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In this review, we discuss the landmark data that led to the commercialization of four novel FDA-approved T-cell\u2013based therapeutics in solid malignancies, including tarlatamab for small cell lung cancer, afamitresgene autoleucel for synovial sarcoma, lifileucel for metastatic melanoma, and tebentafusp for metastatic uveal melanoma. We discuss the targetable antigen landscape of CAR-T therapies and BiTEs under investigation in solid malignancies. We explore the translational potential for various CARs under active investigation, including human epidermal growth factor receptor 2\u2013directed CARs in breast cancer, prostate stem cell antigen\u2013directed CARs for prostate cancer, epidermal growth factor receptor (EGFR)-IL13Ra2 and EGFR-vIII CARs for glioblastoma, and GD2-directed CARs for neuroblastoma. We glean from lessons learned for existing CAR-T therapies and BiTEs for hematologic malignancies and emphasize solutions toward facilitating the clinical rollout of T-cell\u2013based therapies in solid tumors, including scalability to meet the growing needs of clinical oncology. Some solutions include addressing on-target, off-tumor toxicity; improving the manufacturing of CARs; optimizing the tissue-specific tumor microenvironment by combating immune desert tumors; and discovering natural tumor neoantigens and non\u2013self-epitopes generated by tumor-specific mutations. These concepts can help provide transformative benefits for patients with solid malignancies in the coming years.<\/jats:p>","DOI":"10.1200\/po-24-00753","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T20:02:54Z","timestamp":1743019374000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":17,"title":["Expanding the Therapeutic Reach of Chimeric Antigen Receptor T-Cells and Bispecific T-Cell Engagers Across Solid Tumors"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8103-0376","authenticated-orcid":true,"given":"William K.","family":"Gerber","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Hematology\/Oncology, UMass Memorial Medical Center, UMass Chan Medical School, Worcester, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8434-9474","authenticated-orcid":true,"given":"Yiyu","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology\/Oncology, UMass Memorial Medical Center, UMass Chan Medical School, Worcester, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8208-1902","authenticated-orcid":true,"given":"Shyam A.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology\/Oncology, UMass Memorial Medical Center, UMass Chan Medical School, Worcester, MA"},{"name":"Center for Clinical and Translational Science, UMass Chan Medical School, Worcester, MA"},{"name":"Cancer Biology Program, Morningside Graduate School of Biomedical Sciences, UMass Chan Medical School, Worcester, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"crossref","first-page":"7028","DOI":"10.4049\/jimmunol.180.10.7028","article-title":"Antigen sensitivity of CD22-specific chimeric TCR is modulated by target epitope distance from the cell membrane","volume":"180","author":"James SE","year":"2008","unstructured":"James SE, Greenberg PD, Jensen MC, et al: Antigen sensitivity of CD22-specific chimeric TCR is modulated by target epitope distance from the cell membrane. 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