T cell bispecific antibodies (TCBs) are an emerging class of immunotherapeutics with several TCBs approved by the FDA for the treatment of leukemias, lymphomas, and myelomas. TCBs label tumor cells with one of their ends, and attract immune cells with another end to coerce them into tumor cell killing. However, one major challenge in the development of TCBs are 'on-target, off-tumor' toxicities at sites in the body that also express TCB-targeted antigens. Scientists have now created an immune-infiltrated human kidney organoid-on-chip model that allows kidney toxicity of TCBs.
A growing repertoire of cell and molecule-based immunotherapies is offering patients with indomitable cancers new hope by mobilizing their immune systems against tumor cells. An emerging class of such immunotherapeutics, known as T cell bispecific antibodies , are of growing importance with several TCBs that the U.S. Food and Drug Administration approved for the treatment of leukemias, lymphomas, and myelomas.
Now, a new cross-disciplinary, cross-organizational study created an immune-infiltrated kidney tissue model for investigating on-target, off-tumor effects of TCBs and potentially other immunotherapy drugs. The team of bioengineers and immune-oncologists who performed the study at the Wyss Institute for Biologically Inspired Engineering at Harvard University, Harvard John A.
"Importantly, our central finding was that the WT1-TCB tool compound resulted in the selective killing of WT-1-expressing podocytes in the kidney organoids, while it did not affect cells in the distal and proximal tubules. This compellingly demonstrates that our engineered humankidney organoid-on-chip system has utility as a preclinical drug development tool for assessing on-target, off-tumor toxicities of TCBs as a new class of immunotherapeutics," explained Katharina Kroll, Ph.D.
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