Researchers from Seattle Childen’s Research Institute have shown that engineered human plasma B cells (ePCs) can effectively treat leukemia in a humanized animal model. This milestone achievement opens up new possibilities for treating cancer, autoimmune disorders, and protein deficiency diseases.
The study, published in Molecular Therapy, focused on developing ePCs that produce bispecific antibodies to target B-cell acute lymphoblastic leukemia (B-ALL). These engineered cells offer a potential solution to the limitations of current treatments like blinatumomab, which require continuous high-dose intravenous infusions.
Senior author Richard James explains, "We hope that this proof-of-concept study is the first of many applications of engineered plasma B cells, and eventually will lead to a single-shot therapeutic." The longevity of these cells, potentially exceeding 10 years, makes them an attractive option for long-term drug delivery.
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The researchers successfully created ePCs capable of secreting anti-CD19 bispecific antibodies, which demonstrated antitumor activity in immunodeficient mice with acute lymphoblastic leukemia patient-derived xenografts. Remarkably, the concentration of bispecifics in serum one month after cell delivery was comparable to levels observed in patients receiving continuous blinatumomab infusion.
"We created engineered plasma B cells capable of continuously producing bispecific antibodies throughout the treatment period after only one injection," James notes. "These cells effectively eliminated tumors to a comparable extent as the clinical drug."
While the results are promising, the researchers acknowledge potential challenges, including toxicity risks and the need for further studies in humanized mice and non-human primates. James adds, "In the short term, we plan to test whether engineered plasma B cells that produce bispecific antibodies are effective in other B cell-mediated diseases, including autoimmunity."