Leadartis discloses the project: ATTACK-Cancer immunotherapy by bispecific antibodies that recruit T lymphocytes

11-12-2018

LeadArtis is pleased to announce its participation as coordinator of the ATTACK project (Cancer immunotherapy by bispecific antibodies that recruit T lymphocytes) funded Spanish Ministry of Science, Innovation and Universities (MICINN) under the RETOS 2017 Collaboration program. ATTACK counts with collaborators such as the internationally regarded: Fundación para la Investigación Biomédica del Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid and Centro Nacional de Investigaciones Oncológicas (CNIO). The MICINN’s funding demonstrates the support of LeadArtis technology and objectives.

Redirecting the activity of T cells with bispecific antibodies against tumor cells independently of their T-cell receptor (TCR) specificity is a potent approach to treat cancer. Our concept is based on recognition of a cell surface Tumor -associated antigen (TAA) and simultaneous binding to CD3ε within the TCR complex triggering T cell tumor killing activity. Trimerbody® is a novel class of proprietary multivalent and multispecific antibody technology that allows rapid generation of novel cancer therapeutics. Asymmetric Tandem Trimerbody for T cell Activation and Cancer Killing (ATTACK) is a technology evolution generated by fusing single-domain antibodies (VHH) or antibody mimetics to the N-terminus of the collagen TrImErization (TIE) domain and an antigen-binding domain to the C-terminus. ATTACKs are soluble and functional single polypeptide proteins produced by standard mammalian cell systems which exhibit specific and high affinity TAA-binding and low affinity CD3ε-binding, permitting the generation of multispecific antibodies from pre-existent single-domain antibodies. As this new format targets up to three pathogenic pathways/TAAs is a great tactic for redirecting the cytotoxic activity of T cells preventing cancer resistance.

ATTACK molecules are designed to specifically kill cancer cells overcoming the limitations of earlier T cell bispecifics. The multivalent TAA targeting improves anti-tumor activity, the Fc domain absence precludes the unwanted unspecific pro-inflammatory cell activation and associated adverse effects; Further, ATTACKs are designed with one or more TAA specificities to fine-tune cancer killing and their unique structural/functional properties form the basis their multiple competitive advantages.

Our lead product incorporates an immunecheckpoint blocking antibody further to two TAA-specific moieties. The immune checkpoint has an inhibitory function on T and B cells, and is important in peripheral tolerance, its ligand can be ectopically expressed on the surface of malignant cells thus inhibiting tumor T cell killing. Therefore the interference of such axis reinvigorates tumor-specific T lymphocytes and tumor rejection. In this context, we propose a product with several advantages: 1) increasing tumor specificity by targeting two different TAAs on the tumor cell surface, 2) blocking the immune check point inhibitory route and 3) T cell cytotoxic activity redirection through CD3 stimulation.

LeadArtis is the leading company aiming to bring to the market cancer immunotherapeutic trimerbodies. Despite recent advances in the field, most of the current initiatives are early stage and exploratory. Currently, most of current immune-checkpoint blockers in development are conventional monoclonal antibodies (mAbs); comparatively, recombinant antibody technologies are strongly positioned and shortly will become preferred for clinically validated mechanisms of action. The trimerbody added value is multivalence and multispecificity, small size & ease of manufacturing to generate more effective compounds. 

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