Searchable abstracts of presentations at key conferences in endocrinology

ea0099p301 | Endocrine-Related Cancer | ECE2024

Dual targeting Boolean logic gate CAR-T cells for selective tumor antigen encounter exert potent antitumor efficacy in advanced adrenocortical carcinoma

Schauer Marc Philipp , Stabile Andrea , Landwehr Laura-Sophie , Altieri Barbara , Fassnacht Martin , Weber Justus , Hudecek Michael

Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy that produces glucocorticoids in 60% of cases causing clinically relevant hypercortisolism. Since, we observed in another study, that shaping these immunosuppressive and life-threatining properties with corticosteroid inhibitors not only led to a glucocorticoid receptor-related downregulation of ROR1 but also to the upregulation of another promising membrane bound oncogenic antigen* (AG), we sought to...

ea0099rc7.3 | Rapid Communications 7: Endocrine-related Cancer | ECE2024

Activating the intratumoral IFNγR-pathway in adrenocortical carcinoma potently enhances antitumor functionality of CAR-T cells by modulating immune cell adhesion and responsiveness

Schauer Marc Philipp , Landwehr Laura-Sophie , Weber Justus , Altieri Barbara , Sbiera Silviu , Kroiss Matthias , Fassnacht Martin , Hudecek Michael

Background: Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine disease in which 60% of patients show endogenous glucocorticoid (GC) secretion that potentially contributes to a lack of immune cell infiltration and limited efficacy of immunotherapeutic approaches. In another study, we already demonstrated potent antitumor efficacy or ROR1 CAR-T cells in preclinical models of ACC. Nevertheless, solid tumors often show cell intrinsic resistance mechanisms to CAR-T c...

ea0090oc6.4 | Oral Communications 6: Endocrine-related Cancer | ECE2023

CAR-T cell therapy exerts effective antitumor efficacy under immunosuppressive conditions in adrenocortical carcinoma

Philipp Schauer Marc , Landwehr Laura-Sophie , Justus Weber , Altieri Barbara , Rodrigo Redundo-Frutos , Tanja Maier , Daniel Oppelt , Kroiss Matthias , Sbiera Silviu , Michael Hudecek , Fassnacht Martin

Background: Adrenocortical carcinoma (ACC) is a very rare and aggressive, endocrine malignancy with still limited treatment options. Approximately 60% of patients with ACC show endogenous glucocorticoid excess which could be one potential cause, why first clinical trials with immunotherapies, like immune checkpoint inhibitors, showed only modest results. Due to the lack of an ACC-specific antigen structure, other immunotherapeutic approaches, like specialized cancer treatments...

ea0093oc20 | Oral communication 3: Adrenal Tumors and Neuroendocrine Tumors | EYES2023

ROR-1 specific CAR-T cells with CRISPR/CAS9 mediated glucocorticoid receptor-knockout exert potent antitumor efficacy in advanced adrenocortical carcinoma

Schauer Marc Philipp , Altieri Barbara , Redondo-Frutos Rodrigo A , Spieler Peter , Maier Tanja , Oppelt Daniel , Kroiss Matthias , Sbiera Silviu , Weber Justus , Fassnacht Martin , Landwehr Laura-Sophie , Hudecek Michael

# These authors contributed equallyIntroduction: Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy with poor prognosis and limited treatment options. In addition, ACC is characterized by endogenous glucocorticoid (GC) excess in 60% of cases which is hypothesized to be one reason, why first clinical trials evaluating the potency of immune checkpoint blockade showed only modest results. Here, we report the identificati...

ea0099oc7.1 | Oral Communications 7: Endocrine-related Cancer | ECE2024

CRISPR/Cas9-mediated glucocorticoid receptor knockout effectively enhances antitumor efficacy of ROR1 specific CAR-T cells in advanced adrenocortical carcinoma

Schauer Marc Philipp , Weber Justus , Landwehr Laura-Sophie , Spieler Peter , Altieri Barbara , Maier Tanja , Kroiss Matthias , Kircher Stefan , Kurlbaum Max , Tony Liz , Sbiera Silviu , Fassnacht Martin , Hudecek Michael

Background: Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy with poor prognosis and very limited treatment options in advanced disease. The only curative approach is complete surgical resection. Additionally, 60% of patients show endogenous glucocorticoid (GC) excess with clinical apparent hypercortisolism and low to no immune cell infiltration. To date, no therapeutically relevant surface markers are known for ACC, which is why it has not been con...

ea0090oc6.5 | Oral Communications 6: Endocrine-related Cancer | ECE2023

WEE1 kinase inhibitor, adavosertib (AZD1775), as a novel potential therapeutic strategy in advanced adrenocortical carcinoma

Tamburello Mariangela , Sbiera Silviu , Justus Weber , Lippert Juliane , Detomas Mario , Schauer Marc Philipp , Urlaub Hanna , Steinhauer Sonja , Kimpel Otilia , Landwehr Laura-Sophie , Constanze Hantel , Sigala Sandra , Ronchi Cristina , Hudecek Michael , Katja Kiseljak-Vassiliades , Fassnacht Martin , Altieri Barbara

Background: Adrenocortical cancer (ACC) is a rare malignant neoplasm with a dismal prognosis, particularly in advanced disease. For these patients only limited therapeutic options are available. Adavosertib (AZD1775) is a potent inhibitor of tyrosine kinase WEE1 that regulates cell cycle checkpoints, slowing cell cycle progression and leading to mitotic entry in the presence of DNA damage. Therefore, its use could potentiate existing DNA damage-based therapies. Here, we evalua...