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NEW ORLEANS—Results of a phase 1 trial suggest that modified T cells can fight infection in patients who have undergone haploidentical hematopoietic
stem cell transplant (haplo-HSCT), and subsequent administration of a bio-inert drug can ameliorate graft-vs-host disease (GVHD) in these patients.
Researchers introduced the suicide gene inducible caspase 9 (iC9) into T cells and infused them into transplant recipients to promote immune reconstitution.
For patients who went on to develop GVHD, the researchers activated the suicide gene by administering a dose of the drug rimiducid (AP1903).
This cleared the patients of GVHD symptoms without jeopardizing the remaining T cells’ ability to fight infection.
The researchers presented these results at the American Society of Gene and Cell Therapy Annual Meeting and reported them in Blood.
The trial was sponsored by Baylor College of Medicine, but Bellicum Pharmaceuticals is the company developing rimiducid and the so-called iC9 “safety switch,” also known as CaspaCIDe.
“We’ve shown that the therapy works, fighting viruses that threaten immune-compromised patients,” said Xiaoou Zhou, PhD, of Baylor College of Medicine in Houston, Texas.
“We have also shown that the switch can turn off the T cells that reproduce out of control, attacking the patient’s graft-vs-host disease. This study was the first to look at any potential effect on the ability of the T cells to fight infection. We found there was no compromise.”
The study included 12 patients with a median age of 10 (range, 2-50) who had undergone haplo-HSCT. They received donor-derived T cells engineered with CaspaCIDe using a dose escalation schedule from 1×104 to 5×106 cells/kg, at a median of 42 days after transplant (range, 31-82 days).
All 12 patients had more rapid immune reconstitution and fewer infections after the infusions, when compared with previously reported results in T-cell-depleted, haplo-HSCT procedures. The CaspaCIDe T cells successfully provided protection from EBV, CMV, VZV, HHV6, and BKV viruses.
The researchers said there were no immediate toxicities related to the T-cell infusions, but 4 patients went on to develop GVHD.
Treatment with rimiducid resolved the patients’ GVHD symptoms within 6 to 48 hours. The researchers found that rimiducid could eliminate the uncontrolled T cells in the central nervous system as well as the peripheral blood.
Even after the problematic T cells were killed, the remaining T cells were able to fight infection without causing further GVHD.
One patient experienced a decrease in cell counts after receiving rimiducid, but counts had normalized by 48 hours. The researchers said there were no other immediate or delayed adverse effects associated with the drug.
One patient developed cytokine release syndrome, but this was resolved in 2 hours with a single dose of rimiducid.
“This study shows that infusing larger numbers of haploidentical donor T cells engineered with CaspaCIDe leads to better infection control,” Dr Zhou said. “We also showed that, if GVHD occurs, it can be rapidly controlled and eliminated by removing alloreactive cells with rimiducid in vivo, and that the productive, antiviral and anticancer cells remain, repopulate, and maintain immunity.”
“This is a significant finding that can lead to broader adoption of curative haploidentical transplants for cancers and genetic blood disorders. It also suggests that CaspaCIDe has great potential with CAR T and TCR therapies, where rapid control of dangerous T-cell-mitigated toxicities, such as cytokine release syndrome, is needed to achieve wide adoption.” 
Image courtesy of NIAID
NEW ORLEANS—Results of a phase 1 trial suggest that modified T cells can fight infection in patients who have undergone haploidentical hematopoietic
stem cell transplant (haplo-HSCT), and subsequent administration of a bio-inert drug can ameliorate graft-vs-host disease (GVHD) in these patients.
Researchers introduced the suicide gene inducible caspase 9 (iC9) into T cells and infused them into transplant recipients to promote immune reconstitution.
For patients who went on to develop GVHD, the researchers activated the suicide gene by administering a dose of the drug rimiducid (AP1903).
This cleared the patients of GVHD symptoms without jeopardizing the remaining T cells’ ability to fight infection.
The researchers presented these results at the American Society of Gene and Cell Therapy Annual Meeting and reported them in Blood.
The trial was sponsored by Baylor College of Medicine, but Bellicum Pharmaceuticals is the company developing rimiducid and the so-called iC9 “safety switch,” also known as CaspaCIDe.
“We’ve shown that the therapy works, fighting viruses that threaten immune-compromised patients,” said Xiaoou Zhou, PhD, of Baylor College of Medicine in Houston, Texas.
“We have also shown that the switch can turn off the T cells that reproduce out of control, attacking the patient’s graft-vs-host disease. This study was the first to look at any potential effect on the ability of the T cells to fight infection. We found there was no compromise.”
The study included 12 patients with a median age of 10 (range, 2-50) who had undergone haplo-HSCT. They received donor-derived T cells engineered with CaspaCIDe using a dose escalation schedule from 1×104 to 5×106 cells/kg, at a median of 42 days after transplant (range, 31-82 days).
