Bispecific T-cell engagers beyond hematology: Expanding uses in solid tumors

ObjectiveTo review the mechanism of action, clinical efficacy, safety considerations and future development of bispecific T-cell engagers (BTCEs) in solid tumors.Data sourcesA literature search was conducted using PubMed for clinical trials leading to FDA approvals and major oncology conference proceedings through February 2026. Major ongoing clinical trials were identified through a search of clinicaltrials.gov. Search terms included "bispecific T-cell engager," "BiTE," "solid tumors," "tarlatamab," and "tebentafusp." Prescribing information was also evaluated.Data summaryBTCEs are antibodies designed to redirect cytotoxic T-cells toward tumor cells through binding of CD3 and tumor-associated antigens. FDA approvals of tebentafusp for HLA-A*02:01-positive metastatic uveal melanoma and tarlatamab for extensive stage small cell lung cancer have established utility of BTCE therapy in solid malignancies, with improved outcomes over conventional chemotherapy and immunotherapy. BTCEs have unique toxicities, such as cytokine release syndrome, that must be monitored and treated appropriately. Ongoing investigations are evaluating novel targets, optimized molecular constructs to overcome development challenges, including toxicity and tumor microenvironment barriers, as well as combination treatment strategies to improve the efficacy of BTCEs in solid tumors.ConclusionsTebentafusp and tarlatamab have established proof of concept for BTCE therapy in solid tumors, bridging the gap from hematologic malignancies. This class of therapy represents a promising platform for expanding applications across tumor types. Continued advances in target selection and strategies to overcome the tumor microenvironment and T-cell evasion barriers are expected to further expand the role of BTCEs in solid tumors.