T cell immunotherapies have shown great success in the prevention and treatment of viral infections (most particularly Epstein-Barr virus [EBV], adenovirus and cytomegalovirus [CMV]) in post-hematopoietic stem cell transplant, with no major adverse events. The team recently published a novel study using CMV seronegative donors to prime virus-specific responses. The team discovered that:
- Naïve T cells can be primed in vitro with specificity for multiple viruses.
- The virus-specific T cell immune responses are not derived from contaminating maternal cells and are not affected by the serostatus of the mother.
- CMV-specific T cells primed from cord blood recognize highly unique and novel CMV epitopes not typically seen in memory CMV-specific T cells.
- These observations are a direct consequence of the clonal diversity of T cells derived from naïve T cells rather than memory-derived T cells.
Efforts are now underway to expand the targeted viral antigens (e.g., extend to HPV, HHV6, BKV, HIV) and the immune-compromised patients eligible to receive those products (through third-party T cell banking and generating cells from naïve donors). For example, the team recently has shown that it can generate HIV-specific T cells from HIV+ individuals and to date, two patients have been treated with this novel cell therapy. The team also plans to test viral targets in other pathogens, such as Ebola and influenza.
In summary, this group is continuing with clinical trials targeting viruses in immune-compromised patients post-stem cell transplant and patients with primary immune deficiency. The group was recently awarded the highly prestigious UM1 Martin Delaney Collaborative Grant through the NIH, which supports research focused on an HIV cure. Titled “BELIEVE: Bench to Bed Enhanced Lymphocyte Infusions to Engineer Viral Eradication,” the grant is led by Doug Nixon, M.D., Ph.D., Catherine Bollard, M.B.Ch.B, M.D., Brad Jones, Ph.D., and Alan Greenberg, M.D., M.P.H., from the Department of Microbiology, Immunology and Tropical Medicine at the George Washington University. Finally, Michael Keller, M.D., is leading an effort with the PBMTC to use third-party, multivirus-specific T cells to treat viral infections in pediatric patients after blood and marrow transplant (BMT).