The CTLA-4 x OX40 bispecific antibody ATOR-1015 induces anti-tumor effects through tumor-directed immune activation

Anne Månsson Kvarnhammar
Alligator Bioscience AB
March 30, 2019
J Immunother Cancer
https://pubmed.ncbi.nlm.nih.gov/30975201

This article is currently being updated. View its version on PubMed.

https://pubmed.ncbi.nlm.nih.gov/30975201

Research summary

This study introduces ATOR-1015, a human IgG1 bispecific antibody targeting CTLA-4 and OX40, designed to enhance tumor-directed immune activation. In vitro assays demonstrated that ATOR-1015 effectively activates T cells and depletes regulatory T cells (Tregs). In vivo, using human OX40 transgenic (Knockin) mice with established syngeneic tumors, ATOR-1015 treatment reduced tumor growth, improved survival, and induced long-term immunological memory. The antibody localized to the tumor microenvironment, decreased Treg frequency, and increased the number and activation of CD8+ T cells. Additionally, ATOR-1015 enhanced responses to PD-1 inhibition, suggesting its potential as a next-generation CTLA-4 targeting therapy with improved efficacy and reduced toxicity.

Key outcome of the study

ATOR-1015 induces T-cell activation and Treg depletion, reduces tumor growth, improves survival, and enhances the response to PD-1 inhibition in multiple syngeneic tumor models.

Mouse model

Human OX40 transgenic (Knockin) mice with established syngeneic tumors

TARGET:
CTLA4, TNFRSF4
CTLA-4, OX40

Keywords

Cancer immunotherapy, Bispecific antibody, CTLA-4, OX40, Treg depletion, T-cell activation

Technical specifications

Human OX40 transgenic Knockin model, Syngeneic tumor models, Bispecific antibody therapy

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