Noah Richardson

B cells and reduced disease in naive autoimmune mice, indicating that disease control was cell-mediated. Sustained B cell depletion with CD19-targeted CAR T cell immunotherapy is a stable and effective strategy to treat murine lupus, and its effectiveness should be explored in clinical trials for lupus.

BACKGROUND: Simultaneous advances in gene editing, T cell engineering and biotechnology currently provide an opportunity for rapid progress in medicine. The approval of chimeric antigen receptor (CAR) T cell therapies by the US Food and Drug Administration (FDA) and the European Commission have generated substantial momentum for these first-in-class therapies to be used in patients with B cell malignancies. MAIN BODY: Considerable efforts focus on improved outcomes and reduced side effects of the newly approved therapies. Using innovative strategies, researchers aim to extend CAR T cell use to tackle difficulties inherent in solid tumors. Efforts are underway to broaden the applications of CAR T cells, and the strategy has been successful in chronic viral infections and preclinical models of autoimmunity. Research is in progress to generate "off-the-shelf" CAR T cells, an advance, which would greatly increase patient availability and reduce treatment cost. CONCLUSIONS: In this thematic review, we highlight advances that may help develop genetically engineered cells into a new category of medical therapies.

Abstract Background Patients with relapsed primary mediastinal nonseminomatous germ cell tumor have low cure rates with salvage chemotherapy or surgery. The authors report survival outcomes of patients who received high‐dose chemotherapy (HDCT) and peripheral blood stem cell transplantation (PBSCT) at Indiana University. Methods The prospectively maintained Indiana University germ cell tumor database identified 32 patients with primary mediastinal nonseminomatous germ cell tumor who progressed after first‐line cisplatin‐based combination chemotherapy and received HDCT and PBSCT between 2006 and 2021. Therapy included two consecutive courses of HDCT consisting of 700 mg/m 2 carboplatin and 750 mg/m 2 etoposide, each for 3 consecutive days, and each followed by PBSCT. A second course was not given if the patient experienced progressive disease or prohibitive toxicity. Progression‐free survival and overall survival were analyzed using the Kaplan–Meier method. Medians with 95% confidence intervals were also calculated along with 2‐year probabilities. Results The median age at HDCT was 30 years (range, 18–61 years). With a median follow‐up of 4.7 years (range, 1–14 years), the 2‐year progression‐free survival rate was 31% (95% confidence interval, 16%–47%), and the 2‐year overall survival rate was 35% (95% confidence interval, 19%–52%). At last follow‐up, nine patients (28%) remained without evidence of disease, including two platinum‐refractory patients and two patients who were receiving HDCT as third‐line therapy. There were three treatment‐related deaths. Conclusions Salvage HDCT and PBSCT is an active combination in patients who have relapsed primary mediastinal nonseminomatous germ cell tumor with curative potential and prolonged survival, including in platinum‐refractory and third‐line settings. The authors recommend this approach for initial salvage chemotherapy in this patient population.