Chimeric antigen receptor (CAR)-T cell therapy is a promising form of immunotherapy that has seen significant advancements in the past few decades. It involves genetically modifying T cells to target cancer cells expressing specific antigens, providing a novel approach to treating various types of cancer. However, the initial success of first-generation CAR-T cells was limited due to inadequate proliferation and undesirable outcomes. Nonetheless, significant progress has been made in CAR-T cell engineering, leading to the development of the latest fifth-generation CAR-T cells that can target multiple antigens and overcome individual limitations. Despite these advancements, some shortcomings prevent the widespread use of CAR-T therapy, including life-threatening toxicities, T-cell exhaustion, and inadequate infiltration for solid tumors. Researchers have made considerable efforts to address these issues by developing new strategies for improving CAR-T cell function and reducing toxicities. This review provides an overview of the path of CAR-T cell development and highlights some of the prominent advances in its structure and manufacturing process, which include the strategies to improve antigen recognition, enhance T-cell activation and persistence, and overcome immune escape. Finally, the review briefly covers other immune cells for cancer therapy and ends with the discussion on the broad prospects of CAR-T in the treatment of various diseases, not just hematological tumors, and the challenges that need to be addressed for the widespread clinical application of CAR-T cell therapies.
15 February 2024 in British Journal of Haematology
Unicentric Castleman disease (UCD) is a rare lymphoproliferative disorder presenting as a single nodal mass with characteristic histopathology. Patients with UCD are typically asymptomatic with normal laboratory markers, whereas patients with multicentric Castleman disease (MCD) demonstrate multicentric lymphadenopathy and cytokine storm–induced systemic inflammatory symptoms. This retrospective analysis of 116 UCD cases identified 19 (16.4%) cases with an MCD-like inflammatory state (UCD-MIS). We compared treatments and outcomes between cases of UCD-MIS and UCD–non-MIS to evaluate the role of surgery and illuminate biological behavior of UCD-MIS. There were differences in the distribution of histopathological subtypes (plasmacytic histopathology was more frequently seen, 52.6% vs 13.4%; P < .001) between the 2 groups. However, both groups demonstrated good responses to surgical treatment, suggesting that UCD-MIS in some patients still shared common biological behavior with UCD in other patients. Sixteen (94.2%) patients with UCD-MIS underwent complete surgical excision alone, and the systemic inflammation resolved completely in all of them. This high response rate suggests surgical treatment as a potential cure for this unique subset of patients. After a median follow-up duration of 64 months (range, 2-239 months), neither lymphadenopathy nor the inflammatory state recurred. However, inflammation may progress in patients with irresectable disease, and treatment options other than surgery should be considered in these patients.
1 August 2021 in Journal of Diabetes and its Complications
This study aims to construct a logistically derived additive score for predicting in-hospital mortality risk in Chinese patients undergoing coronary artery bypass surgery (CABG). Data from 9839 consecutive CABG patients in 43 Chinese centers were collected between 2007 and 2008 from the Chinese Coronary Artery Bypass Grafting Registry. This database was randomly divided into developmental and validation subsets (9:1). The data in the developmental dataset were used to develop the model using logistic regression. Calibration and discrimination characteristics were assessed using the validation dataset. Thresholds were defined for each model to distinguish different risk groups. After excluding 275 patients with incomplete information, the overall mortality rate of the remaining 9564 patients was 2.5%. The SinoSCORE model was constructed based on 11 variables: age, preoperative NYHA stage III or IV, chronic renal failure, extracardiac arteriopathy, chronic obstructive pulmonary disease, preoperative atrial fibrillation or flutter (within 2 weeks), left ventricular ejection fraction, other elective surgery, combined valve procedures, preoperative critical state, and BMI. In the developmental dataset, calibration using a Hosmer-Lemeshow (HL) test was at P = 0.44 and discrimination based on the area under the receiver operating characteristic curve (ROC) was 0.80. In the validation dataset, the HL test was at P = 0.34 and the area under the ROC (AUC) was 0.78. A logistically derived additive model for predicting in-hospital mortality among Chinese patients undergoing CABG was developed based on the most up-to-date multi-center data from China.