Since its first approval by the FDA in 2017, tremendous progress has been made in chimeric antigen receptor (CAR) T cell therapy, the adoptive transfer of engineered, CAR-expressing T lymphocyte. CAR T cells are all composed of three main elements: an extracellular antigen-binding domain, an intracellular signaling domain responsible for T cell activation, and a hinge that joins these two domains. Continuous improvement has been made in CARs, now in their fifth generation, particularly in the intracellular signaling domain responsible for T cell activation. CAR T cell therapy has revolutionized the treatment of hematologic malignancies. Nonetheless, the use of CAR T cell therapy for solid tumors has not attained comparable levels of success. Here we review the challenges in achieving effective CAR T cell therapy in solid tumors, and emerging CAR T cells that have shown great promise for non-small cell lung cancer (NSCLC). A growing number of clinical trials have been conducted to study the effect of CAR T cell therapy on NSCLC, targeting different types of surface antigens. They include epidermal growth factor receptor (EGFR), mesothelin (MSLN), prostate stem cell antigen (PSCA), and mucin 1 (MUC1). Potential new targets such as erythropoietin-producing hepatocellular carcinoma A2 (EphA2), tissue factor (TF), and protein tyrosine kinase 7 (PTK7) are currently under investigation in clinical trials. The challenges in developing CAR T for NSCLC therapy and other approaches for enhancing CAR T efficacy are discussed. Finally, we provide our perspective on imaging CAR T cell action by reviewing the two main radionuclide-based CAR T cell imaging techniques, the direct labeling of CAR T cells or indirect labeling via a reporter gene.
1 February 2022 in Urologic Oncology: Seminars and Original Investigations
LigaSure® Small Jaw (LSJ) has been recently introduced as an energy-based vessel sealing device, which has provided better intraoperative and postoperative outcomes in thyroidectomies, compared to conventional technique. In the current study, we aimed to examine the efficiency of hand-sewn and LSJ thyroidectomy, based on operation time and perioperative complications. All patients with the diagnosis of multinodular goiter, thyroid cancers, retrosternal goiter and other indications for thyroid surgeries, enrolled. Of 550 patients, 261 patients randomly assigned to the conventional group (A) and 274 patients to LigaSure Small Jaw group (B). Study groups compared concerning operative time, recurrent laryngeal nerve (RLN) injury, hypocalcemia, and postoperative complications. There was no significant difference regarding demographic data between groups A and B. During total thyroidectomy, intraoperative blood loss was 64.42 ± 20.72 ml and 49.64 ± 17.92 ml in groups A and B, respectively (P 0.043). Operative time was significantly lower in LSJ group compared to the conventional group in total and subtotal thyroidectomy (P 0.002; P 0.001). Three patients who underwent conventional total thyroidectomy had RLN palsy. However, there was no significant difference between techniques regarding RLN injury (P 0.134). Postoperative total and ionized serum calcium levels decreased compared to preoperative levels in both conventional and LSJ technique; however, changes in total and ionized serum calcium were more severe in patients with conventional thyroidectomy (total calcium, P < 0.0001) (ionized calcium, P 0.005). The LigaSure Small Jaw device decreases operative time and intraoperative bleeding compared to conventional technique. Besides, changes in total and ionized calcium levels in patients with LSJ thyroidectomy are subtle compared to HS technique. Registered in Iranian Registry of Clinical Trials ( www.irct.com ), trial registration: IRCT2014010516077N1, Registered: 23 May 2014).
Objective: Stroke is a major cause of mortality and disability worldwide. People with stroke have a number of options available to treat post-stroke related symptoms and challenges. The aim of this study was to assess the use of healthcare services, self-care practices and out-of-pocket expenses associated with post-stroke healthcare. Methods: We retrospectively analysed data collected between April and October 2017 from a survey of 576 participants aged 55 to 96 from the 45 and Up Study, NSW (Australia), who had earlier reported a clinical diagnosis of stroke. Participants were asked about their use of health care services, including conventional medicine practitioners and medications, complementary medicine practitioners, practices and products and the respective associated out-of-pocket expenditure for each. Results: Amongst the total of 576 individuals who participated in the study, 39% consulted a doctor, 18% consulted an allied health practitioner, and 8% consulted a complementary medicine practitioner in the previous year for their stroke. Participants’ average combined out-of-pocket expenditure for post-stroke related healthcare was AU$386.4 per annum. Extrapolated to all Australians with stroke, aged 55 years and over, the total out-of-pocket expenditure for post-stroke related healthcare is estimated to be AU$42 million per annum. Conclusions: Post-stroke individuals used a wide range of health services and various self-care practices for stroke rehabilitation. Such healthcare utilisation is associated with significant annual out-of-pocket expenditure. Given the socioeconomic burden of stroke, further research is required to identify the barriers and facilitators of self-care among patients with stroke and explore the cost-effectiveness of the wide range of treatments(s) utilised for post-stroke care.