Treatment of nasopharyngeal carcinoma with Epstein-Barr virus–specific T lymphocytes

Abstract

Conventional treatment for nasopharyngeal carcinoma (NPC) frequently fails and is accompanied by severe long-term side effects. Since virtually all undifferentiated NPCs are associated with Epstein-Barr virus (EBV), this tumor is an attractive candidate for cellular immunotherapy targeted against tumor-associated viral antigens. We now demonstrate that EBVspecific cytotoxic T-cell (CTL) lines can readily be generated from individuals with NPC, notwithstanding the patients' prior exposure to chemotherapy/radiation. A total of 10 patients diagnosed with advanced NPC were treated with autologous CTLs. All patients tolerated the CTLs, although one developed increased swelling at the site of pre-existing disease. At 19 to 27 months after infusion, 4 patients treated in remission from locally advanced disease remain disease free. Of 6 patients with refractory disease prior to treatment, 2 had complete responses, and remain in remission over 11 to 23 months after treatment; 1 had a partial remission that persisted for 12 months; 1 has had stable disease for more than 14 months; and 2 had no response. These results demonstrate that administration of EBVspecific CTLs to patients with advanced NPC is feasible, appears to be safe, and can be associated with significant antitumor activity. (Blood. 2005;105:1898-1904

Epstein‐Barr virus (EBV) latent membrane protein‐1‐specific cytotoxic T lymphocytes targeting EBV‐carrying natural killer cell malignancies

“…Extension of a similar strategy to other EBV-associated malignancies, such as HD [14] and NPC [15], has been reported to be efficacious in some patients. However, the majority of lymphoblastoid cell line (LCL)-activated CTL used in the reported studies were directed to immunodominant EBNA3A, EBNA3B, and EBNA3C Ag, which are not expressed in the malignant cells of HD and NPC cases.…”

“…A subdominant portion of LCL-activated CTL may recognize peptides derived from LMP2 [14,15], which would contribute to immunotherapeutic effects in treated patients. However, T cells directing LMP1 peptides are rare [15], reflecting a low CTL precursor frequency [16].…”

“…However, T cells directing LMP1 peptides are rare [15], reflecting a low CTL precursor frequency [16]. To selectively activate the T cell repertoire specific to subdominant EBV Ag, Lin et al [17] used monocyte-derived DC pulsed with LMP2 peptides to immunize NPC patients.…”

Immunotherapy of Epstein-Barr Virus Associated Malignancies Using Mycobacterial HSP70 and LMP2A356–364 Epitope Fusion Protein

“…Moreover, there is a growing emphasis on enhancing the immunogenicity of peptide-based vaccine, such as development of effective human adjuvants and peptide vaccine delivery systems (34). Previous clinical trials and animal experiments have used oil-emulsion-type adjuvant, but this traditional adjuvant has shown serious side effects (12,15). Here we have produced a fusion protein containing a conserved LMP2A epitope and the MtHsp70, which offers a strategy to elicit the anti-tumor immunity of specific CTLs.…”

“…Furthermore, many clinical trials on LMP2A epitope based vaccines have been carried out in the past years. However, moderate or low responses have been observed in human trials and animal model tests (12)(13)(14)(15). One reason might be the poor immunogenicity of the LMP2A derived peptides.…”