ABBV-085, Antibody–Drug Conjugate Targeting LRRC15, Is Effective in Osteosarcoma: A Report by the Pediatric Preclinical Testing Consortium
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Abstract
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.
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Several emerging immune-based approaches other than immune-checkpoint inhibitors have generated encouraging preclinical results in osteosarcoma.
“although several emerging immune-based approaches other than the use of ICIs have generated encouraging preclinical results 86,87,88,89,91 .”
From Osteosarcoma (2022) · cites this paper as [86]
Preclinical data evaluating antibody-drug conjugates targeting B7H3, LRRC15 and HER2 in osteosarcoma have been particularly promising and are rapidly moving to and through clinical trials.
“Preclinical data evaluating antibody-drug conjugates, such as those targeting B7H3 (ref.90 ), LRRC15 (ref.86 ) and HER2 (ref.91 ), have been particularly promising and are rapidly moving to and through clinical trials.”
From Osteosarcoma (2022) · cites this paper as [86]
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- Authors
- Hingorani, P., Roth, M. E., Wang, Y., Zhang, W., Gill, J. B., Harrison, D. J., Teicher, B., Erickson, S., Gatto, G., Smith, M. A., Kolb, E. A., & Gorlick, R.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- National Cancer Institute (US)
- RTI International (US)
- Alfred I. duPont Hospital for Children (US)
- ORCID
- Venue
- Molecular Cancer Therapeutics
- Published
- 2021-03-01
- Volume
- 20
- Issue
- 3
- Pages
- 535-540
- ISSN
- 1535-7163 (ISSN-L)
- 1538-8514
- PMC
- PMC8715742
- OpenAlex
- W3110828287
- Cited by
- 41
- References
- 20
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 6 · 2023: 5 · 2022: 12 · 2021: 3
- FWCI
- 2.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Cancer Therapeutics (publishedVersion, public-domain)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- HHS | NIH | National Cancer Institute (5U01CA199221-06)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Immunology and Microbiology › Immunology › Toxin Mechanisms and Immunotoxins
- Keywords
- antibody-drug conjugates, LRRC15, osteosarcoma, monomethyl auristatin E, patient-derived xenografts, tumor growth inhibition, event-free survival, biomarker expression, childhood cancer, targeted therapy
- MeSH terms
- Animals, Child, Female, Humans, Membrane Proteins, Osteosarcoma, Gene Expression, Immunoconjugates, Mice
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