This week we profile a recent publication in Clinical Microbiology and Infection from Dr. Madeleine Heldman (pictured, left), Kaja Aagaard (right), and the laboratory of Dr. Joshua Hill (center) at Fred Hutch.
Can you provide a brief overview of your lab’s current research focus?
My lab focuses on infectious diseases and immune responses in immunocompromised patients with hematologic malignancies, particularly hematopoietic cell transplant (HCT) recipients and recipients of chimeric antigen receptor-modified T (CAR-T) cell therapies. We are creating a specimen repository to examine humoral and cellular immune responses to pathogens and vaccine antigens in CAR-T therapy recipients. We also lead clinical trials for novel therapies for the treatment and prevention of viral infections in HCT recipients.
What is the significance of the findings in this publication?
Hemopoietic cell and solid organ transplant (SOT) recipients have immune deficits that lead to considerable morbidity and mortality from viral infections. There has been enormous enthusiasm for evaluating immune responses to certain viruses (i.e., cytomegalovirus), but herpes-simplex virus (HSV), varicella-zoster virus (VZV) and human herpesvirus-6 (HHV-6) are seldom the focus of such research. While antivirals are often effective at preventing and treating HSV and VZV following transplant, there are several limitations to long-term antivirals, and management of HHV-6 with currently available antivirals remains challenging. In this review, we discuss the advantages of vaccines and adoptive cellular therapies over antivirals for the management of these infections and potential clinical applications of assays that assess virus-specific adaptive immunity.
What are the next steps for this research?
There are several “unknowns” when it comes to adaptive immunity to these three viruses in transplant recipients. We need assays that can measure cell-mediated immunity to these viruses and that have reliable clinical applicability. For example, in the case of VZV, such assays could aid in determining whether there has been sufficient virus-specific immune reconstitution to discontinue antiviral prophylaxis, which often creates a significant pill burden for patients. Adoptive transfer of virus-specific T-cells is emerging as a promising strategy for the prevention and treatment of viral infections in transplant recipients, and we call for additional initiatives that focus on optimizing these cellular therapies specifically for the management of HSV, VZV, and HHV-6
If you’d like us to mention your funding sources, please list them.
Our research is funded by the National Institute of Allergy and Infectious Diseases and the National Cancer Institute of the National Institutes of Health.
