Abstract: A receiver circuit comprising: an input-pin; a receiver-input-node; a ground-pin; an internal-node that is connected to the input-pin; and a MOSFET. The MOSFET has a conduction channel connected in series between the internal-node and the receiver-input-terminal; and a gate terminal, the voltage at which sets the conductivity of the conduction channel. The receiver circuit also includes an amplifier that: has an input terminal that is connected to the internal-node; and provides a voltage control signal to the gate terminal of the MOSFET such that the voltage at the internal-node with respect to the ground-pin is constant.

Abstract: Inventors have generated two human anti-cath-D scFv fragments cloned in the human IgG1? format (F1 and E2) that efficiently bind to human and mouse cath-D, even at the acidic pH of the TNBC microenvironment. F1 and E2 accumulated in TNBC MDAMB-231 tumor xenografts, inhibited tumor growth and improved mice survival without apparent toxicity. Using this xenograft model, they found that the Fc function of F1 was essential for maximal tumor inhibition. Inventors have shown that the anti-cath-D antibody F1 treatment prevented the recruitment of tumor-associated macrophages and myeloid-derived suppressor cells within the tumor, a specific effect associated with a less immunosuppressive tumor microenvironment. Moreover F1 inhibited tumor growth of TNBC patient-derived xenografts (PDXs). This preclinical proof-of-concept study validates the feasibility and efficacy of an immunomodulatory antibody-based strategy against cath-D to treat patients with TNBC.