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Feasibility Study of Personalized Peptide Vaccination for Advanced Small Cell Lung Cancer
Shinjiro Sakamoto1, Teppei Yamada2, Yasuhiro Terazaki3
1Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan; Cancer Vaccine Center, Kurume University, Kurume, Japan; Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Introduction:
The prognosis of patients with small cell lung cancer (SCLC) remains very poor. Therefore, the development of new therapeutic approaches, including immunotherapies, is desirable.
Patients And Methods:
We conducted a phase II study of personalized peptide vaccination (PPV), in which a maximum of 4 human leukocyte antigen-matched peptides were selected from 31 pooled peptides according to the pre-existing peptide-specific IgG responses before vaccination. The PPV was subcutaneously administered.
Results:
Forty-six patients were enrolled (median age, 63 years; 40 patients were men). Grade 1 (n = 13), 2 (n = 10), or 3 (n = 1) skin reactions at the injection sites were observed; however, no other severe adverse events related to the PPV were observed. The median survival time was 466, 397, 401, and 107 days in the subgroups with 0 (n = 5), 1 (n = 15), 2 (n = 12), and ≥ 3 (n = 14) previous chemotherapy regimens, respectively. Peptide-specific IgG responses to the vaccinated peptides were augmented in 70% and 95% of patients after 1 and 2 vaccination cycles, respectively. The overall survival (OS) of patients with augmented IgG responses to a greater number of nonvaccinated peptides after the second cycle of vaccination was significantly longer (median survival time, 1237 days vs. 382 days; P = .010). In addition, augmentation of IgG responses specific to 6 peptides, including Lck-derived peptides, was significantly related to better OS (P < .05, in each peptide).
Conclusion:
These results suggest the feasibility of PPV for SCLC patients from the viewpoints of safety, immune boosting, and possible prolongation of OS. Therefore, further evaluation of PPV for advanced SCLC in prospective randomized trials is warranted.