Four Monoclonal Antibodies for Treatment of Non-Hodgkin's Lymphoma

Posted by Candy Swift on February 11th, 2020

Lymphoma is a tumor that develops on lymphocytes, divided into Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL) according to pathological. Most non-Hodgkin's lymphomas belong to B-cell lymphomas. It’s reported that 43 million people have developed non-Hodgkin's lymphoma in 2015, resulting in 23,1400 deaths, and around 2.1% Americans have had non-Hodgkin's lymphoma in their lifetime. The common symptoms of NHL include enlarged lymph nodes, fever, night sweats, light weight loss, and tiredness.

Treatment for non-Hodgkin's lymphoma depends on how quickly the lymphoma develops and whether the lymphoma appears in one or more places. At present, treatment methods of NHL include chemotherapy, radiation therapy, immunotherapy, targeted therapy, bone marrow transplantation, and surgery. However, radiation therapy and some chemotherapy treatments may increase the risk of other cancers, heart disease or neurological problems in the coming decades. On the contrary, immunotherapy, mainly using monoclonal antibody, focuses on trigger a more powerful immune response with less side-effect compared to traditional therapy.

1. Rituximab 

Rituximab is the first monoclonal antibody approved in the world for the treatment of non-Hodgkin's lymphoma, pioneering the targeted treatment of lymphoma. Prior to the advent of rituximab, traditional chemotherapy drugs have been the first-line treatment options for lymphoma. Now, the combination of rituximab and chemotherapy drugs CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and CVP (cyclophosphamide, vincristine, prednisone) has become the standard treatment regime for large B-cell lymphoma and follicular lymphoma.

2. Ibritumomab Tiuxetan

As the world's first radiolabeled monoclonal antibody used for the treatment of refractory B-cell non-Hodgkin's lymphoma, Ibritumomab Tiuxetan is an anti-CD20 monoclonal antibody labeled with the radionuclide indium 111 (In-111) or yttrium 90 (Y-90). After the anti-CD20 monoclonal antibody carrying the radionuclides is injected into the patient, the monoclonal antibody will bind to mature B cells and B cell tumor cells expressing CD20, and the radionuclides carried by them will release radiation to kill these tumor cells.

3. Tositumomab

Tositumomab is another antibody drug labeled with a radioactive element, similar to Ibritumomab Tiuxetan, for the treatment of relapsed or refractory follicles or deformed non-Hodgkin lymphoma.

4. Mogamulizumab

Among the many types of non-Hodgkin's lymphoma, there is a subtype called cutaneous T-cell lymphoma, which contains mycosis fugoides (MF) or Sezary syndrome (SS). Mogamulizumab is a humanized CC chemokine receptor 4 (CCR4) monoclonal antibody, which has passed the FDA's breakthrough therapy designation and priority review, to treat adult patients with relapsed or refractory MF or SS who have received at least one systemic therapy. CCR4, overexpressed on peripheral T cell leukemia/lymphoma cells, is a specific drug target. Therefore, drugs developed with CCR4 as a target can achieve the treatment of immune diseases and solid tumors by blocking CCR4 expressed on regulatory T cells, and can target over-expression on peripheral T-cell leukemia / lymphoma cells.

Unlike traditional radiotherapy and chemotherapy, which directly kill tumor cells, immune targeted therapy mainly treats tumors by strengthening the function of tumor-specific T lymphocytes. More efficient and low-toxic immunotherapy is expected for NHL treatment in the future. The combination of immune-targeted drugs and traditional cytotoxic drugs, as well as the combination of various immune-targeted drugs are also essential research directions.