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T cell engagers (TCEs) are targeted immunotherapies that have emerged as a promising treatment to redirect effector T cells for tumor cell killing. The strong therapeutic value of TCEs, established by the approval of blinatumomab for the treatment of B cell precursor acute lymphoblastic leukemia, has expanded to include other hematologic malignancies, as well as some solid tumors. Successful clinical development of TCEs in solid tumors has proven challenging, as it requires additional considerations such as the selectivity of target expression, tumor accessibility, and the impact of the immunosuppressive tumor microenvironment. In this review, we provide a brief history of blinatumomab, summarize learnings from TCEs in hematologic malignancies, and highlight results from recent TCE trials in solid tumors. Additionally, we examine approaches to improve the efficacy and safety of TCEs in solid tumors, including therapeutic combinations to increase the depth and durability of response.
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