Reprinted with the kind permission of the HHV-6 Foundation.
Baylor College of Medicine’s Center for Cell and Gene Therapy has demonstrated a way to quickly generate antiviral T cells for the treatment of opportunistic viral infections, and recently reported success in a small clinical trial. While bone marrow and stem cell transplantation have become increasingly common interventions for patients with cancer, blood disorders, and genetic diseases, these patients are still at risk for a variety of complications including opportunistic viral infections that have no specific treatments available. Their novel therapy utilizes synthetic peptides to generate single T cell lines from stem cell donors, which consistently have specificity for up to five viruses (AdV, EBV, CMV, BKV, and HHV6) representing the most frequent causes of viral morbidity and mortality after HSCT.
This technique, called “adoptive transfer of virus-specific T cells (VSTs),” can be safe and effective, and offers many advantages over conventional antiviral treatment options because there is no toxicity and it can be used for patients infected with strains that are resistant to commonly used antivirals. Unfortunately, the cells themselves have historically been complex to prepare and limited in their antiviral range. However, after years of work that included development of an enhanced adoptive T cell immunotherapy specific to HHV-6B, as well as refining an immunotherapy technique for limiting the effects of EBV and a set of eleven viruses known to cause complications following hematopoietic stem cell transplantation (HSCT), this group’s novel approach now demonstrates the feasibility and clinical utility of rapidly generated single-culture VSTs .
The clinical trial targeted 12 immunogenic antigens from five viruses (EBV, AdV, CMV, BKV, and HHV-6). Intractable CMV, EBV, and AdV infections have previously proved to be responsive to adoptive T cell transfer, but this is the first clinical trial that targeted both BKV and HHV-6, both of which are ubiquitous viruses that may cause severe and intractable disease in HSCT recipients. When administered to 11 recipients of allogeneic transplants in the current study, 8 of whom had up to four active infections with the targeted viruses, these VSTs proved safe in all subjects and produced an overall 94% virological and clinical response rate that was sustained long-term (15 complete and 2 partial responses).
With their new technology, the team can produce cells capable of destroying multiple infections at once in only 10 days. Previous methods took three months to manufacture and typically focused on only one virus. This therapeutic approach of isolating, treating and injecting patients with T cells may eventually prove to be the safest and most cost-effective alternative for immunocompromised patients with severe viral infections. The same immunotherapy technique has also been applied to advanced cervical cancer. Investigators reported in June that a single infusion of HPV-targeted T cell therapy induced a complete remission in two patients with advanced metastatic cervical cancer.
The authors also remark that there are many factors that cause transplant patients to be vulnerable to endogenous (latent) and exogenous (community acquired) viruses, including the cytotoxic drugs administered during the conditioning phase, the delay in immune recovery after the transplant, and the immunosuppressive drugs administered to prevent GVHD. There are currently no FDA approved rugs for the treatment of HHV-6, BK virus, adenovirus or EBV.
: Papadopoulou A, Gerdemann U, Katari UL, Tzannou I, Liu H, Martinez C, Leung K, Carrum G, Gee AP, Vera JF, Krance RA, Brenner MK, Rooney CM1, Heslop HE, Leen AM. Activity of broad-spectrum T cells as treatment for AdV, EBV, CMV, BKV, and HHV6 infections after HSCT. Sci Transl Med. 2014 Jun 25;6(242):242ra83. doi: 10.1126/scitranslmed.3008825