ABSTRACT
Treatment options for ovarian cancer patients are limited, and a high unmet clinical need remains for targeted and long-lasting, efficient drugs. Genetically modified T cells expressing chimeric antigen receptors (CAR), are promising new drugs that can be directed towards a defined target and have shown efficient, as well as persisting, anti-tumor responses in many patients. We sought to develop novel CAR T cells targeting ovarian cancer and to assess these candidates preclinically. First, we identified potential CAR targets on ovarian cancer samples. We confirmed high and consistent expressions of the tumor-associated antigen FOLR1 on primary ovarian cancer samples. Subsequently, we designed a series of CAR T cell candidates against the identified target and demonstrated their functionality against ovarian cancer cell lines in vitro and in an in vivo xenograft model. Finally, we performed additional in vitro assays recapitulating immune suppressive mechanisms present in solid tumors and developed a process for the automated manufacturing of our CAR T cell candidate. These findings demonstrate the feasibility of anti-FOLR1 CAR T cells for ovarian cancer and potentially other FOLR1-expressing tumors.
ABSTRACT
As fistulas liquóricas rinogênicas são definidas como comunicações entre as fossas nasais e o espaço subaracnóideo. A origem dessas falhas pode ser de origem traumática ou não traumática, e o quadro clínico cursa com rinorréia ou otorréia citrina, geralmente unilateral. As fístulas não traumáticas espontâneas são menos comuns de ocorrer do que as traumáticas. O paciente relatado apresentava um quadro de rinoliquorreia através de fossa nasal direita, com aumento de fluxo ao se inclinar para frente e/ou realizar flexão anterior do pescoço. Realizando investigação diagnóstica por imagem a tomografia computadorizada de seios da face evidenciou a fístula localizada em recesso lateral de seio esfenoidal direito. Nesse caso o paciente foi submetido a correção cirúrgica, sendo escolhida uma abordagem endoscópica endonasal transpitrigoide para acessar a região do defeito. Realizado o fechamento da fístula o paciente evoluiu sem sinais de recidiva e sem outras sintomatologias.
Rhinogenic cerebrospinal fluid (CSF) leaks are communications between the nasal cavities and the subarachnoid space. The etiology of these leaks could be traumatic or non-traumatic, citrus rhinorrhea or otorrhea are the most common symptoms. The spontaneous non-traumatic leaks are less common to occur than the traumatic ones. The reported patient had CSF rhinorrhea through the right nostril, with an increased flow when leaning forward and/or perform anterior neck flexion. Imaging diagnostic by computed tomography cisternography showed the leak located in the lateral recess of the right sphenoid sinus. In this case the patient underwent a surgical procedure, the choice was an endoscopic endonasal traspterygoid approach to access the defect. A robust reconstruction of the defect was performed and the patient evolved without signs of recurrence or any other symptoms.
