Abstract
Cancer immunotherapy including vaccine therapy is a promising modality for cancer treatment, but few patients show its clinical benefits currently. The identification of biomarkers that can identify patients who will benefit from cancer immunotherapy is thus important. Here, we investigated the potential utility of the circulating cell-free DNA (cfDNA) integrity—a ratio of necrotic cell-derived, longer DNA fragments versus apoptotic cell-derived shorter fragments of Alu gene—as a biomarker of vaccine therapy for patients with ovarian cancer. We analyzed plasma samples from 39 patients with advanced or recurrent ovarian cancer enrolled in clinical trials for personalized peptide vaccinations. We observed that (1) the cfDNA integrity was decreased after the first cycle of vaccination, and (2) the decreased levels of cfDNA integrity were correlated with vaccine-induced immune responses; i.e., decreased cfDNA integrity was observed in 91.7% and 59.3% of the IgG-positive and negative patients, respectively (p = 0.0445). Similarly, decreased cfDNA integrity was observed in 92.9% and 56.0% of CTL response-positive and negative patients, respectively (p = 0.0283). These results suggest that the circulating cfDNA integrity is a possible biomarker for cancer vaccine therapy.
Highlights
Ovarian cancer is the eighth most common cancer in women, and each year worldwide, nearly 300,000 women newly develop ovarian cancer and 185,000 individuals die from it [1]
The total cell-free DNA (cfDNA) (Alu-115: the short 115-bp polymerase chain reaction (PCR) fragment of Alu) and the tumor cell-derived cfDNA (Alu-247: the long 247-bp PCR fragment of Alu) of each sample were quantified by real-time PCR, and the cfDNA integrity was calculated
Significant alterations in Alu-115 and Alu-247 were not observed during the first cycle of vaccination, whereas the cfDNA integrity was decreased during the vaccination, and the alteration was inversely and significantly correlated with the pre-vaccination levels of the cfDNA integrity (r = − 0.7974, p < 0.0001)
Summary
Ovarian cancer is the eighth most common cancer in women, and each year worldwide, nearly 300,000 women newly develop ovarian cancer and 185,000 individuals die from it [1]. The cancer vaccine consisted of 31 CTLepitope peptides, and a maximum of four peptides was selected from among the 31 peptides based on each patient’s HLA-A locus types and pre-vaccination immunity to the peptides; we refer to it as the "personalized peptide vaccination". Promising results such as the improvement of overall survival in the vaccine-treated group were obtained, only a limited number of patients received a clinical benefit from the vaccine [6,7,8,9,10,11]. The development of biomarkers that can be used to identify the patients who will benefit from the personalized peptide vaccination is an urgent and important issue
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