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EHA 2026 | The rationale behind exploring the dual-antigen-targeting CAR T-cell construct ADZ0120 in myeloma
In this interview, Binod Dhakal, MD, Medical College of Wisconsin, Milwaukee, WI, discusses the rationale and benefits of targeting both BCMA and CD19 in multiple myeloma (MM) with the dual-antigen-targeting CAR T-cell construct AZD0120. Dr Dhakal highlights that this approach could enhance the durability of CAR-T responses and reduce manufacturing time. This interview took place at the 31st Congress of the European Hematology Association (EHA) in Stockholm, Sweden.
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Transcript
So, AZD0120, which is a dual targeting BCMA and CD19, has two unique aspects. Number one, it offers an advantage by targeting both the malignant plasma cells by BCMA and CD19, which is supposed to present in myeloma progenitors. CD19 is a validated target in B-cell malignancies including lymphoma. In myeloma, relapsed multiple myeloma cells can express low levels of CD19...
So, AZD0120, which is a dual targeting BCMA and CD19, has two unique aspects. Number one, it offers an advantage by targeting both the malignant plasma cells by BCMA and CD19, which is supposed to present in myeloma progenitors. CD19 is a validated target in B-cell malignancies including lymphoma. In myeloma, relapsed multiple myeloma cells can express low levels of CD19. At the same time, the progenitor cells can also present with CD19. So targeting both the myeloma cells via BCMA and CD19 offers an advantage that could contribute to longer durability of responses. In addition, AZD0120 is manufactured with the next-generation rapid manufacturing process. The current manufacturing process with the long turnaround time, limited patient access, and reduced T-cell fitness can be overcome by this next-generation manufacturing because the next-generation manufacturing process can offer an advantage of healthier, more naive T-cells. If you look at the current CAR-T manufacturing, about 30% of the final cell product of the approved CAR-T therapies have a naive phenotype, both stem cell memory and central memory phenotype. In AZD0120, with rapid manufacturing, we are seeing 70% of these cells are stem cell and central memory T cells. That has been shown to, you know, be very powerful cells for anti-tumor activity. So with the strategy of rapid manufacturing and healthy T-cells as well as dual targeting, we believe that this can overcome and can be very effective in most patients, and also prevent the ongoing relapses that we’re seeing in the current CAR-T.
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