Delta-like 1 homolog (DLK1) as a possible therapeutic target and its application to radioimmunotherapy using 125I-labelled anti-DLK1 antibody in lung cancer models (HOT1801 and FIGHT004)

Takagi, Hironori; Muto, Satoshi; Yokouchi, Hiroshi; Nishihara, Hiroshi; Harada, Toshiyuki; Yamaguchi, H.; Mine, Hayato; Watanabe, Masayuki; Ozaki, Yuki; Inoue, Takuya; Yamaura, Takumi; Fukuhara, Mitsuro; Okabe, Naoyuki; Matsumura, Yuki; Hasegawa, T.; Osugi, Jun; Hoshino, Mika; Higuchi, Mitsunori; Shio, Yutaka; Kanno, Ryuzo; Aoki, Miho; Tan, Chengbo; Shimoyama, Saki; Yamazaki, Shigeo; Kikuchi, Hajime; Sakakibara‐Konishi, Jun; Oizumi, Satoshi; Harada, Masao; Akie, Kenji; Sugaya, Fumiko; Fujita, Yuka; Takamura, Kei; Kojima, Takao; Honjo, Osamu; Minami, Yoshinori; Nishimura, Masaharu; Dosaka‐Akita, Hirotoshi; Nakamura, Koji; Inano, Akihiro; Isobe, Hiroshi; Suzuki, Hiroyuki

doi:10.1016/j.lungcan.2021.01.014

Cited by 13 publications

(9 citation statements)

References 38 publications

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“…Many studies show that the high frequency of DLK1 expression in different malignancies including colon, breast, brain, gastro, liver, lung, pancreas, renal, sarcoma and other endocrine‐related cancers 31 . To date, in addition to the vaccine against DLK1 in renal cell carcinoma mouse model 50 and anti‐DLK1 iodine 125‐labelled antibody in lung cancer mouse model, 51 the experimental therapeutic approaches targeting DLK1 have rarely been studied. Except for human HCC, a previous report indicated that DLK1 is an epigenetically regulated immunotherapeutic target in neuroblastoma 30 .…”

Section: Discussionmentioning

confidence: 99%

DLK1‐directed chimeric antigen receptor T‐cell therapy for hepatocellular carcinoma

Zhai

Huang

et al. 2022

Liver International

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Hepatocellular carcinoma (HCC) is one of the most common malignant tumours, accounting for 85%-90% of primary liver cancers, 1 and ranks the fourth leading cause of cancer-related mortality globally. 2 The poor prognosis for most HCC patients can be attributed to a more advanced stage at diagnosis, liver dysfunction and spread of tumour cells. However, current systemic treatment strategies for HCC only demonstrated a modest effect on patient survival, 3 and therefore the novel effective therapeutic strategies for the management of HCC are urgently needed.

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Section: Discussionmentioning

confidence: 99%

DLK1‐directed chimeric antigen receptor T‐cell therapy for hepatocellular carcinoma

Zhai

Huang

et al. 2022

Liver International

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“…8,50,[86][87][88][89][90][91] In particular, DLK1 overexpression has been associated with increased aggressiveness and poor outcome in glioblastoma (GBM), hepatocellular carcinoma, ovarian, prostate, and lung cancer. 11,47,49,50,90,92,93 Indeed, more and more evidence suggests that therapy resistance and relapse are mostly due to the survival of cancer cells presenting with the stemness phenotype, typically enriched in specialized microenvironmental niches, and that DLK1 can play a role in the regulation and maintenance of this phenotype.…”

Section: Dlk1 In Cancer and Cancer Stem Cell Nichesmentioning

confidence: 99%

“…In particular, DLK1 overexpression has been associated with increased aggressiveness and poor outcome in glioblastoma (GBM), hepatocellular carcinoma, ovarian, prostate, and lung cancer. 11 , 47 , 49 , 50 , 90 , 92 , 93 …”

Section: Dlk1 In Cancer and Cancer Stem Cell Nichesmentioning

confidence: 99%

Emerging Roles of DLK1 in the Stem Cell Niche and Cancer Stemness

Grassi

Pietras

2021

J Histochem Cytochem.

