Role of rapidly evolving immunotherapy in chronic active Epstein-Barr virus disease

Abstract

Chronic active Epstein-Barr Virus disease is a kind of Epstein-Barr Virus associated T/NK cell lymphoproliferative disease. At present, there is still a lack of standard therapeutic regimen for its treatment, but its basic treatment principles include controlling inflammatory response, anti-tumor proliferation, and immune reconstitution. Hematopoietic stem cell transplantation is currently the only method that can cure this disease. In recent years, immunotherapy has developed rapidly and is widely used in the treatment of various hematological malignancies; various immunotherapy drugs, including PD-1 inhibitors, have also demonstrated their safety and efficacy in CAEBV, while immune cell therapies such as Epstein- Barr virus-specific T cells have also displayed their unique advantages in CAEBV.

Keywords: Epstein-Barr virus; Epstein-Barr virus specific cytotoxic T lymphocytes; PD-1 inhibitor; chronic active Epstein-Barr virus disease; immunotherapy.

Figure 1

Mechanism and symptoms of chronic active Epstein-Barr virus disease (CAEBV). EBV infects the human body, forming the latent infection in the body. When the immune function of the body is impaired or the virus replication is enhanced, it leads to a variety of EBV positive lymphocyte proliferative diseases, including CAEBV. EBV, Epstein-Barr virus; NK cell, natural killer cell; EBNA1, Epstein-Barr virus nuclear antigen1; LMP, latent membrane protein.

Figure 2

The “three-step” therapy of CAEBV. The first step in the treatment of CAEBV is to control the combined hypercytokinemia by immunosuppressive therapy, the second step is to eliminate EBV-infected T/NK cells as much as possible using combination chemotherapy, and the third step is to achieve reconstitution of immune function by hematopoietic stem cell transplantation. CAEBV, Chronic active Epstein-Barr Virus disease; NK, natural killer; modified CHOP, cyclophosphamide, pirarubicin, vincristine, and prednisolone; ESCAP, etoposide, cytosine arabinoside, L-asparaginase, methylprednisolone, and prednisolone; allo-HSCT, allogeneic hematopoietic stem cell transplantation.

Figure 3

Mechanism underlying treatments used to treat CAEBV. Immunotherapy of CAEBV relies on specific binding between ligands and receptors, antibodies and antigens, resulting in the killing effect of normal immune cells on EBV-infected T/NK cells. PD-1, programmed cell death protein 1; CAR, chimeric antigen receptor; CCR4, cytotoxic T-lymphocyte antigen 4; MHC, major histocompatibility complex; TCR, T cell receptor; CAEBV, chronic active EBV infection.