{"id":598575,"date":"2026-09-13T00:28:09","date_gmt":"2026-09-13T00:28:09","guid":{"rendered":"https:\/\/www.newsbeep.com\/nz\/598575\/"},"modified":"2026-09-13T00:28:09","modified_gmt":"2026-09-13T00:28:09","slug":"t-cell-engagers-in-small-cell-lung-cancer","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/nz\/598575\/","title":{"rendered":"T-cell engagers in small cell lung cancer"},"content":{"rendered":"

Review<\/p>\n

. 2026 Sep 15;132(18):e70600.<\/p>\n

doi: 10.1002\/cncr.70600.<\/p>\n

Affiliations<\/p>\n

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Affiliation<\/p>\n

1 Dana-Farber Cancer Institute, Boston, MA, USA.<\/p>\n

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Review<\/p>\n

Alissa J Cooper\u00a0et al.<\/p>\n

Cancer.<\/p>\n

2026.<\/p>\n

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Abstract<\/p>\n

PubMed<\/p>\n

PMID<\/p>\n

. 2026 Sep 15;132(18):e70600.<\/p>\n

doi: 10.1002\/cncr.70600.<\/p>\n

Affiliation<\/p>\n

1 Dana-Farber Cancer Institute, Boston, MA, USA.<\/p>\n

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Abstract<\/p>\n

The management of small cell lung cancer (SCLC) has been transformed by the advent of effective T-cell engagers (TCEs), which circumvent the traditionally immunosuppressive tumor microenvironment by directly facilitating T-cell-mediated cell lysis. Delta-like ligand 3 (DLL3) has emerged as the predominant target for TCE development in SCLC given its high expression on tumor cells and relatively spared expression on normal tissues. Tarlatamab, a DLL3xCD3 TCE that is now an approved agent for SCLC, has revolutionized outcomes for patients with SCLC, but raises challenges in terms of toxicity management and real-world implementation. In this review, we discuss the current landscape and future directions of DLL3-targeting TCE in SCLC, including accumulating real-world clinical experience, nascent investigation into patient selection and modifiers of response and resistance, and anticipated paradigm shifts as a result of ongoing clinical trials.\n <\/p>\n

Keywords:<\/p>\n

biomarkers; cytokines; immunotherapy; patient selection; small cell lung carcinoma.\n <\/p>\n

\n \u00a9 2026 American Cancer Society. All rights reserved, including rights for text and data mining and training of artificial intelligence technologies or similar technologies.\n <\/p>\n

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Conflict of interest statement<\/p>\n

A.J.C. has received honoraria from MJH Life Sciences, Ideology Health, Intellisphere LLC, MedStar Health, PeerDirect, PER, and CancerGRACE, and consulting fees from AbbVie, Amgen, AstraZeneca, BI, Daiichi, Gilead Sciences, Novartis, and Regeneron. She reports prior research funding to institution from Merck, Monte Rosa, AbbVie, Roche, Daiichi Sankyo, and Amgen (ended 8\/2025). J.S. has received consulting fees from Abbvie, Amgen, Astra Zeneca, Boehringer Ingelheim, Daiichi\u2010Sankyo, Fosun, Genentech, Gilead, GSK, Jazz Pharmaceuticals, Lilly, Merck, Novartis, Pfizer, Pharma Mar, and Sanofi and research funding from Amgen and Novartis.<\/p>\n

Figures<\/p>\n


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FIGURE 1 <\/p>\n

(A) Illustration of various T\u2010cell\u2026 <\/p>\n

FIGURE 1 <\/p>\n

(A) Illustration of various T\u2010cell engager structures and targets. (B) Diagram of mechanism\u2026 <\/p>\n

FIGURE 1<\/p>\n

(A) Illustration of various T\u2010cell engager structures and targets. (B)\u00a0Diagram of mechanism of action of cytotoxicity of DLL3\u2010targeting T\u2010cell engagers.<\/p>\n


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FIGURE 2 <\/p>\n

(A) Pretreatment scans of liver\u2026 <\/p>\n

FIGURE 2 <\/p>\n

(A) Pretreatment scans of liver and brain. (B) Scans of liver and brain\u2026 <\/p>\n

FIGURE 2<\/p>\n

(A) Pretreatment scans of liver and brain. (B)\u00a0Scans of liver and brain 6 weeks after treatment initiation. (C)\u00a0Pretreatment scans of lung and liver. (D)\u00a0Scans of lung and liver after three doses of therapy.<\/p>\n

References<\/p>\n

Mahadevan NR, Knelson EH, Wolff JO, et al. Intrinsic immunogenicity of small cell lung carcinoma revealed by its cellular plasticity. Cancer Discov. 2021;11(8):1952\u20101969. doi: 10.1158\/2159-8290.cd-20-0913<\/p>\n

