Phase I clinical trial of survivin‐derived peptide vaccine therapy for patients with advanced or recurrent oral cancer

Abstract

Survivin, a member of the inhibitor of apoptosis protein (IAP) family, is abundantly expressed in most malignancies, but is hardly detectable in normal adult tissues. Previously we have identified a human leukocyte antigen (HLA)-A24-restricted antigenic peptide, survivin-2B80-88 (AYACNTSTL), recognized by CD8 + cytotoxic T lymphocytes (CTL). Survivin-2B80-88-specific CTL were induced efficiently from peripheral blood mononuclear cells (PBMC) of oral cancer patients after stimulation with the peptide in vitro. We conducted a phase I clinical study to evaluate the safety and the efficacy of survivin-2B80-88 peptide vaccination in HLA-A24-positive patients with advanced or recurrent oral cancer. The vaccines were given subcutaneously or intratumorally six times at 14-day intervals. Eleven patients were enrolled and 10 patients completed the vaccination protocol. No adverse events were observed in any patients. In two patients, the levels of serum squamous cell carcinoma (SCC) antigen decreased transiently during the period of vaccination. Tumor regression that was compatible with a partial response (PR) was noted in one patient. The remaining nine patients experienced progressive disease (PD). Immunologically, an increase of the peptide-specific CTL frequency was detected in six of the eight patients evaluated by HLA-A24/peptide tetramer analysis. The present clinical trial revealed that survivin-2B peptide vaccination was safe and had therapeutic potential for oral cancer patients. However, subsequent clinical trials in combination with various adjuvant drugs will be required to improve the immunological and therapeutic efficacy. This trial was registered with University Hospital Medical Information Network (UMIN) number UMIN000000976. (Cancer Sci 2011; 102: 324-329) O ral cancer consistently ranks as one of the 10 most frequently diagnosed cancers worldwide.(1) It encompasses a range of malignant tumors arising from various diverse and complex structures that have major physiological and aesthetic importance. For most early stage oral cancers, high cure rates are achieved with either surgery or definitive irradiation and both speech and swallowing functions can often be preserved. On the other hand, locally advanced or recurrent oral cancers are usually treated with combination therapy consisting of either surgery followed by postoperative chemoradiation or chemoradiation with surgical salvage if needed. However, most patients remain at high risk for locoregional recurrence and distant metastasis.(2) Therefore, advances in new therapeutic modalities such as tumor-specific immunotherapy for patients with locally advanced or recurrent oral cancers are urgently needed.A large number of tumor-associated antigens have been identified from melanomas and other cancers, and clinical trials of peptide-based immunotherapy have been carried out. Melanoma antigen peptides were the first to be tested in phase I and phase II studies for active immunization of metastatic melanoma patients.(3,4) During the first stage of the ...

Efficient inhibition of ovarian cancer by degradable nanoparticle-delivered survivin T34A gene

“…[29][30][31] Currently, several survivintargeted drugs have successfully reached Phase I or II in human clinical trials. 32,33 Accordingly, many therapeutic strategies targeting the survivin gene have been developed for cancer treatment. 34 For example, Vivas-Mejia et al have used small interfering RNA to target survivin for ovarian cancer, which could suppress the expression of survivin.…”

Prognostic and biological significance of survivin expression in patients with diffuse large B-cell lymphoma treated with rituximab-CHOP therapy

“…Survivin-2B80-88 (refs. [74][75][76] and Survivin-2B 77 have shown the safety and therapeutic potential in cancers, such as breast cancer, colorectal cancer, and gastric cancer. SVN53-67/M57 (SurVaxM) has demonstrated its clinical potential in the treatment of gliomas and, more importantly, this vaccine contains multiple HLA epitopes that may be applicable to a large patient population.…”

Phase I Clinical Trial of Peptide Vaccination with KIF20A and VEGFR1 Epitope Peptides in Patients with Advanced Pancreatic Cancer

“…Among the Japanese population, 60.8% share a common HLA-A*2402 allele [27]. Although this trial had a small number of patients, we did recognize that overall survival was prolonged in the HLA-A*2402-positive group in comparison with the HLA-A*2402-negative group (MST 6.0 months vs. 2.3 months, p=0.0373: Figure1).…”