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Cytotoxic T lymphocytes (CTLs) targeting Epstein-Barr virus (EBV) proteins appear to be a promising treatment option for patients with aggressive lymphomas.
Researchers tested the autologous CTLs in a cohort of 50 patients with Hodgkin or non-Hodgkin lymphoma.
The treatment produced responses in about 62% of patients with relapsed or refractory disease.
And it sustained remissions in roughly 93% of patients who were at a high risk of relapse.
Catherine Bollard, MD, of the Children’s National Medical Center in Washington, DC, and her colleagues reported these results in the Journal of Clinical Oncology.
The investigators noted that about 40% of lymphoma patients have tumor cells expressing the type II latency EBV antigens latent membrane protein 1 (LMP1) and LMP2. But T cells specific for these antigens are present in low numbers and may not “recognize” the tumors they should attack.
So Dr Bollard and her colleagues decided to test the effects of infusing LMP-directed CTLs into 50 patients with EBV-positive lymphomas.
The researchers used adenoviral vector-transduced dendritic cells and EBV-transformed B–lymphoblastoid cell lines as antigen-presenting cells to activate and expand LMP-specific T cells.
For some patients, the team used an adenoviral vector encoding the LMP2 antigen alone (n=17). And for others, they used a vector encoding both LMP1 and LMP2 (n=33).
Twenty-nine of the patients were in remission when they received CTL infusions, but they were at a high risk of relapse. The remaining 21 patients had relapsed or refractory disease at the time of CTL infusion.
Twenty-seven of the 29 patients who received CTLs as an adjuvant treatment remained in remission from their disease at 3.1 years after treatment.
However, the 2-year event-free survival rate was 82% for this group of patients. None of them died of lymphoma, but 9 died from complications associated with the chemotherapy and radiation they had received.
“That’s why this research is important,” Dr Bollard said. “Patients with lymphomas traditionally have a good cure rate with chemotherapy and radiation. What kills them is the side effects of those treatments—second cancers, lung, and heart disease.”
Of the 21 patients with relapsed or refractory disease, 13 responded to CTL infusions. And 11 patients achieved a complete response.
In this group, the 2-year event-free survival rate was about 50%, regardless of whether patients received CTLs directed against LMP1/2 or LMP2 alone.
The investigators found that responses were associated with effector and central memory LMP1-specific CTLs but not with the patient’s type of lymphoma or lymphopenic status.
Even those patients with limited in vivo expansion of LMP-directed CTLs achieved complete responses. And this effect was associated with epitope spreading.
“This is a targeted therapeutic approach that we hope can be used early in the disease to treat relapse,” Dr Bollard said. “We saw good outcomes here. Eventually, it could be a front-line therapy.”
The researchers noted that the difficulty of tailoring CTLs for each patient has been cited as a barrier to this type of treatment. But currently available treatments can be expensive and induce severe side effects that require hospitalization.
“Although we spend some time making the cells, patients go home with few side effects and few associated hospital costs,” said study author Cliona Rooney, PhD, of the Baylor College of Medicine in Houston, Texas. “It can be less costly than chemotherapy.”
In this study, the investigators did not see any toxicities attributable to CTL infusion. One patient did have CNS deterioration 2 weeks after infusion, but this was attributed to disease progression.
And another patient developed respiratory complications about 4 weeks after a second CTL infusion. But this was attributed to an intercurrent infection, and the patient made a complete recovery. 
Cytotoxic T lymphocytes (CTLs) targeting Epstein-Barr virus (EBV) proteins appear to be a promising treatment option for patients with aggressive lymphomas.
Researchers tested the autologous CTLs in a cohort of 50 patients with Hodgkin or non-Hodgkin lymphoma.
The treatment produced responses in about 62% of patients with relapsed or refractory disease.
And it sustained remissions in roughly 93% of patients who were at a high risk of relapse.
Catherine Bollard, MD, of the Children’s National Medical Center in Washington, DC, and her colleagues reported these results in the Journal of Clinical Oncology.
The investigators noted that about 40% of lymphoma patients have tumor cells expressing the type II latency EBV antigens latent membrane protein 1 (LMP1) and LMP2. But T cells specific for these antigens are present in low numbers and may not “recognize” the tumors they should attack.
So Dr Bollard and her colleagues decided to test the effects of infusing LMP-directed CTLs into 50 patients with EBV-positive lymphomas.
The researchers used adenoviral vector-transduced dendritic cells and EBV-transformed B–lymphoblastoid cell lines as antigen-presenting cells to activate and expand LMP-specific T cells.
For some patients, the team used an adenoviral vector encoding the LMP2 antigen alone (n=17). And for others, they used a vector encoding both LMP1 and LMP2 (n=33).
Twenty-nine of the patients were in remission when they received CTL infusions, but they were at a high risk of relapse. The remaining 21 patients had relapsed or refractory disease at the time of CTL infusion.
Twenty-seven of the 29 patients who received CTLs as an adjuvant treatment remained in remission from their disease at 3.1 years after treatment.
