Phase I study of a new cancer vaccine of ten mixed peptides for advanced cancer patients

Abstract

A phase I study of a new cancer vaccine (KRM‐10), consisting of a mixture of 10 different short peptides, was conducted for patients with advanced gastrointestinal cancers. Primary or secondary endpoints included the dose‐limiting toxicity (DLT), or safety and immune responses, respectively. Peptide‐specific cytotoxic T lymphocytes (CTL) and immunoglobulin G (IgG), together with soluble inflammatory factors, were measured before and after vaccination. Twenty‐one patients were vaccinated with KRM‐10 at dose levels of 10 (n = 6), 20 (n = 8) or 30 mg (n = 7) of peptides every week for 6 weeks. No DLT were observed in the dose range evaluated. Common treatment‐related adverse events were a grade 1 injection site reaction in 15 patients, and fever in three patients (grade 1 in two patients and grade 2 in one patient). CTL activity to at least one peptide at the time of the third and sixth vaccination increased in 2 and 3 of 6 (10 mg), 2 of 8 and 4 of 6 (20 mg), or 2 and 1 of 6 (30 mg) patients, respectively. IgG levels, at the third and sixth vaccination, were also increased in 1 and 1 of 6 (10 mg), 2 of 8 and 4 of 6 (20 mg), or 1 and 3 of 6 (30 mg) patients, respectively. The KRM‐10 vaccine consisting of 20 mg of peptides was determined as the optimal dose for a coming phase II trial because of its safety, and also for demonstrating the most potent activity for augmenting the immune response of the three doses tested. This trial was registered at the UMIN Clinical Trials Registry as UMIN000008820.

Phase 1 study of OCV‐C02, a peptide vaccine consisting of two peptide epitopes for refractory metastatic colorectal cancer

“…Also, there was no significant deviation from baseline value/condition in other safety variables that were assessed in the present study. This is consistent with the safety outcomes that were reported in other clinical studies of peptide vaccines that are currently under development, and TEAE observed here were similar to those reported in the other studies . In addition, serious adverse reactions as a result of peptide vaccine therapies are very rare .…”

“…This is consistent with the safety outcomes that were reported in other clinical studies of peptide vaccines that are currently under development, and TEAE observed here were similar to those reported in the other studies. (12,16,(20)(21)(22) In addition, serious adverse reactions as a result of peptide vaccine therapies are very rare. (9) Thus, it can be suggested that OCV-C02 at 0.3-6 mg/body has a well-tolerable profile with no major toxic effects.…”

Personalized Kampo Medicine Facilitated Both Cytotoxic T Lymphocyte Response and Clinical Benefits Induced by Personalized Peptide Vaccination for Advanced Esophageal Cancer

“…The expression levels of the 15 vaccine antigens that code the peptides were examined by immunohistochemical staining in tumor tissues from nonvaccinated esophageal ( n = 10) cancer patients. Detailed methods including the antibodies used for IHC were previously described [ 6 , 7 , 9 , 10 ].…”

“…CTL activity specific to each of the HLA-matched vaccinated peptides was evaluated by IFN- γ ELISPOT assay using PBMCs as reported previously [ 5 – 10 ]. As nonvaccinated peptides, a mixture of virus-derived CTL epitopes (CEF peptides, Mabtech) was provided for the assay.…”

“…The cut-off level was set as 10 IFN γ -spots per 10 5 PBMCs. If the spot numbers, in response to the corresponding peptide in postvaccination PBMCs, were more than twofold higher than those in prevaccination PBMCs, the changes were considered to represent positive immune responses, as reported previously [ 5 – 10 ]. The changes were also considered to be positive if the spot numbers that were under 10 in the prevaccination samples became detectable after the vaccination.…”