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DLK1 is a maternally imprinted, paternally expressed gene coding for the transmembrane protein Delta-like homologue 1 (DLK1), a non-canonical NOTCH ligand with well-described roles during development, and tumor-supportive functions in several aggressive cancer forms. Here, we review the many functions of DLK1 as a regulator of stem cell pools and tissue differentiation in tissues such as brain, muscle, and liver. Furthermore, we review recent evidence supporting roles for DLK1 in the maintenance of aggressive stem cell characteristics of tumor cells, specifically focusing on central nervous system tumors, neuroblastoma, and hepatocellular carcinoma. We discuss NOTCH -dependent as well as NOTCH-independent functions of DLK1, and focus particularly on the complex pattern of DLK1 expression and cleavage that is finely regulated from a spatial and temporal perspective. Progress in recent years suggest differential functions of extracellular, soluble DLK1 as a paracrine stem cell niche-secreted factor, and has revealed a role for the intracellular domain of DLK1 in cell signaling and tumor stemness. A better understanding of DLK1 regulation and signaling may enable therapeutic targeting of cancer stemness by interfering with DLK1 release and/or intracellular signaling.

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“…Non-small-cell lung cancer (NSCLC) accounts for more than 80% of lung cancer cases. Many cases are already advanced at the time of diagnosis ( 15 , 16 ), therefore, NSCLC is characterized by high morbidity and mortality ( 17 ) and an adverse prognosis ( 18 , 19 ). So, it is also necessary to find new treatments ( 20 ).…”

Section: Introductionmentioning

confidence: 99%

131I-Caerin 1.1 and 131I-Caerin 1.9 for the treatment of non-small-cell lung cancer

Liu

He²,

Xiao³

et al. 2022

Front. Oncol.

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ObjectiveTo investigate the effect of the 131I-labeled high-affinity peptides Caerin 1.1 and Caerin 1.9 for the treatment of A549 human NSCLC cells.Methods① 3-[4,5-Dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and plate clone formation assays were performed to confirm the in vitro anti-tumor activity of Caerin 1.1 and Caerin 1.9. ② Chloramine-T was used to label Caerin 1.1 and Caerin 1.9 with 131I, and the Cell Counting Kit 8 assay was performed to analyze the inhibitory effect of unlabeled Caerin 1.1, unlabeled Caerin 1.9, 131I-labeled Caerin 1.1, and 131I-labeled Caerin 1.9 on the proliferation of NSCLC cells. An A549 NSCLC nude mouse model was established to investigate the in vivo anti-tumor activity of unlabeled Caerin 1.1, unlabeled Caerin 1.9, 131I-labeled Caerin 1.1, and 131I-labeled Caerin 1.9.Results① Caerin 1.1 and Caerin 1.9 inhibited the proliferation of NSCLC cells in vitro in a concentration-dependent manner. The half-maximal inhibitory concentration was 16.26 µg/ml and 17.46 µg/ml, respectively, with no significant intergroup difference (P>0.05). ② 131I-labeled Caerin 1.1 and 131I-labeled Caerin 1.9 were equally effective and were superior to their unlabeled versions in their ability to inhibit the proliferation and growth of NSCLC cells (P>0.05).Conclusions131I-labeled Caerin 1.1 and 131I-labeled Caerin 1.9 inhibit the proliferation and growth of NSCLC cells and may become potential treatments for NSCLC.

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Delta-like 1 homolog (DLK1) as a possible therapeutic target and its application to radioimmunotherapy using 125I-labelled anti-DLK1 antibody in lung cancer models (HOT1801 and FIGHT004)

Cited by 13 publications

References 38 publications

DLK1‐directed chimeric antigen receptor T‐cell therapy for hepatocellular carcinoma

DLK1‐directed chimeric antigen receptor T‐cell therapy for hepatocellular carcinoma

Emerging Roles of DLK1 in the Stem Cell Niche and Cancer Stemness

131I-Caerin 1.1 and 131I-Caerin 1.9 for the treatment of non-small-cell lung cancer

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