Novelty in improvement of CAR T cell-based immunotherapy with the aid of CRISPR system

Abstract Introduction Chimeric Antigen Receptor (CAR) T cells have tremendous potentials for cancer treatment; however, various challenges impede their universal use. These restrictions include the poor function of T cells in tumor microenvironments, the shortage of tumor-specific antigens and, finally, the high cost and time-consuming process, as well as the poor scalability of the method. Creative gene-editing tools have addressed each of these limitations and introduced next generation products for cell therapy. The clustered regularly interspaced short palindromic repeats-associated endonuclease 9 (CRISPR/Cas9) system has triggered a revolution in biology fields, as it has a great capacity for genetic manipulation. Method In this review, we considered the latest development of CRISPR/Cas9 methods for the chimeric antigen receptor T cell (CAR T)-based immunotherapy. Results The ability of the CRISPR/Cas9 system to generate the universal CAR T cells and also potent T cells that are persistent against exhaustion and inhibition was explored. Conclusion: We explained CRISPR delivery methods, as well as addressing safety concerns related to the use of the CRISPR/Cas9 system and their potential solutions.

Novelty in improvement of CAR T cell-based immunotherapy with the aid of CRISPR system.

INTRODUCTION: Chimeric Antigen Receptor (CAR) T cells have tremendous potentials for cancer treatment; however, various challenges impede their universal use. These restrictions include the poor function of T cells in tumor microenvironments, the shortage of tumor-specific antigens and, finally, the high cost and time-consuming process, as well as the poor scalability of the method. Creative gene-editing tools have addressed each of these limitations and introduced next generation products for cell therapy. The clustered regularly interspaced short palindromic repeats-associated endonuclease 9 (CRISPR/Cas9) system has triggered a revolution in biology fields, as it has a great capacity for genetic manipulation. METHOD: In this review, we considered the latest development of CRISPR/Cas9 methods for the chimeric antigen receptor T cell (CAR T)-based immunotherapy. RESULTS: The ability of the CRISPR/Cas9 system to generate the universal CAR T cells and also potent T cells that are persistent against exhaustion and inhibition was explored. CONCLUSION: We explained CRISPR delivery methods, as well as addressing safety concerns related to the use of the CRISPR/Cas9 system and their potential solutions.

Highlighting the interaction between immunomodulatory properties of mesenchymal stem cells and signaling pathways contribute to Graft Versus Host Disease management.

Background Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) has been increasingly used as a therapeutic approach for hematological malignancies. Several potential strategies have been developed for treating or preventing allo-HSCT complications, specifically graft-versus-host disease (GVHD). GVHD could significantly affect the morbidity and mortality of patients after allo-HSCT. Curative treatment and prophylaxis regimens for GVHD could reduce GVHD incidence and improve survival rate. Among these therapeutic strategies, mesenchymal stem cell (MSCs) mediated immunomodulation has been explored widely in clinical trials. MSCs immunomodulation ability in GVHD correlates with the interactions of MSCs with innate and adaptive immune cells. However, signaling pathways responsible for MSCs' impact on GVHD regulation, like JAK/STAT, NOTCH, MAPK/ERK, and NFκß signaling pathways, have not been clearly described yet. This review aims to illuminate the effect of MSCs-mediated immunomodulation in GVHD management after allo-HSCT representing the role of MSCs therapy on signaling pathways in GVHD. Conclusion MSCs could potentially modulate immune responses, prevent GVHD, and improve survival after allo-HSCT. Previous studies have investigated different signaling pathways' contributions to MSCs immunoregulatory ability. Accordingly, targeting signaling pathways components involved in MSCs related GVHD regulation is proven to be beneficial.

