Evolving adoptive cellular therapies in urological malignancies

Abstract

Immunotherapies have long been used to treat urological cancers but rarely lead to cure. In the past 5 years, success of immune checkpoint inhibition has led to a resurgence of enthusiasm for immunotherapy in the treatment of solid tumours. Increased understanding of tumour immune biology, technological advancements of gene transfer and cell culture, and improved clinical infrastructures for routine delivery of cell products, has made cell-based immunotherapeutics a real prospect for cancer therapy. These scientific and clinical activities, attempting to exploit the innate and adaptive immune systems for therapeutic gain, are well exemplified by the urological malignancies of renal, bladder, prostate, and penile cancer, a group of anatomically localised diseases, each with a distinct biology and different immunotherapeutic challenges. In this Review, we present the results of clinical studies investigating autologous cellular therapies in urological malignancies. Specifically, we discuss the rationale for upcoming studies, and how novel therapies and adoptive cell combinations can be used for personalised cancer therapy.

Immunological Risk Stratification of Bladder Cancer Based on Peripheral Blood Natural Killer Cell Biomarkers

“…3A). Lower progression-free rates were observed for both HLA-C*16:01 (8.3%) and Genetic data from bladder cancer, OSC [23], and PCD [24] series coincides with a series used in previous studies aimed at describing the role of NK cell education in tumor immune surveillance. * HLA-I ligands for KIR2DS4 [21].…”

“…The aim of this study was to explore the role of NKcs in BC immunosurveillance by analyzing the association of KIR/ HLA-I interactions with BC diagnosis, tumor stage, and patient outcomes. We propose an immunological risk stratification model that complements histopathology to optimize personalized therapies [23].…”

Rapid expansion in the WAVE bioreactor of clinical scale cells for tumor immunotherapy

“…In addition, the semi-open system coupled with frequent culture manipulations introduces multiple opportunities for contamination, thus, highly skilled personnel are required. 34,35 These technical challenges have proved to be an impediment to a wider dissemination of cell-based immunotherapy. In order to rapidly expand on a large scale by simultaneously, keeping the most comfortable culture circumstances, our laboratory took advantage of the WAVE bioreactor for cultivation.…”

NK Cell-Based Immunotherapy in Renal Cell Carcinoma

“…Adoptive cell therapy has also been used for the treatment of metastatic RCC. Infusion of activated NK cells in combination with IL-2 [81,202,203], and the adoptive transfer of allogeneic NK cells [77] and NK cell lines, such as NK-92 [204], have been tested [142,205]. Infusions of NK cells have also been combined with other therapeutic procedures.…”