Nanobody-based heavy chain antibodies and chimeric antibodies.

Abstract

Nanobodies are the products of an intriguing invention in the evolution of immunoglobulins. This invention can be traced back approximately 45 million years to the common ancestor of extant dromedaries, camels, llamas, and alpacas. Next to conventional heterotetrameric H2L2 antibodies, these camelids produce homodimeric nanobody-based heavy chain antibodies, composed of shortened heavy chains that a lack the CH1 domain. Nanobodies against human target antigens are derived from immunized animals and/or synthetic nanobody libraries. As a robust, highly soluble, single immunoglobulin domain, a nanobody can easily be fused to another protein, for example to another nanobody and/or the hinge and constant domains of other immunoglobulins. Nanobody-derived heavy chain antibodies hold promise as a new form of immunotherapeutics.