Phase II Clinical Trial of Multiple Peptide Vaccination for Advanced Head and Neck Cancer Patients Revealed Induction of Immune Responses and Improved OS

Abstract

Purpose: The peptides derived from ideal cancer-testis antigens, including LY6K, CDCA1, and IMP3 (identified using genome-wide cDNA microarray analyses), were used in immunotherapy for head and neck squamous cell cancer (HNSCC). In this trial, we analyzed the immune response to and safety and efficacy of vaccine therapy.Experimental Design: A total of 37 patients with advanced HNSCC were enrolled in this trial of peptide vaccine therapy, and the OS, PFS, and immunologic response were evaluated using enzyme-linked ImmunoSpot (ELISPOT) and pentamer assays. The peptides were subcutaneously administered weekly with IFA. The primary endpoints were evaluated on the basis of differences between HLA-A Ã 2402-positive [A24(þ)] patients treated with peptide vaccine therapy and -negative [A24(À)] patients treated without peptide vaccine therapy among those with advanced HNSCC.Results: Our cancer vaccine therapy was well tolerated. The OS of the A24(þ) vaccinated group (n ¼ 37) was statistically significantly longer than that of the A24(À) group (n ¼ 18) and median survival time (MST) was 4.9 versus 3.5 months, respectively; P < 0.05. One of the patients exhibited a complete response. In the A24(þ) vaccinated group, the ELISPOT assay identified LY6K-, CDCA1-, and IMP3-specific CTL responses in 85.7%, 64.3%, and 42.9% of the patients, respectively. The patients showing LY6K-and CDCA1-specific CTL responses demonstrated a longer OS than those without CTL induction. Moreover, the patients exhibiting CTL induction for multiple peptides demonstrated better clinical responses.Conclusions: The immune response induced by this vaccine may improve the prognosis of patients with advanced HNSCC.

IMP3 and p16 expression in squamous cell carcinoma of the head and neck: A comparative immunohistochemical analysis

“…A new Phase II study using IMP3 as a vaccination therapy in patients with HNSCC showed an immune response and an improved overall survival (39). These developments underline the relevance of further in-depth studies in the future to determine the exact roles of IMP3 in different molecular and etiological subtypes of HNSCC.…”

“…A previous study showed promising results in support of the use of IMP3 as a potential vaccination therapy in patients with HNSCC (39). A new Phase II study using IMP3 as a vaccination therapy in patients with HNSCC showed an immune response and an improved overall survival (39).…”

Cancer vaccine therapy based on peptides

“…The targeting oncogenic antigens can avoid the immune escape of cancer cells by lacking these proteins [22,23] . Epitope peptides of several oncoantigens such as kinesin family member 20A (KIF20A), lymphocyte antigen 6 complex locus K (LY6K), DEP domain-containing 1 (DEPDC1), forkhead box M1 (FOXM1), cell division cycleassociated 1 (CDCA1), cadherin 3/P-cadherin (CDH3), insulin-like growth factor-II mRNAbinding protein 3 (IMP-3) and others have been developed for clinical trials [24][25][26][27][28][29][30][31][32][33] .…”

A Tumor Mitochondria Vaccine Protects against Experimental Renal Cell Carcinoma

“…To verify the functional relevance of the identified TAMA candidates, we designed peptides for vaccination or for in vitro restimulation and included these mutations (38). For each TAMA, three peptides were generated, each 15 aa in length and overlapping by 5 aa, including the mutation (39).…”