Background: The clinical impact of severe coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in immunocompromised patients has not been systematically evaluated. Methods: We reviewed current literature reporting on COVID-19 in cancer (CA), hematopoietic cell (HCT), and solid organ transplant (SOT) patients and compared their clinical data and outcomes to the general population. For adult CA, HCT and SOT patients, an extensive search strategy retrieved all articles published until July 20, 2020 by combining the terms coronavirus, coronavirus infection, COVID-19 , and SARS-CoV-2 in PubMed, Cochrane, and Web of Science, and following the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. For the pediatric CA cohort, a global COVID-19 registry was used. For the general population cohort, a large meta-analysis was used to compare pooled prevalence estimates, and two large meta-analyses were utilized to serve as pooled comparators for hospitalized COVID-19 patients. Findings: Compared to the general population, adult CA and SOT patients with COVID-19 had higher comorbidities, greater levels of inflammatory markers at diagnosis, and higher rates of intensive care and hospital mortality. Pediatric CA patients and HCT patients with COVID-19 tended to have clinical presentations and outcomes similar to the general population. Interpretation: To our knowledge, this is the first systematic review evaluating COVID-19 phenotype and outcomes in immunocompromised patients and comparing them to the general population, which shows that hospital outcomes appear to be worse in adult CA and SOT patients, potentially due to their higher co-morbidity burden.

CRISPR/Cas9 technology is accelerating genome engineering in many cell types, but so far, gene delivery and stable gene modification have been challenging in primary NK cells. For example, transgene delivery using lentiviral or retroviral transduction resulted in a limited yield of genetically-engineered NK cells due to substantial procedure-associated NK cell apoptosis. We describe here a DNA-free method for genome editing of human primary and expanded NK cells using Cas9 ribonucleoprotein complexes (Cas9/RNPs). This method allowed efficient knockout of the TGFBR2 and HPRT1 genes in NK cells. RT-PCR data showed a significant decrease in gene expression level, and a cytotoxicity assay of a representative cell product suggested that the RNP-modified NK cells became less sensitive to TGFβ. Genetically modified cells could be expanded post-electroporation by stimulation with irradiated mbIL21-expressing feeder cells.

The adoptive transfer of natural killer (NK) cells is an emerging therapy in the field of immuno-oncology. In the last 3 decades, NK cells have been utilized to harness the anti-tumor immune response in a wide range of malignancies, most notably with early evidence of efficacy in hematologic malignancies. NK cells are dysfunctional in patients with hematologic malignancies, and their number and function are further impaired by chemotherapy, radiation, and immunosuppressants used in initial therapy and hematopoietic stem cell transplantation. Restoring this innate immune deficit may lead to improved therapeutic outcomes. NK cell adoptive transfer has proven to be a safe in these settings, even in the setting of HLA mismatch, and a deeper understanding of NK cell biology and optimized expansion techniques have improved scalability and therapeutic efficacy. Here, we review the use of NK cell therapy in hematologic malignancies and discuss strategies to further improve the efficacy of NK cells against these diseases.

Wilms tumor (WT) is the most prevalent pediatric renal tumor and most commonly occurs between ages 1 and 5 years. Data are lacking on children younger than 12 months with renal tumors. The cancer registry at the authors' institution was queried to identify patients 12 months and younger with renal masses. Demographics, clinical presentation, histopathology, stage, and survival outcomes were reviewed. The most common presenting symptoms included an asymptomatic abdominal mass (73%) and hematuria (9%). Histopathology revealed WT in 73% of patients, mesoblastic nephroma in 20%. Of those infants younger than 1 month of age, mesoblastic nephroma was the most common histopathology (68%). The 5-year overall survival (OS) was 93%, and 5-year event-free survival (EFS) was 93% for the entire group. For patients with WT, 5-year OS was 88% and 5-year EFS was 83%. Outcomes for congenital mesoblastic nephroma were excellent with 5-year OS and EFS of 100%. Reasons for good prognosis may be multifactorial and may include frequent well child checks in the first year of life and favorable histology. Patients in this age group are more likely to be classified as very low risk and may be treated with surgical resection alone.