Membrane protein leucine-rich repeat containing 15 (LRRC15) is known to be expressed in several solid tumors including osteosarcoma. ABBV-085, an antibody-drug conjugate against LRRC15, conjugated to monomethyl auristatin E (MMAE), was studied in osteosarcoma patient-derived xenografts (PDXs) by the Pediatric Preclinical Testing Consortium (PPTC). LRRC15 expression data were obtained from PPTC RNA-sequencing data for the PDX models. The TARGET database was mined for LRRC15 expression in human osteosarcoma. Protein expression was confirmed via IHC in three PDX models. Seven osteosarcoma PDX models (OS1, OS9, OS33, OS34, OS42, OS55, and OS60) with varying LRRC15 gene expression were studied. ABBV-085 was administered at 3 mg/kg (OS33), 6 mg/kg (all seven PDXs), and 12 mg/kg (OS60) weekly for 4 consecutive weeks via intraperitoneal injection. Control cohorts included vehicle and an isotype MMAE-linked antibody. Tumor volumes and responses were reported using PPTC statistical analysis. OS1, OS33, OS42, OS55, and OS60 had high LRRC15 expression while OS9 and OS34 had low LRRC15 expression. ABBV-085 inhibited tumor growth in six of seven PDX models as compared with vehicle control and significantly improved event-free survival in five of seven models as compared with isotype controls. Two models showed maintained complete responses while all others showed progressive disease. Response correlated with LRRC15 expression. ABBV-085's antitumor activity against osteosarcoma PDX suggests LRRC15 may be a rational target for pursuing clinical trials in patients with this disease.

/pdf/abbv-085-antibody-drug-conjugate-targeting-lrrc15-is-wtgk4egrlq.pdf

ABBV-085, Antibody-Drug Conjugate Targeting LRRC15, Is Effective in Osteosarcoma: A Report by the Pediatric Preclinical Testing Consortium.

The present disclosure provides antibodies, antibody binding fragments, and antibody drug conjugates that bind human LRRC15, their methods of making, and their uses to treat patients having cancer

Anti-huLRRC15 antibody drug conjugates and methods for their use

Immuno-oncology (IO) has emerged as one of the most promising approaches to improve the therapeutic efficacy and durability of clinical responses in cancer patients. However, despite the clinical breakthroughs achieved with immuno-therapies, such as checkpoint blockade, the overall proportion of patients experiencing durable responses to single agent immuno-therapy remains relatively small. Therefore, the real promise for most cancer patients does not lie in monotherapeutic approaches but in synergistic combination therapies, which combine the best of IO with the immune-promoting/supporting properties of other therapeutic modalities. The latter help to breach physical barriers, to overcome immunosuppressive networks within the tumor microenvironment and improve immune cell infiltration into tumors.

Combining ADCs with Immuno-Oncology Agents

Marine Isolates Streptomyces sp. MCCB 267 and Pseudonocardia sp. MCCB 268 as source of Potential Anticancer Molecules Ikarugamycin Type Polyketides and 1-Acetyl-β-Carboline: Isolation, Purification and in vitro Evaluation of Anticancer Activity

La presente invention concerne des anticorps, des fragments de liaison d'anticorps et des conjugues anticorps-medicaments qui se lient a la LRRC15 humaine, leurs procedes de preparation et leurs utilisations pour traiter des patients atteints d'un cancer.

Conjugués anticorps-medicaments anti-hulrrc15 et procédés d'utilisation de ces conjugués

ABBV-085 is a novel antibody–drug conjugate (ADC) that targets LRRC15 in the tumor microenvironment

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ABBV-085 is a novel antibody–drug conjugate (ADC) that targets LRRC15 in the tumor microenvironment