OncoTherad® (MRB-CFI-1) Nanoimmunotherapy: A Promising Strategy to Treat Bacillus Calmette-Guérin-Unresponsive Non-Muscle-Invasive Bladder Cancer: Crosstalk among T-Cell CX3CR1, Immune Checkpoints, and the Toll-Like Receptor 4 Signaling Pathway.

This study assessed the safety and efficacy of OncoTherad® (MRB-CFI-1) nanoimmunotherapy for non-muscle invasive bladder cancer (NMIBC) patients unresponsive to Bacillus Calmette-Guérin (BCG) and explored its mechanisms of action in a bladder cancer microenvironment. A single-arm phase I/II study was conducted with 44 patients with NMIBC who were unresponsive to BCG treatment. Primary outcomes were pathological complete response (pCR) and relapse-free survival (RFS). Secondary outcomes comprised response duration and therapy safety. Patients' mean age was 65 years; 59.1% of them were refractory, 31.8% relapsed, and 9.1% were intolerant to BCG. Moreover, the pCR rate after 24 months reached 72.7% (95% CI), whereas the mean RFS reached 21.4 months. Mean response duration in the pCR group was 14.3 months. No patient developed muscle-invasive or metastatic disease during treatment. Treatment-related adverse events occurred in 77.3% of patients, mostly grade 1-2 events. OncoTherad® activated the innate immune system through toll-like receptor 4, leading to increased interferon signaling. This activation played a crucial role in activating CX3CR1+ CD8 T cells, decreasing immune checkpoint molecules, and reversing immunosuppression in the bladder microenvironment. OncoTherad® has proved to be a safe and effective therapeutic option for patients with BCG-unresponsive NMIBC, besides showing likely advantages in tumor relapse prevention processes.

Evaluation of the tissue repair process and immunomodulatory action of Platelet-Rich Plasma (PRP) in the treatment of abdominal stretch marks.

The aims of this study were to characterize and to compare the structural alterations of collagen and elastic fibers in the abdominal stretch marks of patients submitted to intralesional and per quadrant (region close to stretch marks) Platelet-Rich Plasma (PRP) treatment, as well as, to establish the possible mechanisms of action of this treatment involving toll-like receptors (TLRs) signaling pathways and growth factors. Incisional biopsies were collected from abdominal stretch marks with a 2 mm diameter punch in female patients, at the beginning of treatment, after 6 and 12 weeks of treatment, and submitted to morphological analyzes of elastic and collagen fibers, and immunohistochemistry for TLRs signaling pathways and growth factors. Our results demonstrated PRP per quadrant treatment was most effective in reducing the area of the abdominal stretch marks, with consequent stimulation of the synthesis and remodeling of collagen and elastic fibers. Also, PRP per quadrant treatment promoted an increase in TLR2 and TLR4 immunoreactivities, with consequent increase in TNF-α, VEGF and IGF-1. Based on the current findings, PRP constitutes a promising therapeutic approach in patients with stretch marks, since it promoted modulation of inflammatory cytokines and growth factors, with consequent remodeling of extracellular matrix, culminating with tissue improvement.