CELLULAR IMMUNOTHERAPY OF EBV-ASSOCIATED LYMPHOMAS

We have administered donor-derived EBV-specific CTL lines to patients at high risk of developing EBV lymphoma after a T cell depleted transp lant from a matched unrelated donor or mismatched family member. CTL i nfusion produced a virus-specific immune response to EBV that persiste d for up to three years. None of 50 patients who received prophylactic CTLs have developed EBV-LPD, compared with a cumulative risk of 11% i n patients who did not receive this treatment. Two patients who were t reated for clinically evident EBV-LPD attained prolonged remission aft er CTL infusion and in situ hybridization and semiquantitative PCR sho wed that the gene marked CTL had selectively accumulated at disease si tes. We conclude that EBV-specific CTLs are safe and effective prophyl axis for EBV lymphoma and can also eradicate established disease. This approach is now being extended to other viruses that produce post-tra nsplant morbidity and to other EBV-associated malignancies. In other E BV-associated primary malignancies, tumor cells may be less susceptibl e to immunotherapeutic approaches because they express a more restrict ed array of subdominant EBV-encoded antigens. We have treated five pat ients with relapsed EBV genome positive Hodgkin disease with polyclona l EBV specific CTLs and the infused cells have persisted in peripheral blood for up to 12 weeks and in one patient were detected in a malign ant pleural effusion.