Ofatumumab and Granzyme B as immunotoxin against CD20 antigen

Sefid, Fatemeh; Bahrami, Armina Alagheband; Payandeh, Zahra; Khalili, Saeed; Azamirad, Ghasem; Kalantar, Seyed Mehdy; Touhidinia, Maryam

doi:10.1007/s40203-022-00120-6

Cited by 1 publication

(1 citation statement)

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“…To the best of our knowledge, immunotoxins of obinutuzumab or other anti-CD20 antibodies such as ofatumumab, tositumomab, and ibritumomab conjugated to RIPs are not yet described. Only an in-silico study of an immunotoxin composed of ofatumumab and the apoptosis inducing enzyme granzyme B is available [ 44 ].…”

Section: Introductionmentioning

confidence: 99%

Improved Therapy of B-Cell Non-Hodgkin Lymphoma by Obinutuzumab-Dianthin Conjugates in Combination with the Endosomal Escape Enhancer SO1861

Panjideh

Niesler

Weng

et al. 2022

Toxins

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Immunotoxins do not only bind to cancer-specific receptors to mediate the elimination of tumor cells through the innate immune system, but also increase target cytotoxicity by the intrinsic toxin activity. The plant glycoside SO1861 was previously reported to enhance the endolysosomal escape of antibody-toxin conjugates in non-hematopoietic cells, thus increasing their cytotoxicity manifold. Here we tested this technology for the first time in a lymphoma in vivo model. First, the therapeutic CD20 antibody obinutuzumab was chemically conjugated to the ribosome-inactivating protein dianthin. The cytotoxicity of obinutuzumab-dianthin (ObiDi) was evaluated on human B-lymphocyte Burkitt’s lymphoma Raji cells and compared to human T-cell leukemia off-target Jurkat cells. When tested in combination with SO1861, the cytotoxicity for target cells was 131-fold greater than for off-target cells. In vivo imaging in a xenograft model of B-cell lymphoma in mice revealed that ObiDi/SO1861 efficiently prevents tumor growth (51.4% response rate) compared to the monotherapy with ObiDi (25.9%) and non-conjugated obinutuzumab (20.7%). The reduction of tumor volume and overall survival was also improved. Taken together, our results substantially contribute to the development of a combination therapy with SO1861 as a platform technology to enhance the efficacy of therapeutic antibody-toxin conjugates in lymphoma and leukemia.

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Section: Introductionmentioning

confidence: 99%