Cell-based passive immunization for protection against SARS-CoV-2 infection

Abstract

Background Immunologically impaired individuals respond poorly to vaccines, highlighting the need for additional strategies to protect these vulnerable populations from COVID-19. While monoclonal antibodies (mAbs) have emerged as promising tools to manage infectious diseases, the transient lifespan of neutralizing mAbs in patients limits their ability to confer lasting, passive prophylaxis from SARS-CoV-2. Here, we attempted to solve this problem by combining cell and mAb engineering in a way that provides durable immune protection against viral infection using safe and universal cell therapy. Methods Mouse embryonic stem cells equipped with our FailSafe™ and induced allogeneic cell tolerance technologies were engineered to express factors that potently neutralize SARS-CoV-2, which we call ‘neutralizing biologics’ (nBios). We subcutaneously transplanted the transgenic cells into mice and longitudinally assessed the ability of the cells to deliver nBios into circulation. To do so, we quantified plasma nBio concentrations and SARS-CoV-2 neutralizing activity over time in transplant recipients. Finally, using similar cell engineering strategies, we genetically modified FailSafe™ human-induced pluripotent stem cells to express SARS-CoV-2 nBios. Results Transgenic mouse embryonic stem cells engineered for safety and allogeneic-acceptance can secrete functional and potent SARS-CoV-2 nBios. As a dormant, subcutaneous tissue, the transgenic cells and their differentiated derivatives long-term deliver a supply of protective nBio titers in vivo. Moving toward clinical relevance, we also show that human-induced pluripotent stem cells, similarly engineered for safety, can secrete highly potent nBios. Conclusions Together, these findings show the promise and potential of using ‘off-the-shelf’ cell products that secrete neutralizing antibodies for sustained protective immunity against current and future viral pathogens of public health significance.

Genetic predisposition to milder forms of COVID-19 may provide some resilience to head and neck cancers

“…When the immune system is impaired, one of its consequences is an increased susceptibility to severe infections, and another is the non-clearance of viral infections or their asymptomatic carriership. Individuals with compromised immune systems may also display a reduced response to vaccines, emphasizing the importance of additional protective measures ( 28 ). Immunosuppression heightens the likelihood and severity of HNC, with lactic acid-induced immunosuppression mediated by GPNMB and CD44 in the tumor microenvironment contributing to cancer progression.…”