Synthetic biology-based ADCC technology
A novel synthetic biology-based ADCC technology is provided that enhances or enables ADCC response. The novel ADCC technology can be used to prevent or treat cancers, infectious, inflammatory or autoimmune diseases, and other diseases where elimination of diseased cells is desirable.
1. A transmembrane chimeric receptor comprising an ectodomain, a transmembrane domain, and an endodomain for mediating antibody-dependent cellular cytotoxicity (ADCC) activation and amplification, wherein the ectodomain comprises the three immunoglobulin or immunoglobulin-like folds in the extracellular domain of CD64, wherein said ectodomain is selected based on boundaries of exons or domains in CD64; wherein the endodomain comprises (a) an ADCC signaling module, and (b) one or more ADCC amplification modules that enhance the survival and/or proliferation of a host immune effector cell; and
wherein the transmembrane chimeric receptor comprises an amino acid sequence having the sequence selected from the group consisting of SEQ ID NOs: 2, 4, 6, 8, and 10.
2. The transmembrane chimeric receptor of claim 1 , comprising the amino acid sequence of SEQ ID NO: 6, and wherein the transmembrane domain comprises the transmembrane domain of CD16a.
3. The transmembrane chimeric receptor of claim 1 , comprising the amino acid sequence of SEQ ID NO: 10.
4. An immune effector cell infected or transfected ex vivo with a genetic construct encoding the transmembrane chimeric receptor of claim 1 .
5. The immune effector cell of claim 4 , selected from the group consisting of cytotoxic T lymphocyte, a natural killer cell, an eosinophil, a macrophage, a neutrophil, a basophil, a monocyte, and a B cell.
6. A transmembrane chimeric receptor comprising an amino acid sequence having the sequence selected from the group consisting of SEQ ID NOs: 2, 4, 6, 8, and 10.
7. An immune effector cell infected or transfected ex vivo with a genetic construct encoding the transmembrane chimeric receptor of claim 6 .
8. The immune effector cell of claim 7 , selected from the group consisting of cytotoxic T lymphocyte, a natural killer cell, an eosinophil, a macrophage, a neutrophil, a basophil, a monocyte, and a B cell.