Autologous dendritic cells pulsed with allogeneic tumour cell lysate induce tumour-reactive T-cell responses in patients with pancreatic cancer: A phase I study.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is notorious for its poor prognosis even after curative resection. Responses to immunotherapy are rare and related to inadequate T-cell priming. We previously demonstrated the potency of allogeneic lysate-dendritic cell (DC) vaccination in a preclinical model. Here we translate this concept to patients. METHODS: In this phase I study, patients with resected PDAC were included when they demonstrated no radiologic signs of recurrence after standard-of-care treatment. Allogeneic tumour lysate-loaded autologous monocyte-derived DCs were injected at weeks 0, 2, 4 and at months 3 and 6. Objectives are feasibility, safety and immunogenicity of allogeneic tumour-DCs. The presence of tumour antigens shared between the vaccine and patient tumours was investigated. Immunological analyses were performed on peripheral blood, skin and tumour. RESULTS: Ten patients were included. DC production and administration were successful. All patients experienced a grade 1 injection-site and infusion-related reaction. Two patients experienced a grade 2 fever and 1 patient experienced a grade 3 dyspnoea. No vaccine-related serious adverse events were observed. Shared tumour antigens were found between the vaccine and patient tumours. All evaluated patients displayed a vaccine-induced response indicated by increased frequencies of Ki67+ and activated PD-1+ circulating T-cells. In addition, treatment-induced T-cell reactivity to autologous tumour of study patients was detected. Seven out of ten patients have not experienced disease recurrence or progression at a median follow-up of 25 months (15-32 months). CONCLUSION: Allogeneic tumour lysate-DC treatment is feasible, safe and induces immune reactivity to PDAC expressed antigens.

Prevalence of chromosomal abnormalities and timing of karyotype analysis in patients with recurrent implantation failure (RIF) following assisted reproduction.

AIMS: To analyze the prevalence and type of karyotype abnormalities in RIF patients and to evaluate the adequate timing for analysis and the presence of possible risk factors. METHODS: 615 patients (317 women and 298 men) with RIF, having undergone at least 3 sequential failed IVF/ICSI cycles prior to karyotype analysis, were included in this study. Anomaly rates found were compared with published series. RESULTS: Chromosomal abnormalities were diagnosed in 2.1% of patients (13/615): 8 females (2.5%) and 5 males (1.7%) which is significantly higher for the females than in unselected newborns (0.8%) and normo-ovulatory women (0.6%) but lower than in women with high-order implantation failure (10.8%). No significant differences were found with couples at the start of IVF/ICSI (2.0%). Karyotyping all patients prior to IVF/ICSI results in a higher cost than selecting RIF patients. Two subgroups showed an increased prevalence of abnormalities: secondary infertile women with a history of only miscarriages (9.1%) and women with female infertility (6.0%). CONCLUSION: A karyotype analysis is indicated in all women with RIF. Nulliparous women with a history of mis-carriage and women with documented infertility are at greater risk of CA and are to be advised to undergo -karyotyping.