipeptidyl Peptidase 4 / Q000097:blood; D019008:Drug Resistance, Neoplasm; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D056724:Immunity, Humoral; D007115:Immunization Schedule; D018836:Inflammation Mediators / Q000097:blood; D007279:Injections, Subcutaneous; D007564:Japan; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D057285:Precision Medicine; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000276:immunology / Q000627:therapeutic use
D014408:Biomarkers, Tumor; D017252:CD3 Complex; D019496:Cancer Vaccines; D016207:Cytokines; D018836:Inflammation Mediators; D022223:Vaccines, Subunit; D002097:C-Reactive Protein; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4