Anti-EBV Antigen T Cells Fight Lymphoma

Cytotoxic T cell immunotherapy shows promise for patients with lymphoma who are at high risk for relapse or have disease refractory to current treatments

medwireNews: US researchers have used autologous T cells directed against type II latency Epstein–Barr virus (EBV) antigens to successfully maintain or induce remission in patients with high-risk or multiple relapsed EBV-associated lymphoma.

The team expanded cytotoxic T lymphocytes (CTLs) from 50 patients against latent membrane protein (LMP)1 or 2 from autologous Dendritic cells and EBV-transformed cell lines with an adenoviral Vector expressing LMP2 (n=17) or LMP2 plus ΔLMP1 (n=33).

The patients were given CTLs as an adjuvant treatment via infusion on initial remission of disease due to a high risk of relapse (n=12) or while in remission after between one and six relapses (n=17), or for relapsed or resistant disease not responsive to standard therapy (n=21).

Twenty-eight of the 29 high-risk or multiple-relapse patients receiving LMP-CTLs as adjuvant therapy remained in remission at a median of 3.1 years after infusion. One patient died within 8 weeks of treatment, before evaluation, from pre-existing cardiovascular disease.

However, event-free survival (EFS) was just 82% due to nine deaths from nonrelapse-related causes, mostly associated with complications from previously administered extensive chemoradiotherapy, report Catherine Bollard, from Baylor College of Medicine in Houston, Texas, USA, and co-authors.

In addition, 11 of the 21 patients with active disease achieved complete remission and two patients achieved a partial remission, with a 2-year EFS rate of 50%.

Of note, EFS rates in both patient populations did not significantly differ between patients given LMP2 or LMP2 plus ΔLMP1 CTLs.

But complete remission was associated with the spread of CTLs against LMP, and nonviral tumour antigens, in the peripheral blood 2 months after CTL infusion, the team reports.

“[W]e have shown that it is possible to resurrect powerful immunity to subdominant tumor-associated viral antigens in heavily pretreated patients with lymphoma,” write Catherine Bollard and colleagues in the Journal of Clinical Oncology.

“Our results suggest that such targeted therapies have a place not only in eliminating chemoradiotherapy-resistant malignant cell populations in relapsed patients but also in preventing relapse and achieving durable remissions without off-target adverse effects or long-term toxicities when administered early in the disease process.”

Reference

Bollard CM, Gottschalk S, Torrano V, et al. Sustained Complete Responses in Patients With Lymphoma Receiving Autologous Cytotoxic T Lymphocytes Targeting Epstein-Barr Virus Latent Membrane Proteins. J Clin Oncol 2013 December 16. [Epub ahead of print].

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