Virus-specific T cell therapy to treat refractory viral infections in solid organ transplant recipients.

Solid organ transplant recipients require ongoing immunosuppression to prevent acute rejection, which puts them at risk of opportunistic infections. Viral infections are particularly challenging to prevent and treat as many establish latency and thus cannot be eliminated, whereas targets for small molecule antiviral medications are limited. Resistance to antivirals and unacceptable toxicity also complicate treatment. Virus-specific T cell therapies aim to restore host-specific immunity to opportunistic viruses that is lacking due to ongoing immunosuppressive therapy. This minireview will provide a state-of-the-art update of the current virus-specific T cell pipeline and translational research that is likely to lead to further treatment options for viral infections in solid organ transplant recipients.

Antiviral cellular therapy for enhancing T-cell reconstitution before or after hematopoietic stem cell transplantation (ACES): a two-arm, open label phase II interventional trial of pediatric patients with risk factor assessment.

Viral infections remain a major risk in immunocompromised pediatric patients, and virus-specific T cell (VST) therapy has been successful for treatment of refractory viral infections in prior studies. We performed a phase II multicenter study (NCT03475212) for the treatment of pediatric patients with inborn errors of immunity and/or post allogeneic hematopoietic stem cell transplant with refractory viral infections using partially-HLA matched VSTs targeting cytomegalovirus, Epstein-Barr virus, or adenovirus. Primary endpoints were feasibility, safety, and clinical responses (>1 log reduction in viremia at 28 days). Secondary endpoints were reconstitution of antiviral immunity and persistence of the infused VSTs. Suitable VST products were identified for 75 of 77 clinical queries. Clinical responses were achieved in 29 of 47 (62%) of patients post-HSCT including 73% of patients evaluable at 1-month post-infusion, meeting the primary efficacy endpoint (>52%). Secondary graft rejection occurred in one child following VST infusion as described in a companion article. Corticosteroids, graft-versus-host disease, transplant-associated thrombotic microangiopathy, and eculizumab treatment correlated with poor response, while uptrending absolute lymphocyte and CD8 T cell counts correlated with good response. This study highlights key clinical factors that impact response to VSTs and demonstrates the feasibility and efficacy of this therapy in pediatric HSCT.