Triple-Negative Breast Cancer or TNBC is a clinical classification for an aggressive type of breast cancer, based upon the low level of expression, or absence of expression, of 3 key markers:  Epidermal Growth Factor Receptor 2 (HER2), Estrogen Receptor (ER) and the Progesterone Receptor (PR).  These subtypes constitute about 15% of all breast cancers. Currently, there is no specific systemic regimen or targeted therapy for breast tumours with the triple-negative phenotype (ER-negative, PR-negative, and HER2-negative). Rather various approaches based on chemotherapy, targeting DNA, microtubules and Epidermal Growth Factor Receptor 1 (EGFR), seem to be the only hope available to date, with limited efficacy and toxicity being observed, therefore creating an unmet need for treating such an aggressive disease, with a very poor prognosis.   

Biotecnol  is studying potential undisclosed target surface-expressed antigens for being used as targets in TNBC (T1, T2, T3, T4).  Using its Tribody platform, Biotecnol is designing and testing the efficacy of its multi-targeting antibody derivatives in order to address TNBC, whereby, strategies using  bi and tri-specific antibodies using a T-cell recruitment functionality via an anti-CD3 effector function is being employed to redirect T cells against cancer target cells.

Target cells are killed when cytotoxic T lymphocytes are tethered to tumour cells and simultaneously triggered by one arm of the bispecific antibody that interacted with the T-cell receptor (TCR)–CD3 complex.

The use of the monomorphic CD3 complex for triggering T cells circumvented the restrictions of clonotypic T-cell specificity and enabled a polyclonal cytotoxic T cell response against tumour cells expressing the target antigen, which is recognized by the second arm of the bispecific antibody. It is important to note that cytotoxic T lymphocytes (CTL), which are considered to be the most potent killer cells of the immune system, cannot be engaged by conventional monoclonal antibodies because they lack Fcγ receptors. Therefore bi-(or tri-) specific recombinant antibodies targeting  more than one target antigen and in addition recruit CTLs, have the potential to be much more effective than conventional monoclonal antibody therapies.