Development and Evaluation of CART Targeting Bcma with Humanized Alpaca-Derived Single-Domain Antibody As Antigen Recognition Domain

Chimeric antigen receptor T cells (CART) targeting CD19 have shown substantial activity against leukemia and lymphoma, which motivated developing CART cell therapy for Multiple myeloma (MM). B cell maturation antigen (BCMA) is the target molecule in MM. Several kinds of CART targeting BCMA have been created from 2016. Among these, the Bluebird Bio uses the humanized murine BCMA scFv to make CART, the Nanjing Legend company uses the single-domain antibody targeting BCMA to make CART.The single-domain antibody refers to the heavy chain antibody naturally present in camel species, which has no light chain. All VHh (Variable region of Heavy chain in heavy chain antibody) domains from the immunized alpaca were cloned into the phage-display library, then specific VHhs were screened out by solid-phase ELISA. Not like scFv using the linker region to connect the VH and VL to obtain the single chain region, the VHh itself is one single chain, which make it very suitable for making the recognition domain of CART. In order to increase the avidity, the Nanjing Legend company uses two tandem VHhs for binding BCMA. However, the single domain antibody has the capacity to bind the target molecule with very high affinity, one VHh should be able to bind BCMA tightly. To this aim, using our platform of single-domain antibody discovery and CART development, we successfully obtain the CART targeting BCMA (CART-BCMA) just using one VHh for recognizing the BCMA on tumor cells.Firstly, we immunized t...

Source: Blood - November 21, 2018 Category: Hematology Authors: Han, L., Gao, Q., Zhou, K., Yin, Q., Fang, B., Zhou, J., Zhu, X., Liu, D., Zhang, J., Du, H., Li, H., Song, Y. Tags: 653. Myeloma: Therapy, excluding Transplantation: Poster I Source Type: research