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Doyle A, Martin WJ, Funa K, et al. Markedly decreased expression of class I histocompatibility antigens, protein, and mRNA in human small\u2010cell lung cancer. J Exp Med. 1985;161(5):1135\u20101151. doi: 10.1084\/jem.161.5.1135<\/p>\n

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Yazawa T, Kamma H, Fujiwara M, et al. Lack of class II transactivator causes severe deficiency of HLA\u2010DR expression in small cell lung cancer. J Pathol. 1999;187(2):191\u2010199. doi: 10.1002\/(sici)1096-9896(199901)187:2<191::aid-path206>3.0.co<\/a>;2-3<\/p>\n

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Kellish P, Shabashvili D, Rahman MM, et al. Oncolytic virotherapy for small\u2010cell lung cancer induces immune infiltration and prolongs survival. J Clin Investig. 2019;129(6):2279\u20102292. doi: 10.1172\/jci121323<\/p>\n

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Baeuerle PA, Sauer K, Grieshaber\u2010Bouyer R, Michaelson J. T cell engagers emerge as a compelling therapeutic modality. J Exp Med. 2026;223(2):e20251652. doi: 10.1084\/jem.20251652<\/p>\n

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Show all 69 references<\/p>\n

MeSH terms<\/p>\n

Intracellular Signaling Peptides and Proteins* \/ antagonists & inhibitors<\/p>\n

Intracellular Signaling Peptides and Proteins* \/ immunology<\/p>\n

Intracellular Signaling Peptides and Proteins* \/ metabolism<\/p>\n

Lung Neoplasms* \/ drug therapy<\/p>\n

Lung Neoplasms* \/ immunology<\/p>\n

Lung Neoplasms* \/ pathology<\/p>\n

Membrane Proteins* \/ antagonists & inhibitors<\/p>\n

Membrane Proteins* \/ metabolism<\/p>\n

Small Cell Lung Carcinoma* \/ drug therapy<\/p>\n

Small Cell Lung Carcinoma* \/ immunology<\/p>\n

Small Cell Lung Carcinoma* \/ pathology<\/p>\n

T-Lymphocytes* \/ drug effects<\/p>\n

T-Lymphocytes* \/ immunology<\/p>\n

Tumor Microenvironment \/ drug effects<\/p>\n

Tumor Microenvironment \/ immunology<\/p>\n

Substances<\/p>\n

Intracellular Signaling Peptides and Proteins<\/p>\n

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NLM<\/p>\n","protected":false},"excerpt":{"rendered":"Review . 2026 Sep 15;132(18):e70600. doi: 10.1002\/cncr.70600. Affiliations Expand Affiliation 1 Dana-Farber Cancer Institute, Boston, MA, USA. Item…\n","protected":false},"author":2,"featured_media":598576,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[294996,50,294995,134,5962,294998,294999,295000,295001,294997,295002,295003,295004,113924,295005,295006,271447,24720,118423,271446,111,139,22351,271445,69,294994,294993,271444,762,295007,295008,295009,295010,295011,295012,295013],"class_list":["post-598575","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-alissa-j-cooper","tag-animals","tag-doi10-1002-cncr-70600","tag-health","tag-humans","tag-immunotherapy-methods","tag-intracellular-signaling-peptides-and-proteins-antagonists-inhibitors","tag-intracellular-signaling-peptides-and-proteins-immunology","tag-intracellular-signaling-peptides-and-proteins-metabolism","tag-jacob-sands","tag-lung-neoplasms-drug-therapy","tag-lung-neoplasms-immunology","tag-lung-neoplasms-pathology","tag-medline","tag-membrane-proteins-antagonists-inhibitors","tag-membrane-proteins-metabolism","tag-national-center-for-biotechnology-information","tag-national-institutes-of-health","tag-national-library-of-medicine","tag-ncbi","tag-new-zealand","tag-newzealand","tag-nih","tag-nlm","tag-nz","tag-pmc13563195","tag-pmid42723523","tag-pubmed-abstract","tag-review","tag-small-cell-lung-carcinoma-drug-therapy","tag-small-cell-lung-carcinoma-immunology","tag-small-cell-lung-carcinoma-pathology","tag-t-lymphocytes-drug-effects","tag-t-lymphocytes-immunology","tag-tumor-microenvironment-drug-effects","tag-tumor-microenvironment-immunology"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts\/598575","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/comments?post=598575"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts\/598575\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/media\/598576"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/media?parent=598575"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/categories?post=598575"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/tags?post=598575"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}