{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:14:05Z","timestamp":1787505245934,"version":"build-2736575974"},"reference-count":50,"publisher":"Innovative Healthcare Institute","issue":"3","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    A rapidly advancing class of engineered immunoglobulins, known as bispecific antibodies (bsAbs), that bind two distinct antigens offers new approaches for tumor targeting and immune modulation. BsAbs function as immune cell engagers, immune checkpoint modulators, or signaling pathway inhibitors. They differ in half-life, stability, and tissue penetration depending on whether they exist in crystallizable fragment (Fc)\u2013based or fragment-based formats. Although bsAbs have shown strong efficacy in hematologic malignancies, their translation to solid tumors has been limited by antigen heterogeneity, off-tumor toxicity, and the immunosuppressive tumor microenvironment. Recent clinical advancements have led to eight approved bsAbs for solid tumors, including amivantamab for\n                    <jats:italic>EGFR<\/jats:italic>\n                    (epidermal growth factor receptor) exon 20 insertion\u2013mutated non-small cell lung cancer (NSCLC), tebentafusp for uveal melanoma, cadonilimab for cervical cancer, tarlatamab for small cell lung cancer, ivonescimab for PD-L1 (programmed death\u2013ligand 1)\u2013positive NSCLC, zanidatamab for HER2 (human epidermal growth factor receptor 2)\u2013amplified biliary tract cancer, zenocutuzumab for\n                    <jats:italic>NRG1<\/jats:italic>\n                    (neuregulin 1) fusion\u2013positive tumors, and catumaxomab for malignant ascites. These agents have demonstrated durable clinical benefit with manageable safety profiles. However, class-related toxicities such as cytokine release syndrome, immune effector cell\u2013associated neurotoxicity syndrome, and on-target off-tumor effects remain important challenges. Advances in Fc silencing, affinity tuning, and tumor-restricted activation have improved therapeutic selectivity and tolerability. Ongoing innovations include bsAb-drug conjugates, proteolysis-targeting chimeras (PROTACs), and multispecific antibody platforms designed to reprogram the tumor microenvironment and enhance immune infiltration. Biomarker-driven patient selection and rational combination strategies are expected to further improve outcomes. As engineering technologies mature, bsAbs are expected to become integral to precision oncology, expanding safe and effective immunotherapy options for patients with solid tumors. This review aims to provide a comprehensive overview of the mechanisms, clinical applications, challenges, and future directions of bsAbs in solid tumors.\n                  <\/jats:p>","DOI":"10.36401\/jipo-25-36","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T12:26:36Z","timestamp":1783427196000},"page":"88-99","source":"Crossref","is-referenced-by-count":1,"title":["Bispecific Antibodies in Solid Tumors: Mechanistic Insights, Clinical Advances, and Future Directions"],"prefix":"10.36401","volume":"9","author":[{"given":"Radiya","family":"Almosa","sequence":"first","affiliation":[{"name":"Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan Macalalad","family":"Mendoza","sequence":"additional","affiliation":[{"name":"Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tin-Yun","family":"Tang","sequence":"additional","affiliation":[{"name":"Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1653-2012","authenticated-orcid":true,"given":"Bettzy","family":"Stephen","sequence":"additional","affiliation":[{"name":"Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"22027","reference":[{"key":"i2590-017X-9-3-88-b01","series-title":"BMC Cancer","first-page":"33","article-title":"Cancer incidence in immunocompromised patients: a single-center cohort study","volume":"23","author":"Ilham","year":"2023","unstructured":"Ilham S,\nWillis C,\nKim K, et al. 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Nat Commun. 2019;10:5387."},{"issue":"suppl 2","key":"i2590-017X-9-3-88-b46","series-title":"J ImmunoTher Cancer","first-page":"A1374","article-title":"1325: Preclinical activity and safety profile of JANX007, a novel PSMA-targeting tumor-activated T cell engager for treatment of metastatic castration-resistant prostate cancer","volume":"10","author":"DiRaimondo","year":"2022","unstructured":"DiRaimondo T,\nBudimir N,\nShenhav S, et al. 1325: Preclinical activity and safety profile of JANX007, a novel PSMA-targeting tumor-activated T cell engager for treatment of metastatic castration-resistant prostate cancer. J ImmunoTher Cancer. 2022;10(suppl 2):A1374."},{"key":"i2590-017X-9-3-88-b47","series-title":"Onco Targets Ther","first-page":"545","article-title":"Nephrotoxicity in bispecific antibodies recipients: focus on T-cell-engaging bispecific antibodies","volume":"17","author":"Wen","year":"2024","unstructured":"Wen X,\nXu G. Nephrotoxicity in bispecific antibodies recipients: focus on T-cell-engaging bispecific antibodies. Onco Targets Ther. 2024;17:545\u2013556."},{"key":"i2590-017X-9-3-88-b48","series-title":"Eur J Cancer","first-page":"114075","article-title":"Reactions and adverse events induced by T-cell engagers as anti-cancer immunotherapies, a comprehensive review","volume":"205","author":"G\u00e9raud","year":"2024","unstructured":"G\u00e9raud A,\nHueso T,\nLaparra A, et al. Reactions and adverse events induced by T-cell engagers as anti-cancer immunotherapies, a comprehensive review. Eur J Cancer. 2024;205:114075."},{"key":"i2590-017X-9-3-88-b49","series-title":"Curr Hematol Malig Rep","first-page":"237","article-title":"Management of toxicities associated with BCMA, GPRC5D, and FcRH5-targeting bispecific antibodies in multiple myeloma","volume":"19","author":"Pan","year":"2024","unstructured":"Pan D,\nRichter J. 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