Feasibility Study of Personalized Peptide Vaccination for Advanced Small Cell Lung Cancer

Clin Lung Cancer. 2017 Nov;18(6):e385-e394. doi: 10.1016/j.cllc.2017.03.011. Epub 2017 Mar 24.

Abstract

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.

Keywords: Epitope spreading; IgG; Lck; PPV; SCLC.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / immunology
  • Feasibility Studies
  • Female
  • Humans
  • Immunoglobulin G / immunology
  • Immunotherapy / methods*
  • Injections, Subcutaneous
  • Lung Neoplasms / immunology
  • Lung Neoplasms / therapy*
  • Male
  • Middle Aged
  • Peptides / administration & dosage*
  • Peptides / immunology
  • Precision Medicine
  • Prognosis
  • Small Cell Lung Carcinoma / immunology
  • Small Cell Lung Carcinoma / therapy*
  • Survival Rate

Substances

  • Cancer Vaccines
  • Immunoglobulin G
  • Peptides