Oncolytic Viruses in Lymphoma Treatment
Introduction of Lymphoma
Lymphoma is a type of blood cancer that begins in lymphocytes. Lymphocytes are a group of immune cells that play a significant role in mediating immune responses against various infections. Lymphocytes can be found in most parts of the human body, such as the spleen, bone marrow, as well as lymph nodes. Based on different origin site of lymphocytes, they have been divided into many subtypes. Among them, Hodgkin's lymphomas (HL) and non-Hodgkin lymphomas (NHL) are common types in patients. Moreover, approximately 90% of lymphomas are non-Hodgkin lymphomas. Signs and symptoms of lymphoma consist of weight loss, fever, night sweats, fatigue, and bleeding. Pilot studies have demonstrated that people with a family history or Epstein-Barr virus infection, or autoimmune diseases have an increased risk for lymphomas.
Standard Therapy for Lymphoma
Currently, some strategies have been developed for the treatment of lymphoma. A wide variety of factors that determine lymphoma treatment options have been identified, including the exact stage and specific type of lymphoma. Chemotherapy has become the main method for treating both HL and NHL. Meanwhile, other therapies, such as radiation, immunotherapy, have also been combined with chemotherapy to improve therapeutic efficacy. Furthermore, recent studies have revealed that immunotherapy should be a powerful tool for activating the immune system against lymphomas. For instance, several antibody-drug conjugates designed to deliver drugs to tumors, including brentuximab vedotin and ibritumomab, have been approved for the treatment of NHL patients. Besides, therapeutic monoclonal antibodies, such as rituximab and obinutuzumab, have been considered as first-line therapy for NHL.
Fig.1 Pathways Viruses May Exploit to Specifically Target Malignant Cells. (Alain, 2003)
Oncolytic Viral Therapy for Lymphoma
Oncolytic viruses are a group of viruses that contain RNA genome or DNA genome. Oncolytic viruses can be modified to acquire the abilities of infection, replication, and killing cancer cells without harming normal cells in humans. Meanwhile, many reports have illustrated that oncolytic viruses trigger a range of immunogenic processes to further activate specific antitumor immune reactions. As a result, oncolytic viruses have been considered as new therapeutic agents against both liquid and solid tumors. Many preclinical studies have indicated that various oncolytic viruses, including adenovirus, reovirus, and measles virus, play an important role in inhibiting and destroying B- and T-lymphoma-derived cells in different animal models. For example, an attenuated measles virus has been designed to infect different types of lymphoid cells. The data have suggested that it can cause apoptotic cell death and might be a useful method for the treatment of lymphoma.
Clinical Trials for Lymphoma Treatment
Due to the success of oncolytic viruses in preclinical studies, many clinical trials have been conducted on HL and NHL patients. Currently, several oncolytic viruses, such as reovirus and measles virus, are among the high-grade lymphoma therapeutic studies. For instance, a randomized phase I study has been designed to evaluate the efficacy and safety of the adenovirus ONYX015, a recombinant virus, in patients with diffuse large B-cell lymphoma (DLBCL). Furthermore, novel immunotherapy in NHL has been developed recently by combining antibodies with oncolytic viruses. In general, the double-blind randomized clinical trial is commonly used for evaluating the safety and potential efficacy of these combination viral therapies in patients with lymphomas. The disease response rates and survival rates will be analyzed to evaluate the effectiveness of oncolytic viral therapy. Besides, the oncolytic properties of the virus against different kinds of lymphomas should need to be identified.
Reference
- Alain, T.; et al. Lymphomas and Oncolytic Virus Therapy. Clin Lymphoma. 2003, 4(2): 104-11.