Abstract
Autologous LMP1/2-specific T cells are safe and show antitumor activity in EBV-positive lymphoma.
Major finding: Autologous LMP1/2-specific T cells are safe and show antitumor activity in EBV-positive lymphoma.
Approach: Patient-derived CTLs targeting the EBV type II latency LMP antigens were expanded ex vivo.
Impact: Infusion of LMP-CTLs prolongs remission and induces durable complete responses without toxicity.
A large percentage of patients with Hodgkin and non-Hodgkin lymphoma express Epstein–Barr virus (EBV) type II latency antigens, including latent membrane protein 1 (LMP1) and LMP2, suggesting that these antigens may be effective immunotherapy targets. However, the frequency and activity of LMP-specific T cells in patients with these tumors is often low. To overcome these limitations, Bollard and colleagues expanded LMP-targeting cytotoxic T lymphocytes (CTL) from patients with EBV-associated Hodgkin or non-Hodgkin lymphoma ex vivo using antigen-presenting cells expressing LMP2 alone or both LMP1 and LMP2. This approach generated effector memory and central memory T cells that exhibited LMP-specific cytotoxic activity. Autologous LMP-CTLs were then administered to 50 patients with EBV-positive lymphoma, and event-free survival (EFS) was assessed. Among 29 patients in remission after multiple relapses or who were at high risk for relapse, adjuvant CTL therapy resulted in sustained remission and a 2-year EFS rate of 82%. In addition, infusion of LMP-CTLs induced 11 complete responses and 2 partial responses in 21 patients with active lymphoma who had experienced tumor relapse following conventional therapy. Antitumor responses following CTL therapy were associated with an increase in circulating LMP-specific T cells in responding patients. Furthermore, 4 of 7 responding patients analyzed exhibited a broader antitumor immune response characterized by activation of T cells specific for lymphoma-associated antigens, indicative of epitope spreading. No toxicities related to CTL infusion or deaths from lymphoma occurred; in contrast, several patients died of non–relapse-related complications resulting from prior chemoradiotherapy. These results show that administration of autologous LMP-specific CTLs results in durable clinical responses in heavily pretreated patients with EBV-positive lymphoma and suggest that this targeted immunotherapy may prevent relapse and limit off-target toxicities associated with conventional chemoradiotherapy.
Note: Research Watch is written by Cancer Discovery Science Writers. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://CDnews.aacrjournals.org.
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