  
Early results with immunotherapy for relapsed Hodgkin disease encouraging
Last Updated: 2001-04-26 18:48:54 EDT (Reuters Health)
WESTPORT, CT (Reuters Health) - Epstein Barr virus (EBV)-specific cytotoxic T lymphocytes have shown promise in the treatment of relapsed EBV-positive Hodgkin disease, researchers reported at the Fifth International AIDS Malignancy Conference in Bethesda, Maryland.
Dr. Cliona Rooney and colleagues of Baylor College of Medicine in Houston, in the preliminary stages of a dose-escalation trial, have observed mixed tumor responses in 11 Hodgkin disease patients treated with infusions of EBV-specific cytotoxic T lymphocytes. Nodes have disappeared in some cases, and three patients remain stable after 10 months of therapy, Dr. Rooney told Reuters Health.
"What we've seen is a decrease in viral load in the peripheral blood, an increase in immunity to EBV proteins expressed in tumor cells, and homing of the cytotoxic T cells to tumor tissues," Dr. Rooney said.
Previously, the researchers used a lymphoblastoid transformed B-cell line to generate the cytotoxic T cells. A problem with that, according to Dr. Rooney, is that this cell line expresses nine virus proteins, whereas the Hodgkin tumors express only four.
"So what we are doing now is activating T cells using just the proteins in the Hodgkin tumor cells," she said. "Hopefully that will mean that the T cells we infuse will be more specific for the tumor."
"In the future we want to make the cytotoxic T lymphocytes genetically more resistant to inhibitory molecules secreted by the tumor cells," Dr. Rooney added. To that end, the researchers have rendered T cells resistant to transforming growth factor (TGF) through retroviral expression of a mutant TGF receptor.
They are also exploring ways to counter the downregulation of immunodominant EBV antigens and the secretion of interleukin-10.
Other researchers have successfully used this type of immunotherapy against HIV, Dr. Rooney noted. Her group's preparation can be used specifically to treat Hodgkin tumors that arise in HIV-infected patients because of immunosuppression, she said.
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