ADC Development for DLBCL

Diffuse large B-cell lymphoma (DLBCL) is one of the most common types of lymphoma in the worldwide, conventional treatment only be fit for young patients, and long-term survival is rare. New therapeutic strategies are required for refractory or relapsed patients due to limited treatment options with unsatisfying results. Antibody-drug conjugates (ADCs) are showing promise in the cancer treatment that can increase the efficacy and decrease the toxicity in comparison with traditional cytotoxic drugs. Empowered by advanced technology platforms and experienced technical personnel, Creative Biolabs is fully competent and dedicated to providing your one-stop ADC development service for DLBCL therapy.

Introduction of DLBCL

DLBCL is the most frequent form of the aggressive non-Hodgkin lymphoma, accounting for approximately 30-58% of cases. The majority of cases of DLBCL occur in de novo, while some develop from indolent lymphoma. DLBCL can be subclassified as germinal center B-cell-like (GCB) or activated B-cell-like (ABC) subtypes based on gene expression profiling. Generally, the ABC subtype shows a worse prognosis than the GCB subtype. The symptoms of DLBCL are often characterized by fever, drenching night sweats, weight loss, belly or chest pain or pressure, shortness of breath or cough and itching. DLBCL has been found in all age groups except for the very young. To date, the etiology of this lymphoma is unknown for most patients. Some risk factors include immunosuppression (such as the AIDS or autoimmune diseases), ultraviolet radiation, pesticides, hair dyes, and diet. A subset of DLBCL disease is highly associated with the EBV virus.

 An illustration of putative oncogene dependencies in DLBCL. Fig.1 An illustration of putative oncogene dependencies in DLBCL. (Steinhardt, 2012)

ADC Development for DLBCL

Coltuximab ravtansine (SAR3419) is a novel ADC composed of an anti-CD19 monoclonal antibody conjugated to a potent cytotoxic maytansinoid, DM4, via disulfide bond linker. The antibody specifically binds to the CD19 antigen of B cells, resulting in internalization of the receptor-drug complex and intracellular release of DM4. DM4 is a potent inhibitor of tubulin polymerization and microtubule assembly, which can achieve the killing of cancer cells. This ADC has been used in the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma in phase II study. Clinical studies showed that SAR3419 was well tolerated and resulted in moderate clinical responses in pretreated patients with relapsed/refractory DLBCL.

IMGN529 is another antibody-drug conjugate consisting of a CD37-targeting antibody conjugated to the maytansine-derived microtubule disruptor, DM1. This ADC has shown promising preclinical and clinical activity in DLBCL. Studies revealed that the combination of IMGN529 and rituximab presented more potent antitumor activity than either agent alone in patients with relapsed and/or refractory DLBCL, which was associated with increased apoptotic induction and cell death.

 Duration of response by individual patient during the SAR3419 treatment. Fig.2 Duration of response by individual patient during the SAR3419 treatment. (Trnĕný, 2018)

What Can We Do for You?

ADCs can selectively deliver cytotoxic drugs to cancer cells to increase the percentage of drug molecules, thus lowering the minimum effective dose and increasing the maximum tolerated dose. For the DLBCL treatment, ADCs could be a potential therapeutic strategy, which have been under actively investigated. At present, Creative Biolabs provides customized ADC design and development services for the DLBCL disease. Our high-quality products and services will promote the progress of your ADC development projects. Please contact us for more information and a detailed quote.

Targets of Creative Biolabs’s ADCs development services against DLBCL:

CD19      CD37

References

  1. Steinhardt, J. J.; et al. Promising personalized therapeutic options for diffuse large B-cell lymphoma subtypes with oncogene addictions. Clinical Cancer Research. 2012, 18(17): 4538-4548.
  2. Trnĕný, M.; et al. A phase II multicenter study of the anti-CD19 antibody drug conjugate coltuximab ravtansine (SAR3419) in patients with relapsed or refractory diffuse large B-cell lymphoma previously treated with rituximab-based immunotherapy. Haematologica. 2018, 103(8): 1351-1358.


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