Background The novel coronavirus pandemic has drastically affected healthcare organizations across the globe. Methods We sought to summarize the current telemedicine environment in order to highlight the important changes triggered by the novel coronavirus pandemic, as well as highlight how the current crisis may inform the future of telemedicine.Results At many institutions, the number of telemedicine visits dramatically increased within days following the institution of novel coronavirus pandemic restrictions on in-person clinical encounters. Prior to the pandemic, telemedicine utilization was weak throughout surgical specialties due to regulatory and reimbursement barriers. As part of the pandemic response, the USA government temporarily relaxed various telemedicine restrictions and provided additional telemedicine funding. Discussion The post-pandemic role of telemedicine is dependent on permanent regulatory solutions. In the coming decade, telemedicine and telesurgery are anticipated to mature due to the proliferation of interconnected consumer health devices and high-speed 5G data connectivity.
Purpose
Infusion of interleukin-12 (IL-12) can mediate anti-tumor immunity in animal models, yet its systemic administration to patients with cancer results in minimal efficacy and severe toxicity. Here, we evaluated the anti-tumor activity of adoptively transferred human tumor infiltrating lymphocytes (TIL) genetically engineered to secrete single-chain IL-12 selectively at the tumor site.
Experimental design
Thirty-three patients with metastatic melanoma were treated in a cell-dose escalation trial of autologous TIL transduced with a gene encoding a single chain IL-12 driven by a nuclear factor of activated T cells promoter (NFAT.IL12). No IL-2 was administered.
Results
The administration of 0.001-0.1 X 109 NFAT.IL12 transduced TIL to 17 patients resulted in a single objective response (5.9%). However, at doses between 0.3-3 X 109 cells, 10 of 16 patients (63%) exhibited objective clinical responses. The responses tended to be short and the administered IL-12 producing cells rarely persisted at one month. Increasing cell doses were associated with high serum levels of IL-12 and gamma-interferon as well as clinical toxicities including liver dysfunction, high fevers and sporadic life threatening hemodynamic instability.
Conclusions
In this first-in-man trial, administration of TIL transduced with an inducible IL-12 gene mediated tumor responses in the absence of IL-2 administration using cell doses 10-100 fold lower than conventional TIL. However, due to toxicities, likely attributable to the secreted IL-12, further refinement will be necessary before this approach can be safely utilized in the treatment of cancer patients.
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