All 12 patients had more rapid immune reconstitution and fewer infections after the infusions, when compared with previously reported results in T-cell-depleted, haplo-HSCT procedures. The CaspaCIDe T cells successfully provided protection from EBV, CMV, VZV, HHV6, and BKV viruses.
The researchers said there were no immediate toxicities related to the T-cell infusions, but 4 patients went on to develop GVHD.
Treatment with rimiducid resolved the patients’ GVHD symptoms within 6 to 48 hours. The researchers found that rimiducid could eliminate the uncontrolled T cells in the central nervous system as well as the peripheral blood.
Even after the problematic T cells were killed, the remaining T cells were able to fight infection without causing further GVHD.
One patient experienced a decrease in cell counts after receiving rimiducid, but counts had normalized by 48 hours. The researchers said there were no other immediate or delayed adverse effects associated with the drug.
One patient developed cytokine release syndrome, but this was resolved in 2 hours with a single dose of rimiducid.
“This study shows that infusing larger numbers of haploidentical donor T cells engineered with CaspaCIDe leads to better infection control,” Dr Zhou said. “We also showed that, if GVHD occurs, it can be rapidly controlled and eliminated by removing alloreactive cells with rimiducid in vivo, and that the productive, antiviral and anticancer cells remain, repopulate, and maintain immunity.”
“This is a significant finding that can lead to broader adoption of curative haploidentical transplants for cancers and genetic blood disorders. It also suggests that CaspaCIDe has great potential with CAR T and TCR therapies, where rapid control of dangerous T-cell-mitigated toxicities, such as cytokine release syndrome, is needed to achieve wide adoption.”
Image courtesy of NIAID
NEW ORLEANS—Results of a phase 1 trial suggest that modified T cells can fight infection in patients who have undergone haploidentical hematopoietic
stem cell transplant (haplo-HSCT), and subsequent administration of a bio-inert drug can ameliorate graft-vs-host disease (GVHD) in these patients.
Researchers introduced the suicide gene inducible caspase 9 (iC9) into T cells and infused them into transplant recipients to promote immune reconstitution.
For patients who went on to develop GVHD, the researchers activated the suicide gene by administering a dose of the drug rimiducid (AP1903).
This cleared the patients of GVHD symptoms without jeopardizing the remaining T cells’ ability to fight infection.
The researchers presented these results at the American Society of Gene and Cell Therapy Annual Meeting and reported them in Blood.
The trial was sponsored by Baylor College of Medicine, but Bellicum Pharmaceuticals is the company developing rimiducid and the so-called iC9 “safety switch,” also known as CaspaCIDe.
“We’ve shown that the therapy works, fighting viruses that threaten immune-compromised patients,” said Xiaoou Zhou, PhD, of Baylor College of Medicine in Houston, Texas.
“We have also shown that the switch can turn off the T cells that reproduce out of control, attacking the patient’s graft-vs-host disease. This study was the first to look at any potential effect on the ability of the T cells to fight infection. We found there was no compromise.”
The study included 12 patients with a median age of 10 (range, 2-50) who had undergone haplo-HSCT. They received donor-derived T cells engineered with CaspaCIDe using a dose escalation schedule from 1×104 to 5×106 cells/kg, at a median of 42 days after transplant (range, 31-82 days).
All 12 patients had more rapid immune reconstitution and fewer infections after the infusions, when compared with previously reported results in T-cell-depleted, haplo-HSCT procedures. The CaspaCIDe T cells successfully provided protection from EBV, CMV, VZV, HHV6, and BKV viruses.
The researchers said there were no immediate toxicities related to the T-cell infusions, but 4 patients went on to develop GVHD.
Treatment with rimiducid resolved the patients’ GVHD symptoms within 6 to 48 hours. The researchers found that rimiducid could eliminate the uncontrolled T cells in the central nervous system as well as the peripheral blood.
Even after the problematic T cells were killed, the remaining T cells were able to fight infection without causing further GVHD.
One patient experienced a decrease in cell counts after receiving rimiducid, but counts had normalized by 48 hours. The researchers said there were no other immediate or delayed adverse effects associated with the drug.
One patient developed cytokine release syndrome, but this was resolved in 2 hours with a single dose of rimiducid.
“This study shows that infusing larger numbers of haploidentical donor T cells engineered with CaspaCIDe leads to better infection control,” Dr Zhou said. “We also showed that, if GVHD occurs, it can be rapidly controlled and eliminated by removing alloreactive cells with rimiducid in vivo, and that the productive, antiviral and anticancer cells remain, repopulate, and maintain immunity.”
“This is a significant finding that can lead to broader adoption of curative haploidentical transplants for cancers and genetic blood disorders. It also suggests that CaspaCIDe has great potential with CAR T and TCR therapies, where rapid control of dangerous T-cell-mitigated toxicities, such as cytokine release syndrome, is needed to achieve wide adoption.”