Open AccessImmunological evaluation of personalized peptide vaccination in refractory small cell lung cancer
Author(s) -
Terazaki Yasuhiro,
Yoshiyama Koichi,
Matsueda Satoko,
Watanabe Noriko,
Kawahara Akihiko,
Naito Yoshiki,
Suekane Shigetaka,
Komatsu Nobukazu,
Ioji Tetsuya,
Yamada Akira,
Mine Takashi,
Terasaki Mizuhiko,
Itoh Kyogo,
Takamori Shinzo,
Sasada Tetsuro
Publication year - 2012
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2012.02202.x
Subject(s) - medicine , vaccination , hazard ratio , antigen , refractory (planetary science) , immunology , lung cancer , peptide vaccine , immune system , human leukocyte antigen , chemotherapy , gastroenterology , confidence interval , oncology , epitope , biology , astrobiology
Since the prognosis of small cell lung cancer ( SCLC ) remains poor, development of new therapeutic approaches, including immunotherapies, would be desirable. In the current study, to evaluate immunological responses in refractory SCLC patients, we conducted a small scale phase II clinical trial of personalized peptide vaccination ( PPV ), in which vaccine antigens are selected based on pre‐existing host immunity. Ten refractory SCLC patients, who had failed to respond to chemo‐ and/or chemoradiotherapies (median number of regimens, 2.5; median duration, 20.5 months), were enrolled. A maximum of four human leukocyte antigen (HLA) ‐matched peptides showing higher antigen‐specific humoral responses were subcutaneously administered (weekly for six consecutive weeks and then bi‐weekly thereafter). PPV was terminated before the 3rd administration in four patients because of rapid disease progression, whereas the remaining six patients completed at least one cycle (six times) of vaccinations. Peptide‐specific immunological boosting was observed in all of the six patients at the end of the first cycle of vaccinations, with their survival time of 25, 24.5 (alive), 10 (alive), 9.5, 6.5, and 6 months. Number of previous chemotherapy regimens and frequency of CD 3 + CD 26 + cells in peripheral blood were potentially prognostic in the vaccinated patients (hazard ratio [ HR ] = 2.540, 95% confidence interval [ CI ] = 1.188–5.431, P = 0.016; HR = 0.941, 95% CI = 0.878–1.008, P = 0.084; respectively). Based on the feasible immune responses in refractory SCLC patients who received at least one cycle (six times) of vaccinations, PPV could be recommended for a next stage of larger‐scale, prospective clinical trials. ( Cancer Sci 2012; 103: 638–644)