Anti-LGALS3BP antibody-drug conjugate treatment induces durable and potent antitumor response in a preclinical model of adenoid cystic carcinoma

被引:6
作者
Capone, Emily [1 ,2 ]
Perrotti, Vittoria [3 ,10 ]
Cela, Ilaria [1 ,2 ]
Lattanzio, Rossano [1 ,2 ]
Togni, Lucrezia [4 ]
Rubini, Corrado [4 ]
Caponio, Vito Carlo Alberto [5 ]
Lo Muzio, Lorenzo [5 ]
Colasante, Martina [6 ]
Giansanti, Francesco [6 ]
Ippoliti, Rodolfo [6 ]
Iacobelli, Stefano [7 ]
Wick, Michael J. [8 ]
Burr, Nicole Spardy [9 ]
Sala, Gianluca [1 ,2 ,11 ]
机构
[1] Univ G Annunzio Chieti Pescara, Dept Innovat Technol Med & Dent, Pescara, Italy
[2] Univ G Annunzio Chieti Pescara, Ctr Adv Studies & Technol CAST, Pescara, Italy
[3] Univ G Annunzio Chieti Pescara, Dept Med Oral & Biotechnol Sci, Pescara, Italy
[4] Marche Polytech Univ, Dept Biomed Sci & Publ Hlth, Ancona, Italy
[5] Foggia Univ, Dept Clin & Expt Med, Foggia, Italy
[6] Univ LAquila, Dept Life Hlth & Environm Sci, Coppito, Italy
[7] MediaPharma s r l, Dept Oncol & Neurosci, Via Colonnetta 50-A, Chieti, Italy
[8] XenoSTART, San Antonio, TX USA
[9] Adenoid Cyst Carcinoma Res Fdn ACCRF, Needham, MA USA
[10] Univ G Annunzio Chieti Pescara, Res Ctr, UdA TechLab, I-66100 Pescara, Italy
[11] G Annunzio Univ Chieti Pescara, Ctr Adv Studies & Technol CAST, Dept Innovat Technol Med & Dent, Via L Polacchi 11, I-66110 Pescara, Italy
关键词
Oral cancer; Adenoid cystic carcinoma; LGALS3BP; Antibody-drug conjugate; Targeted therapy; Immunotherapy; HEAD;
D O I
10.1016/j.oraloncology.2023.106635
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Objectives: Adenoid cystic carcinoma (ACC) is a rare type of cancer that typically arises from glandular tissues, most commonly in the salivary glands. Although relatively rare, it represents a serious clinical issue as the management of the disease is highly complex being the only therapeutic options represented by invasive surgery and/or radiotherapy. In the present study, we have explored the potential of galectin-3 binding protein (LGALS3BP) as a novel target for antibody-drug conjugate (ADC) therapy in ACC. Materials and methods: RNAseq was conducted on a panel of 10 ACC patient-derived xenografts (PDX)s tissues and 6 normal salivary glands to analyze LGALS3BP gene expression. Protein expression was assessed in ACC PDX and primary tumor tissues using immunohistochemistry. Anti-LGALS3BP ADC named 1959-sss/DM4, was tested in high LGALS3BP expressing ACC PDX model ST1502B. Results: RNAseq analysis revealed that LGALS3BP expression was highly expressed in ACC PDX tissues compared to normal salivary gland tissues. As evaluated by immunohistochemical analysis, LGALS3BP protein was found to be heterogeneously expressed in 10 ACC PDX and in tumor tissues derived from a cohort of 37 ACC patients. Further, treatment with 1959-sss/DM4 ADC led to durable tumor growth inhibition (TGI) in 100% of animals without observed toxicity. Conclusions: Our study provides strong evidence that LGALS3BP is a promising therapeutic target for ACC, warranting further expedited preclinical and clinical investigation.
引用
收藏
页数:7
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