Solitary meningeal recurrence in a patient with transitional cell carcinoma of the bladder with locally bulky disease at presentation

Patients with locally advanced transitional cell carcinoma (TCC)of the bladder are at high risk forsystemic relapse, with liver, bone and lung beingthe commonest sites of metastases.We report the case of a 52-year-old womanwith a solitary meningeal relapse, a rare siteof recurrence, after 8 months of complete remissionobtained with M-VEC for locally advanced TCC ofthe bladder. We speculate on the likely riskfactors related to this unusual site of recurrence.     

Chimeric antigen receptor-modified human regulatory T cells that constitutively express IL-10 maintain their phenotype and are potently suppressive

Clinical trials of Treg therapy in transplantation are currently entering phases IIa and IIb, with the majority of these employing polyclonal Treg populations that harbor a broad specificity. Enhancing Treg specificity is possible with the use of chimeric antigen receptors (CARs), which can be customized to respond to a specific human leukocyte antigen (HLA). In this study, we build on our previous work in the development of HLA-A2 CAR-Tregs by further equipping cells with the constitutive expression of interleukin 10 (IL-10) and an imaging reporter as additional payloads. Cells were engineered to express combinations of these domains and assessed for phenotype and function. Cells expressing the full construct maintained a stable phenotype after transduction, were specifically activated by HLA-A2, and suppressed alloresponses potently. The addition of IL-10 provided an additional advantage to suppressive capacity. This study therefore provides an important proof-of-principle for this cell engineering approach for next-generation Treg therapy in transplantation.