Plasma exchange followed by convalescent plasma transfusion in COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerged pandemic disease with no specific treatment. One of the potential treatments in newly found infectious disease is plasma exchange (PE) with convalescent plasma transfusion (CPT). This case series aimed to evaluate the primary PE and CPT in five Iranian COVID-19 patients. METHODS: Five patients with confirmed COVID-19 who had acute respiratory distress syndrome and were supported by mechanical ventilation were treated with two consecutive PE containing fresh frozen plasma (FFP) of healthy donors and 0.9 % saline solution containing 5 % human albumin. Thereafter, CPT was performed just like PE, except that the FFP in this step was substituted with convalescent ABO-matched plasma. Clinical and laboratory factors were evaluated before and after treatments. RESULTS: Three to Four patients showed lower body temperature and improved oxygen saturation as well as reduced laboratory factors such as c-reactive protein, lactate dehydrogenase, creatine phosphokinase (total and myocardial isoform), aspartate aminotransferase, blood urea nitrogen, bilirubin (total and direct), D-dimer, interleukin-6, and CD4+/CD8 + T cells ratio initially after PE and continued to improve so that they were discharged. One patient due to secondary hemophagocytic lymphohistiocytosis and extensive lung fungal infection was expired. DISCUSSION: Overall, the PE followed by CPT was beneficial in reducing acute inflammation led to a considerable improvement in patients' clinical features. It seems that PE along with CPT could provide clearance of pro-inflammatory mediators as well as the positive effects of CPT. Controlled studies are required to confirm the effect of PE/CPT compared with other therapeutic approaches.

An uncommon presentation of hepatic hydatid cyst leading to biliary cirrhosis and portal hypertension.

Hydatid disease is an ongoing issue in endemic areas. Hydatid cysts can be seen in any organ but, liver is one of the most common involved organs. Cystobiliary communication as an overwhelming complication of hepatic hydatid cysts can contribute to the obstructive jaundice, cholangitis, sepsis and even biliary cirrhosis if left untreated. The patient we are trying to present is a 61-year-old farmer who presented with obstructive jaundice, multiple common bile duct stones and biliary cirrhosis attributed to a long-lasting untreated hepatic hydatid cyst. Portal hypertension is introduced to be an uncommon presentation of hydatid cyst. Extrinsic compression of the porta hepatis and obstruction of inferior vena cava are amongst major causes of hydatidosis leading up to portal hypertension as reported in the literature. Portal hypertension in the presented case is proposed to emerge from long-lasting cystobiliary communication ending in biliary cirrhosis.

Video Laryngoscopy or Macintosh Laryngoscopy: Which One Is More Successful in Patients With Bilateral Mandibular Fractures?

PURPOSE: Successful intubation is challenging in patients with bilateral mandibular fractures. The aim of this study was to compare the video laryngoscope (VL) with the Macintosh laryngoscope (ML) for intubation of patients with bilateral mandibular fractures. MATERIALS AND METHODS: In this randomized controlled trial study, patients who had bilateral mandibular fractures (angle or subcondylar) were studied. Patients were randomly assigned to 1 of 2 groups using computerized randomization. Laryngoscopy was performed by the ML in group 1 and the VL in group 2. Intubation device (ML or VL) was the predictive factor of the study and age, maximum mouth opening (MMO), incisor fracture, and gender were the variables. Intubation time and successful intubation at the first attempt were the study outcomes. Independent t test was applied to compare intubation time, MMO, and age between the 2 groups. RESULTS: Seventy-eight patients were studied (40 in group 1 and 38 in group 2). Mean intubation time was 33.02 ± 9.68 seconds in group 1 and 39.16 ± 7.40 seconds in group 2. Comparison of the data showed a significant difference between the 2 groups (P = .002). Twenty-four patients in group 1 and 31 in group 2 were successfully intubated at the first attempt. There was a significant difference in the number of successful or failed intubation attempts between the 2 groups (P = .03). CONCLUSION: According to the present findings, use of the VL increased the first-attempt success rate of intubation in patients with bilateral mandibular fractures. Time of intubation could be longer when using the VL than when using the ML.