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BackgroundIn colorectal cancer, the effects of immune checkpoint inhibitors are mostly limited to patients with deficient mismatch repair tumors, characterized by a high grade infiltration of CD8+T cells. Interventions aimed at increasing intratumoral CD8+T-cell infiltration in proficient mismatch repair tumors are lacking.MethodsWe conducted a proof of concept phase 1/2 clinical trial, where patients with non-metastasizing sigmoid or rectal cancer, scheduled for curative intended surgery, were treated with an endoscopic intratumorally administered neoadjuvant influenza vaccine. Blood and tumor samples were collected before the injection and at the time of surgery. The primary outcome was safety of the intervention. Evaluation of pathological tumor regression grade, immunohistochemistry, flow cytometry of blood, tissue bulk transcriptional analyses, and spatial protein profiling of tumor regions were all secondary outcomes.ResultsA total of 10 patients were included in the trial. Median patient age was 70 years (range 54–78), with 30% women. All patients had proficient mismatch repair Union of International Cancer Control stage I–III tumors. No endoscopic safety events occurred, with all patients undergoing curative surgery as scheduled (median 9 days after intervention). Increased CD8+T-cell tumor infiltration was evident after vaccination (median 73 vs 315 cells/mm2, pConclusionsNeoadjuvant intratumoral influenza vaccine treatment in this cohort was demonstrated to be safe and feasible, and to induce CD8+T-cell infiltration and upregulation of PD-L1 proficient mismatch repair sigmoid and rectal tumors. Definitive conclusions regarding safety and efficacy can only be made in larger cohorts.Trial registration numberNCT04591379.

One of the most focused-on point in biomedical and biotechnological research is the fabrication of complex tissue engineering scaffolds, with the ultimate objective being a functional, biocompatible and biodegradable implant that could facilitate and enhance tissue regeneration. Creating such implants is a highly challenging task. Physical and chemical characteristics have to be optimized and the balance between biodegradability, mechanical strength and overall practicality cannot be easily obtained. In this regard, composite materials have been regularly used in numerous areas of science and engineering as they incorporate advantages from two or more component materials. Our objective was to fabricate a composite, fibrous mesh composed of both degradable and non-degradable elements, that could be applicable as an implant with reliable mechanical properties without hindering in vivo tissue integration. In the manuscript, we present the fabrication, chemical, physical, mechanical and cytotoxic evaluation of co-electrospun polysuccinimide/poly(vinyl alcohol) (PSI/PVA) meshes. Results confirmed the presence and random distribution of both PSI and PVA fibres in the fabricated meshes. Mechanical studies indicate that meshes are competent for implantation while cell viability study revealed no cytotoxic effects.