Two reports from the research teams of Niels van de Donk, Sonja Zweegman and Tuna Mutis show promising results in laboratory studies with two different antibodies that target multiple myeloma cells.
The teams are working with a special kind of therapeutic antibodies, called bispecific antibodies, which can bind to two targets at the same time: in this case, proteins that are highly expressed on the surface of multiple myeloma cancer cells (BCMA and GPRC5D), and T-cells, a type of immune cell. The bispecific antibodies help to recruit T-cells to the cancerous cell which results in its destruction by the T-cell. Lower amounts of T-cells resulted in reduced activity of the antibodies. These two promising novel antimyeloma agents (teclistamab and talquetamab) are now being tested in patients without other available treatment options in clinical trials. The first results from these studies show that high response rates can be achieved with these agents in heavily pretreated patients, with a manageable toxicity profile. Updated results obtained with these bispecific antibodies will be presented at the European Haematology Association (EHA) conference and at ASCO.
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Verkleij, C.P.M., et al. (2021) Preclinical activity and determinants of response of the GPRC5DxCD3 bispecific antibody talquetamab in multiple myeloma. Blood Adv 5: 2196–2215.Frerichs, K.A., et al (2020) Preclinical activity of JNJ-7957, a novel BCMA×CD3 bispecific antibody for the treatment of multiple myeloma, is potentiated by daratumumab. Clin Cancer Res 26: 2203-2215.Niels W.C.J. van de Donk et al, Teclistamab, a b-cell maturation antigen (bcma) × cd3 bispecific antibody, in patients with relapsed/refractory multiple myeloma: updated phase 1 results. EHA Library. 06/09/21; 324601; S193 .Amrita Y. Krishnan et al, Talquetamab, a g protein-coupled receptor family c group 5 member d (gprc5d) × CD3 bispecific antibody, in relapsed/refractory multiple myeloma: updated results of a phase 1, first-in-human study. EHA library. 06/09/21; 324599; s191.