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for Cell and Gene Therapy
at Baylor College of Medicine
New virus-specific T-cells (VSTs) can effectively target multiple viruses, thereby clearing and preventing infections in transplant recipients, researchers have reported in Science Translational Medicine.
VSTs have proven effective in previous studies, but they are typically costly, can take months to produce, and often target a single virus.
The new VSTs took about 10 days to produce, are more cost-effective than standard therapy, and can target up to 5 viruses, according to the researchers.
Ann Leen, PhD, of the Baylor College of Medicine in Houston, and her colleagues developed the technique to produce the VSTs, which can target Epstein-Barr virus (EBV), adenovirus (ADV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV6).
“Unlike conventional antiviral drugs, our therapy improves virus-specific T-cell immunity—the root cause of post-transplant viral infections—providing both an effective and safe strategy to treat viruses,” Dr Leen said.
“Additionally, we can readily produce both individualized products and T-cell banks for third-party use, facilitating the extension of T-cell therapy to a standard of care for transplant recipients.”
The researchers generated 48 VST cell lines by stimulating peripheral blood mononuclear cells from allogeneic donors with overlapping peptide libraries that incorporate EBV, CMV, ADV, BKV, and HHV6 antigens.
The team then tested these VSTs in 11 patients who had received allogeneic transplants to treat leukemia, lymphoma, sickle cell disease, and other hematologic and immunodeficient disorders.
Eight of the patients had up to 4 active infections with the targeted viruses. Three patients received the VSTs to prevent infection.
The VSTs produced an overall 94% virological and clinical response that was sustained long-term. Of the 3 patients who received VSTs prophylactically, all remained free of infection for more than 3 months after infusion.
There were no immediate infusion-related toxicities. One patient developed de novo graft-vs-host disease of the skin that improved with topical steroids.
Two patients who received VSTs as prophylaxis developed transplant-associated microangiopathy, but the researchers considered this to be unrelated to VST infusion.
They noted that this is the first time BKV and HHV6 reactivations have been controlled using VSTs. Dr Leen’s team had previously reported promising results with VSTs targeting EBV, CMV, and ADV.
“This study translated improved manufacturing techniques developed in Dr Leen’s laboratory to the clinic and showed that virus-specific T cells produced with the new method could target new viruses and be ready for clinical use after 10 days,” said Helen Heslop, MD, also of Baylor College of Medicine.
“These advances mean that this therapy could be available for more patients to treat viral infections and provide long-lasting protection.” 
for Cell and Gene Therapy
at Baylor College of Medicine
New virus-specific T-cells (VSTs) can effectively target multiple viruses, thereby clearing and preventing infections in transplant recipients, researchers have reported in Science Translational Medicine.
VSTs have proven effective in previous studies, but they are typically costly, can take months to produce, and often target a single virus.
The new VSTs took about 10 days to produce, are more cost-effective than standard therapy, and can target up to 5 viruses, according to the researchers.
Ann Leen, PhD, of the Baylor College of Medicine in Houston, and her colleagues developed the technique to produce the VSTs, which can target Epstein-Barr virus (EBV), adenovirus (ADV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV6).
“Unlike conventional antiviral drugs, our therapy improves virus-specific T-cell immunity—the root cause of post-transplant viral infections—providing both an effective and safe strategy to treat viruses,” Dr Leen said.
“Additionally, we can readily produce both individualized products and T-cell banks for third-party use, facilitating the extension of T-cell therapy to a standard of care for transplant recipients.”
The researchers generated 48 VST cell lines by stimulating peripheral blood mononuclear cells from allogeneic donors with overlapping peptide libraries that incorporate EBV, CMV, ADV, BKV, and HHV6 antigens.
The team then tested these VSTs in 11 patients who had received allogeneic transplants to treat leukemia, lymphoma, sickle cell disease, and other hematologic and immunodeficient disorders.
Eight of the patients had up to 4 active infections with the targeted viruses. Three patients received the VSTs to prevent infection.
The VSTs produced an overall 94% virological and clinical response that was sustained long-term. Of the 3 patients who received VSTs prophylactically, all remained free of infection for more than 3 months after infusion.
There were no immediate infusion-related toxicities. One patient developed de novo graft-vs-host disease of the skin that improved with topical steroids.
Two patients who received VSTs as prophylaxis developed transplant-associated microangiopathy, but the researchers considered this to be unrelated to VST infusion.
They noted that this is the first time BKV and HHV6 reactivations have been controlled using VSTs. Dr Leen’s team had previously reported promising results with VSTs targeting EBV, CMV, and ADV.
“This study translated improved manufacturing techniques developed in Dr Leen’s laboratory to the clinic and showed that virus-specific T cells produced with the new method could target new viruses and be ready for clinical use after 10 days,” said Helen Heslop, MD, also of Baylor College of Medicine.
“These advances mean that this therapy could be available for more patients to treat viral infections and provide long-lasting protection.”
for Cell and Gene Therapy
at Baylor College of Medicine
New virus-specific T-cells (VSTs) can effectively target multiple viruses, thereby clearing and preventing infections in transplant recipients, researchers have reported in Science Translational Medicine.
VSTs have proven effective in previous studies, but they are typically costly, can take months to produce, and often target a single virus.
The new VSTs took about 10 days to produce, are more cost-effective than standard therapy, and can target up to 5 viruses, according to the researchers.
Ann Leen, PhD, of the Baylor College of Medicine in Houston, and her colleagues developed the technique to produce the VSTs, which can target Epstein-Barr virus (EBV), adenovirus (ADV), cytomegalovirus (CMV), BK virus (BKV), and human herpesvirus 6 (HHV6).
“Unlike conventional antiviral drugs, our therapy improves virus-specific T-cell immunity—the root cause of post-transplant viral infections—providing both an effective and safe strategy to treat viruses,” Dr Leen said.
“Additionally, we can readily produce both individualized products and T-cell banks for third-party use, facilitating the extension of T-cell therapy to a standard of care for transplant recipients.”
The researchers generated 48 VST cell lines by stimulating peripheral blood mononuclear cells from allogeneic donors with overlapping peptide libraries that incorporate EBV, CMV, ADV, BKV, and HHV6 antigens.
The team then tested these VSTs in 11 patients who had received allogeneic transplants to treat leukemia, lymphoma, sickle cell disease, and other hematologic and immunodeficient disorders.
Eight of the patients had up to 4 active infections with the targeted viruses. Three patients received the VSTs to prevent infection.
The VSTs produced an overall 94% virological and clinical response that was sustained long-term. Of the 3 patients who received VSTs prophylactically, all remained free of infection for more than 3 months after infusion.
There were no immediate infusion-related toxicities. One patient developed de novo graft-vs-host disease of the skin that improved with topical steroids.
Two patients who received VSTs as prophylaxis developed transplant-associated microangiopathy, but the researchers considered this to be unrelated to VST infusion.
They noted that this is the first time BKV and HHV6 reactivations have been controlled using VSTs. Dr Leen’s team had previously reported promising results with VSTs targeting EBV, CMV, and ADV.
“This study translated improved manufacturing techniques developed in Dr Leen’s laboratory to the clinic and showed that virus-specific T cells produced with the new method could target new viruses and be ready for clinical use after 10 days,” said Helen Heslop, MD, also of Baylor College of Medicine.
“These advances mean that this therapy could be available for more patients to treat viral infections and provide long-lasting protection.”