Chimeric antigen receptor based on BMCA nano-antibody sequence and application thereof

Abstract

The invention relates to the technical field of cellular immunity, and discloses a chimeric antigen receptor based on a BMCA nano-antibody sequence and an application thereof, wherein the chimeric antigen receptor includes an extracellular structural domain, a transmembrane structural domain and a primary signal transduction domain. The extracellular structural domain includes an alpaca anti-BCMAantibody or an antigen binding fragment of an alpaca BCMA polypeptide or multiple epitopes. The chimeric antigen receptor is mainly applied in tumor treatment drugs, tumors are blood-related tumor diseases, and the blood-related tumor diseases mainly include various types of leukemia and malignant lymphoma. According to the chimeric antigen receptor based on the BMCA nano-antibody sequence and theapplication thereof, the expression sequence is shorter, and the limited space of a lentiviral vector is saved. The chimeric antigen receptor T cell constructed based on the antibody has better specificity and stronger tumor killing ability.

Description

technical field [0001] The invention relates to the technical field of cellular immunity, in particular to a chimeric antigen receptor based on BMCA nanobody sequence and its application. Background technique [0002] In recent years, chimeric antigen receptor (chimeric angiten receptor, CAR) modified T cell-based adoptive immunotherapy of tumors has made great progress. The modified T cells not only have the killing ability to target tumor cells, but also can overcome the local immunosuppressive microenvironment of the tumor and break the state of host immune tolerance. CAR has been developed to the fourth generation through continuous improvement. The first-generation CAR is mainly composed of scFv and ITAM (usually CD3ζ) that recognize tumor-associated antigens, but because only CD3ζ activates the signal, T cells cannot fully proliferate, and the activated T cells survive in vivo for a short time. The second-generation CAR adds a co-stimulatory molecule such as CD28, CD...

AI Technical Summary

Problems solved by technology

[0005] Aiming at the deficiencies of the prior art, the present invention provides a chimeric antigen receptor based on the BMCA nanobody sequence and its application, which has a shorter expression sequence and saves limited lentiviral vector space. The chimeric antigen constructed based on the antibody Recipient T cells have better specificity and stronger tumor killing ability, which solves the common CAR antigen-binding region composed of human or mouse heavy chain and light chain variable regions. The scFv expression sequence is longer and tumor killing The problem of low ability