From the Operating Room to Online: Medical Student Surgery Education in the Time of COVID-19.

BACKGROUND: On March 17, 2020 the Association of American Medical Colleges recommended dismissal of medical students from clinical settings due to the COVID-19 pandemic. Third-year (M3) and fourth-year (M4) medical students were at home, M4s were interested in teaching, and residents and faculty had fewer clinical responsibilities due to elective surgery cancellations. To continue M3 access to education, we created a virtual surgery elective (VSE) that aimed to broaden students' exposure to, and elicit interest in, general surgery (GS). METHODS: Faculty, surgical residents, and M4s collaborated to create a 2-wk VSE focusing on self-directed learning and direct interactions with surgery faculty. Each day was dedicated to a specific pathology commonly encountered in GS. A variety of teaching methods were employed including self-directed readings and videos, M4 peer lectures, case-based learning and operative video review with surgery faculty, and weekly surgical conferences. A VSE skills lab was also conducted to teach basic suturing and knot-tying. All lectures and skills labs were via Zoom videoconference (Zoom Video Communications Inc). A post-course anonymous survey sent to all participants assessed changes in their understanding of GS and their interest in GS and surgery overall. RESULTS: Fourteen M3s participated in this elective over two consecutive iterations. The survey response rate was 79%. Ninety-one percent of students believed the course met its learning objectives "well" or "very well." Prior to the course, 27% reported a "good understanding" and 0% a "very good" understanding of GS. Post-course, 100% reported a "good" or "very good" understanding of GS, a statistically significant increase (P = 0.0003). Eighty-two percent reported increased interest in GS and 64% reported an increase in pursuing GS as a career. CONCLUSIONS: As proof of concept, this online course successfully demonstrated virtual medical student education can increase student understanding of GS topics, increase interest in GS, and increase interest in careers in surgery. To broaden student exposure to GS, we plan to integrate archived portions of this course into the regular third-year surgery clerkship and these can also be used to introduce GS in the preclinical years.

Engineering Improved CAR T Cell Products with A Multi-Cytokine Particle Platform for Hematologic and Solid Tumors.

Despite the remarkable clinical efficacy of chimeric antigen receptor (CAR) T cells in hematological malignancies, only a subset of patients achieves a durable complete response (dCR). DCR has been correlated with CAR T cell products enriched with T cells memory phenotypes. Therefore, reagents that consistently promote memory phenotypes during the manufacturing of CAR T cells have the potential to significantly improve clinical outcomes. A novel modular multi-cytokine particle (MCP) platform is developed that combines the signals necessary for activation, costimulation, and cytokine support into a single "all-in-one" stimulation reagent for CAR T cell manufacturing. This platform allows for the assembly and screening of compositionally diverse MCP libraries to identify formulations tailored to promote specific phenotypes with a high degree of flexibility. The approach is leveraged to identify unique MCP formulations that manufacture CAR T cell products from diffuse large B cell patients   with increased proportions of memory-like phenotypes MCP-manufactured CAR T cells demonstrate superior anti-tumor efficacy in mouse models of lymphoma and ovarian cancer through enhanced persistence. These findings serve as a proof-of-principle of the powerful utility of the MCP platform to identify "all-in-one" stimulation reagents that can improve the effectiveness of cell therapy products through optimal manufacturing.

Using Adoptive Cellular Therapy for Localized Protein Secretion.

ABSTRACT: Redirection of T cell cytotoxicity by the chimeric antigen receptor (CAR) structure may not be sufficient for optimal antitumor function in the patient tumor microenvironment. Comodifying CAR T cells to secrete different classes of proteins can be used to optimize CAR T cell function, overcome suppressive signals, and/or alter the tumor microenvironment milieu. These modifications aim to improve initial responses to therapy and enhance the durability of response. Furthermore, CAR T cells can deliver these molecules locally to the tumor microenvironment, avoiding systemic distribution. This approach has been tested in preclinical models using a variety of different classes of agonistic and antagonistic proteins, and clinical trials are currently underway to assess efficacy in patients.