T-cell immunotherapy for prevention of COVID-19 following bone marrow transplantation
Michael Keller
MDChildren's Research Institute
Project Term: July 1, 2021 - June 30, 2024
SARS-Cov-2 infections may be prolonged in cancer patients and may enable intrahost development of virulent viral variants. Adoptive immunotherapy with virus-specific T-cells has been an effective treatment for refractory viral infections in immunocompromised patients following HSCT. We propose to study the functionality of coronavirus-specific T-cells (CSTs) from healthy donors, and utilize CSTs as preventative therapy for patients undergoing bone marrow transplant in a phase I study.
Immunocompromised patients including those with cancer and those who have undergone bone marrow transplantation may be at higher risk for prolonged and possibly severe infections with COVID-19. Studies suggest that prolonged infections with COVID-19 may allow viral mutations to occur in a person, and cause resistant or more dangerous versions of the virus to spread. Susceptibility to viruses in patients with cancer is largely due to a weakened immune system, and particularly due to weak immune cells that fight viruses (T-cells). Infusion of virus-fighting T-cells from healthy individuals to those who are immunocompromised has been used successfully in many prior studies. T-cell immunity against SARS-CoV-2 (the virus that causes COVID-19) has been documented in most healthy individuals who recover from infection. We have shown that it is feasible to grow T-cells targeting SARS-CoV-2 in the laboratory, and that they recognize many viral proteins. We propose to study the function of these coronavirus-specific T-cells to ensure that they have strong virus-fighting ability, and also determine if they can recognize new SARS-CoV-2 variant viruses (including the UK and South Africa strains). We then plan to test preventative T-cell infusion in patients who have undergone bone marrow transplant for cancer to determine if we can provide immunity against COVID-19 to immunocompromised patients. We are hopeful that this will provide initial data for a larger trial of T-cell therapy against COVID-19, and provide protection to cancer patients who may be at risk for COVID-19 infection.