Chimeric Antigen Receptor Structure and Manufacturing of Clinical Grade CAR Engineered Cells using Different Bioreactors.

Increasing success of adaptive cell therapy (ACT), such as genetically engineered T cells to express chimeric antigen receptors (CARs) proven to be highly significant technological advancements and impressive clinical outcomes in selected haematological malignancies, with promising efficacy. The evolution of CAR designs beyond the conventional structures is necessary to address some of the limitations of conventional CAR therapy and to expand the use of CAR T cells to a wider range of malignancies. There are various obstacles with a wide range of engineering strategies in order to improve the safety, efficacy and applicability of this therapeutic modality. Here we describe details of modular CAR structure with all the necessary domains and what is known about proximal CAR signalling in T cells. Furthermore, the global need for adoptive cell therapy is expanding very rapidly, and there is an urgent increasing demand for fully automated manufacturing methods that can produce large scale clinical grade high quality CAR engineered immune cells. Despite the advances in automation for the production of clinical grade CAR engineered cells, the manufacturing process is costly, consistent and involves multiple steps, including selection, activation, transduction, and Ex-Vivo expansion. Among these complex manufacturing phases, the choice of culture system to generate a high number of functional cells needs to be evaluated and optimized. Here we list the most advance fully automated to semi-automated bioreactor platforms can be used for the production of clinical grade CAR engineered cells for clinical trials but are far from being standardized. New processing options are available and a systematic effort seeking automation, standardization and the increase of production scale, would certainly help to bring the costs down and ultimately democratise this personalized therapy. In this review, we describe in detail different CAR engineered T cell platforms available and can be used in future for clinical-grade CAR engineered ATMP production.

Radiation Induced Multiple Skin Neoplasms Following Craniospinal Irradiation for Medulloblastoma. A Case Report.

BACKGROUND Following craniospinal irradiation in children with medulloblastoma, secondary neoplasms are among the most serious long-term sequelae that include leukemias and solid tumors of the urinary or digestive tracts, thyroid, skin, and central nervous system. Furthermore, in children with Gorlin syndrome following craniospinal irradiation for medulloblastoma, there is a rising incidence of skin and non-skin malignancies. CASE REPORT The patient in the present study was a 19-year-old female who was treated with craniospinal irradiation and chemotherapy following gross total resection (GTR) for medulloblastoma at the age of 4 years. Fifteen years later, she developed a primary adnexal tumor at the medial aspect of her left thigh, glomangioma at the skin of her upper abdomen, dermatofibrosarcoma protruberans at the skin of her upper back, and Kaposiform hemangioendothelioma of the upper abdomen. All these tumors were successfully managed with radical resection without further adjuvant treatment. CONCLUSIONS Metachronous of development of 4 histopathologically different skin tumors following craniospinal irradiation for medulloblastoma in long-term survivors has not previously been reported. The present case warrants a detailed dermatological periodic inspection in such patients.

Is the epidemiology of alkhurma hemorrhagic fever changing?: A three-year overview in Saudi Arabia.

BACKGROUND: The epidemiology of Alkhurma hemorrhagic fever disease is yet to be fully understood since the virus was isolated in 1994 in the Kingdom of Saudi Arabia. SETTING: Preventive Medicine department, Ministry of Health, Kingdom of Saudi Arabia. DESIGN: Retrospective analysis of all laboratory confirmed cases of Alkhurma hemorrhagic fever disease collected through active and passive surveillance from 1(st)-January 2009 to December, 31, 2011. RESULTS: Alkhurma hemorrhagic fever (AHFV) disease increased from 59 cases in 2009 to 93 cases in 2011. Cases are being discovered outside of the region where it was initially diagnosed in Saudi Arabia. About a third of cases had no direct contact with animals or its products. Almost all cases had gastro-intestinal symptoms. Case fatality rate was less than 1%. CONCLUSIONS: Findings in this study showed the mode of transmission of AHFV virus may not be limited to direct contact with animals or its products. Gastro-intestinal symptoms were not previously documented. Observed low case fatality rate contradicted earlier reports. Close monitoring of the epidemiology of AHFV is recommended to aid appropriate diagnosis. Housewives are advised to wear gloves when handling animals and animal products as a preventive measure.