In the hands of surgeons experienced in robotic assisted laparoscopic radical prostatectomy and radical retropubic prostatectomy, there was a statistically significant lower positive margin rate for patients undergoing robotic assisted laparoscopic radical prostatectomy. The most common location of a positive surgical margin in robotic assisted laparoscopic radical prostatectomy and radical retropubic prostatectomy cases was at the apex. Patients treated with radical retropubic prostatectomy had higher risk features which may have independently influenced these results. The method of pathological specimen analysis and reporting may account for the higher positive margin rates in both groups compared to some reports.
The use of chimeric antigen receptor (CAR)-modified T cells as a therapy for hematologic malignancies and solid tumors is becoming more widespread. However, the infusion of a T-cell product targeting a single tumor-associated antigen may lead to target antigen modulation under this selective pressure, with subsequent tumor immune escape. With the purpose of preventing this phenomenon, we have studied the impact of simultaneously targeting two distinct antigens present on tumor cells: namely mucin 1 and prostate stem cell antigen, both of which are expressed in a variety of solid tumors, including pancreatic and prostate cancer. When used individually, CAR T cells directed against either tumor antigen were able to kill target-expressing cancer cells, but tumor heterogeneity led to immune escape. As a combination therapy, we demonstrate superior antitumor effects using both CARs simultaneously, but this was nevertheless insufficient to achieve a complete response. To understand the mechanism of escape, we studied the kinetics of T-cell killing and found that the magnitude of tumor destruction depended not only on the presence of target antigens but also on the intensity of expression-a feature that could be altered by administering epigenetic modulators that upregulated target expression and enhanced CAR T-cell potency.
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