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T-cell recruiting Tribody™ molecules may prove to be less toxic and more effective agents to address cardiotoxicity and resistance in gastric and breast cancer.

Biotecnol and University of Naples published a study on Journal of Immunology, Volume 42 Issue 1: pg 1-10,where it was shown that T-cell recruiting bispecific antibody derivatives (TRBA) offer a more effective alternative to standard antibody therapy. The team evaluated a panel of TRBAs targeting 3 different epitopes on the HER2 receptor either in a bivalent targeting tribody structure or as a monovalent scFv-fusion (BiTE format) for binding, cytotoxicity on Trastuzumab-resistant cell lines, and induction of cardiotoxicity. All three TRBAs did bind with high affinity to the HER2 extracellular domain and a large panel of HER2-positive tumour cells. Tribodies had an increased in vitro cytotoxic potency as compared to BiTEs. It was noted that Tribodies targeting the epitopes on ErbB2 receptor domains I and II bind and activate lysis of mammary and gastric tumour cells more efficiently than a Tribody targeting the Trastuzumab epitope on domain IV. The first 2 are also active on Trastuzumab-resistant cancer cells lacking or masking the epitope recognized by Trastuzumab. None of the Tribodies studied showed significant toxicity on human cardiomyocytes. Altogether these results make these novel anti-HER2 bispecific Tribodies candidates for therapeutic development for treating HER2-positive Trastuzumab-resistant cancer patients.

About Biotecnol Limited

Biotecnol Limited is an immuno-oncology company developing innovative immune-function activating and immune-function modulation approaches for treating cancer. These approaches seek to recruit or to modulate the body’s own immune defences such as T cells and NK cells to kill tumours. Biotecnol multi-specific antibody products are based on its proprietary Tribody™ and Trisoma® platforms, which are comprised of a variety of formats with key properties. Under the Trisoma® platform, Biotecnol has developed a novel format known as Targeted T-cell Engaging Agonistic Response Modifiers or iChecks™.These products aim at improving tumour cell dependent T-cell or NK-cell activation. The iCheck™ formats are expected to achieve a more localized immune-function activation and obtain less or no systemic toxicity, whilst having an increased therapeutic index.These are potentially safer and more effective drugs for treating highly-heterogeneous and highly-aggressive solid tumours.

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