Immunological evaluation of personalized peptide vaccination in refractory small cell lung cancer

Abstract

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 antigenspecific 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 CD3 + CD26+ 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 largerscale, prospective clinical trials. (Cancer Sci 2012; 103: 638-644)

A phase II study of a personalized peptide vaccination for chemotherapy-resistant advanced pancreatic cancer patients

“…As a result, plasma SAA and CRP levels were inversely correlated with OS. These results were expected based on our previous study on PPV (10). These biomarkers are suggested to be important not only in cancer vaccines, but also in other treatment modalities for advanced pancreatic cancers.…”

“…Patients pathologically and/or clinically diagnosed with pancreatic cancer were eligible for inclusion in the present study, when they had failed at least first-line chemotherapy and showed positive IgG responses to at least 2 of the 31 different vaccine candidate peptides as previously reported (10 The peptides for vaccination to individual patients were selected in consideration of the pre-existing host immunity before vaccination, by assessing the titers of IgG specific to each of the 31 different vaccine candidates (10). A maximum of 4 peptides (3 mg/each peptide), which were selected based on the results of HLA typing and peptide-specific IgG titers, in complex with incomplete Freund's adjuvant (Montanide ISA 51; Seppic, Paris, France) were subcutaneously administered once a week for 6 consecutive weeks.…”

“…After washing, the fluorescence on the beads was detected using the Luminex 200 system. The Igs levels were expressed in fluorescence intensity units (FIU) as previously reported (9)(10)(11). Peptide-specificity of IgG against each of the 31 peptides was confirmed (unpublished data).…”

“…We previously devised a new regimen of peptide-based vaccination, named personalized peptide vaccination (PPV), in which vaccine antigens were selected from 31 different pooled peptides, and administered based on both HLA-class IA types and levels of peptide-specific IgG responses before vaccination (7)(8)(9)(10). In our previous clinical trials, immune responses triggered by PPV were well-associated with overall survival (OS) in advanced pancreatic cancer patients under PPV in combination with GEM as the first-line therapy (7,8).…”

Single nucleotide polymorphisms of the haptoglobin gene in non-small cell lung cancer treated with personalized peptide vaccination

“…Patients were subcutaneously injected weekly or bi-weekly with ISA51VG along with ≤4 peptides selected from the 31 peptide candidates. Clinical studies of small cell and non-small cell lung cancers have indicated that PPV does not cause severe side effects but demonstrates potential immunological efficacy to some extent (8,9). However, only a proportion of patients experience clinical benefits from such vaccines.…”