Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is lethal in 88% of patients1, yet harbours mutation-derived T cell neoantigens that are suitable for vaccines 2,3. Here in a phase I trial of adjuvant autogene cevumeran, an individualized neoantigen vaccine based on uridine mRNA-lipoplex nanoparticles, we synthesized mRNA neoantigen vaccines in real time from surgically resected PDAC tumours. After surgery, we sequentially administered atezolizumab (an anti-PD-L1 immunotherapy), autogene cevumeran (a maximum of 20 neoantigens per patient) and a modified version of a four-drug chemotherapy regimen (mFOLFIRINOX, comprising folinic acid, fluorouracil, irinotecan and oxaliplatin). The end points included vaccine-induced neoantigen-specific T cells by high-threshold assays, 18-month recurrence-free survival and oncologic feasibility. We treated 16 patients with atezolizumab and autogene cevumeran, then 15 patients with mFOLFIRINOX. Autogene cevumeran was administered within 3 days of benchmarked times, was tolerable and induced de novo high-magnitude neoantigen-specific T cells in 8 out of 16 patients, with half targeting more than one vaccine neoantigen. Using a new mathematical strategy to track T cell clones (CloneTrack) and functional assays, we found that vaccine-expanded T cells comprised up to 10% of all blood T cells, re-expanded with a vaccine booster and included long-lived polyfunctional neoantigen-specific effector CD8+ T cells. At 18-month median follow-up, patients with vaccine-expanded T cells (responders) had a longer median recurrence-free survival (not reached) compared with patients without vaccine-expanded T cells (non-responders; 13.4 months, P = 0.003). Differences in the immune fitness of the patients did not confound this correlation, as responders and non-responders mounted equivalent immunity to a concurrent unrelated mRNA vaccine against SARS-CoV-2. Thus, adjuvant atezolizumab, autogene cevumeran and mFOLFIRINOX induces substantial T cell activity that may correlate with delayed PDAC recurrence.

Enhanced PAtient Clinical Streamlining (EPACS): Quality Initiative to Improve Healthcare for New Surgical Outpatient Visits.

PURPOSE: For patients who select a specialty hospital for cancer treatment, the wait time until the initial consultation leaves patients anxious and delays treatment. To improve quality of care, we implemented an enhanced patient clinical streamlining (EPACS) process that establishes an early connection and coordinates care before the first surgical outpatient visit at our specialty cancer center. METHODS: During a pre-visit EPACS phone call to new patients, an advanced practice provider (APP) collected medical history and ordered work-up tests or consultations if feasible. First visit cancellation rate, number of patients who started treatment, time to start of treatment, and satisfaction by the care team and patient were compared between patients treated with versus without EPACS. RESULTS: Among 5062 consecutive new patients, 720 (14%) received an EPACS call and 4342 did not (86%); work-up was ordered pre-visit in 34% and 16%, respectively. Fewer EPACS patients cancelled the first visit (4.6% vs. 12%, p < 0.001), more started treatment (55% vs. 50%, p = 0.037), and their time to treatment was shorter, but not significantly (median 17 vs. 19 days, p = 0.086). Patient interaction was considered to be improved by EPACS by 17 of 17 APPs and 14 of 16 surgeons, and outpatient clinic efficiency by 14 of 17 APPs and 13 of 16 surgeons. EPACS reduced anxiety and increased preparedness for the first visit in 29 of 31 patients. CONCLUSIONS: EPACS improved effectiveness, timeliness, and physician and patient satisfaction with health care at our cancer center.