However, the 2-year event-free survival rate was 82% for this group of patients. None of them died of lymphoma, but 9 died from complications associated with the chemotherapy and radiation they had received.
“That’s why this research is important,” Dr Bollard said. “Patients with lymphomas traditionally have a good cure rate with chemotherapy and radiation. What kills them is the side effects of those treatments—second cancers, lung, and heart disease.”
Of the 21 patients with relapsed or refractory disease, 13 responded to CTL infusions. And 11 patients achieved a complete response.
In this group, the 2-year event-free survival rate was about 50%, regardless of whether patients received CTLs directed against LMP1/2 or LMP2 alone.
The investigators found that responses were associated with effector and central memory LMP1-specific CTLs but not with the patient’s type of lymphoma or lymphopenic status.
Even those patients with limited in vivo expansion of LMP-directed CTLs achieved complete responses. And this effect was associated with epitope spreading.
“This is a targeted therapeutic approach that we hope can be used early in the disease to treat relapse,” Dr Bollard said. “We saw good outcomes here. Eventually, it could be a front-line therapy.”
The researchers noted that the difficulty of tailoring CTLs for each patient has been cited as a barrier to this type of treatment. But currently available treatments can be expensive and induce severe side effects that require hospitalization.
“Although we spend some time making the cells, patients go home with few side effects and few associated hospital costs,” said study author Cliona Rooney, PhD, of the Baylor College of Medicine in Houston, Texas. “It can be less costly than chemotherapy.”
In this study, the investigators did not see any toxicities attributable to CTL infusion. One patient did have CNS deterioration 2 weeks after infusion, but this was attributed to disease progression.
And another patient developed respiratory complications about 4 weeks after a second CTL infusion. But this was attributed to an intercurrent infection, and the patient made a complete recovery.
Cytotoxic T lymphocytes (CTLs) targeting Epstein-Barr virus (EBV) proteins appear to be a promising treatment option for patients with aggressive lymphomas.
Researchers tested the autologous CTLs in a cohort of 50 patients with Hodgkin or non-Hodgkin lymphoma.
The treatment produced responses in about 62% of patients with relapsed or refractory disease.
And it sustained remissions in roughly 93% of patients who were at a high risk of relapse.
Catherine Bollard, MD, of the Children’s National Medical Center in Washington, DC, and her colleagues reported these results in the Journal of Clinical Oncology.
The investigators noted that about 40% of lymphoma patients have tumor cells expressing the type II latency EBV antigens latent membrane protein 1 (LMP1) and LMP2. But T cells specific for these antigens are present in low numbers and may not “recognize” the tumors they should attack.
So Dr Bollard and her colleagues decided to test the effects of infusing LMP-directed CTLs into 50 patients with EBV-positive lymphomas.
The researchers used adenoviral vector-transduced dendritic cells and EBV-transformed B–lymphoblastoid cell lines as antigen-presenting cells to activate and expand LMP-specific T cells.
For some patients, the team used an adenoviral vector encoding the LMP2 antigen alone (n=17). And for others, they used a vector encoding both LMP1 and LMP2 (n=33).
Twenty-nine of the patients were in remission when they received CTL infusions, but they were at a high risk of relapse. The remaining 21 patients had relapsed or refractory disease at the time of CTL infusion.
Twenty-seven of the 29 patients who received CTLs as an adjuvant treatment remained in remission from their disease at 3.1 years after treatment.
However, the 2-year event-free survival rate was 82% for this group of patients. None of them died of lymphoma, but 9 died from complications associated with the chemotherapy and radiation they had received.
“That’s why this research is important,” Dr Bollard said. “Patients with lymphomas traditionally have a good cure rate with chemotherapy and radiation. What kills them is the side effects of those treatments—second cancers, lung, and heart disease.”
Of the 21 patients with relapsed or refractory disease, 13 responded to CTL infusions. And 11 patients achieved a complete response.
In this group, the 2-year event-free survival rate was about 50%, regardless of whether patients received CTLs directed against LMP1/2 or LMP2 alone.
The investigators found that responses were associated with effector and central memory LMP1-specific CTLs but not with the patient’s type of lymphoma or lymphopenic status.
Even those patients with limited in vivo expansion of LMP-directed CTLs achieved complete responses. And this effect was associated with epitope spreading.
“This is a targeted therapeutic approach that we hope can be used early in the disease to treat relapse,” Dr Bollard said. “We saw good outcomes here. Eventually, it could be a front-line therapy.”
The researchers noted that the difficulty of tailoring CTLs for each patient has been cited as a barrier to this type of treatment. But currently available treatments can be expensive and induce severe side effects that require hospitalization.
“Although we spend some time making the cells, patients go home with few side effects and few associated hospital costs,” said study author Cliona Rooney, PhD, of the Baylor College of Medicine in Houston, Texas. “It can be less costly than chemotherapy.”
In this study, the investigators did not see any toxicities attributable to CTL infusion. One patient did have CNS deterioration 2 weeks after infusion, but this was attributed to disease progression.
And another patient developed respiratory complications about 4 weeks after a second CTL infusion. But this was attributed to an intercurrent infection, and the patient made a complete recovery.