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DIPG is noted for its lethality, as fewer than 1% of patients survive to five years. Multiple clinical trials involving chemotherapy, radiotherapy, and\/or targeted therapy have all failed to improve clinical outcomes. Recently, high-throughput sequencing of a cohort of DIPG samples identified potential therapeutic targets, including interleukin 13 receptor subunit alpha 2 (IL13R\u03b12) which was expressed in multiple tumor samples and comparably absent in normal brain tissue, identifying IL13R\u03b12 as a potential therapeutic target in DIPG. In this work, we investigated the role of IL13R\u03b12 signaling in progression and invasion of DIPG and viability of IL13R\u03b12 as a therapeutic target through the use of immunoconjugate agents. We discovered that IL13R\u03b12 stimulation via canonical ligands demonstrates minimal impact on both the cellular proliferation and cellular invasion of DIPG cells, suggesting IL13R\u03b12 signaling is non-essential for DIPG progression in vitro. However, exposure to an anti-IL13R\u03b12 antibody\u2013drug conjugate demonstrated potent pharmacological response in DIPG cell models both in vitro and ex ovo in a manner strongly associated with IL13R\u03b12 expression, supporting the potential use of targeting IL13R\u03b12 as a DIPG therapy. However, the tested ADC was effective in most but not all cell models, thus selection of the optimal payload will be essential for clinical translation of an anti-IL13R\u03b12 ADC for DIPG.<\/jats:p>","DOI":"10.1186\/s40478-021-01184-9","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T10:03:24Z","timestamp":1621245804000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Design considerations of an IL13R\u03b12 antibody\u2013drug conjugate for diffuse intrinsic pontine glioma"],"prefix":"10.1186","volume":"9","author":[{"given":"Xiaolei","family":"Lian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Kats","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Rasmussen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah R.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anju","family":"Karki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Keller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8666-3152","authenticated-orcid":false,"given":"Noah E.","family":"Berlow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"key":"1184_CR1","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1111\/imr.12773","volume":"290","author":"D Akhavan","year":"2019","unstructured":"Akhavan D, Alizadeh D, Wang D, Weist MR, Shepphird JK, Brown CE (2019) CAR T cells for brain tumors: lessons learned and road ahead. 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