ADC Development for Lymphoma

Lymphoma is the most common hematologic malignancy. Despite the relative success of chemotherapy and radiotherapy for this kind of disease, some patients are either resistant to first-line therapy or relapse after initial treatment. Therefore, novel therapeutic methods are needed for refractory or relapsed patients. Antibody-drug conjugates (ADCs) present promising in lymphoma treatment because it can selectively bind and effectively deliver cytotoxic drugs to tumor cells with significantly decreased systemic toxicity. As an expert in the ADC development field, Creative Biolabs provides comprehensive ADC design and development services for lymphoma drug discovery.

Introduction of Lymphoma

Lymphoma is a blood cancer arising from lymphocytes. These cells exist in all kinds of organs or tissues such as the lymph nodes, bone marrow, thymus, spleen. Lymphocytes often show abnormal change and growth during the lymphoma process. Lymphomas have dozens of subtypes, such as the anaplastic large cell lymphoma (ALCL), the Hodgkin's lymphomas (HL), the non-Hodgkin lymphomas (NHL) and diffuse large B-cell lymphoma (DLBCL). The two primary categories of lymphomas are HL and NHL, and about 90% of lymphomas are NHL. Lymphomas and leukemias are a part of the extensive group of tumors of the hematopoietic and lymphoid tissues. In most cases, the cause of the cancer is unclear. However, some possible factors associated with this disease include age, genders, having a weak immune system, having an immune system disease, having been infected by a virus, exposed to chemicals and treated for cancer with radiation. Signs and symptoms generally include enlarged lymph nodes, fever, drenching sweats, unintended weight loss, itching, as well as constantly feeling tired and sweating at night. To date, the main treatment approaches of these diseases include chemotherapy, radiation therapy, targeted therapy, and surgery.

Lymphoma Fig.1 Lymphoma.

Current Therapeutic Strategies for Lymphoma

Currently, a variety of new agents are being evaluated in preclinical and clinical settings for the treatment of lymphoma, but the failure rate of drug development processes remains very high owing to unacceptable toxicities and/or a lack of antitumour efficacy. Fortunately, biomarkers confer the selection to a specific targeted therapy to improve the success of drug development.

In recent years, several therapeutic strategies have been developed successfully to improve the treatment of lymphoma and received regulatory approval. These agents include the ADCs (brentuximab vedotin), novel glycol-engineered anti-CD20 antibody obinutuzumab, B-cell receptor signaling inhibitor ibrutinib, PI3K-δ inhibitor idelalisib, and the immunomodulatory drug lenalidomide. Besides, various investigated targeted drugs have also demonstrated potential efficacy, including the BCL2 inhibitor venetoclax, the second-generation inhibitor of Bruton tyrosine kinase (BTK) acalabrutinib and several ADCs. In addition, many immunotherapies have also shown significant efficacy in the lymphoma treatment, such as mono-specific and bi-specific antibodies, immune-checkpoint inhibitors, and engineered chimeric antigen receptor (CAR) T cells.

Brentuximab vedotin mechanism of action. Fig.2 Brentuximab vedotin mechanism of action. (Palanca-Wessels, 2015)

What Can We Do for You?

ADCs aim to take advantage of the specificity of monoclonal antibodies to deliver potent cytotoxic drugs selectively to antigen-expressing tumour cells. This innovative therapy method is presenting its potential in the treatment of lymphoma and has led to some successful results into clinical use, such as the FDA approved brentuximab vedotin, the first agent in this class to be approved for the treatment of HL and DLBCL. Here at Creative Biolabs, we are dedicated to helping clients design and develop an effective ADC for the therapy of lymphoma. Our ADC development services target lymphoma including:

As one of the most professional service providers in the ADC field, Creative Biolabs offers customized ADCs design and construction services to help promote your projects. We also provide a variety of ADC-related products such as the linkers and Drug-linker Complexes to meet the specific demand of every client. Please contact us for more information.

Reference

  1. Palanca-Wessels, M.C.A.; et al. Safety and activity of the anti-CD79B antibody-drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study. The Lancet Oncology. 2015, 16(6): 704-715.


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