MRNA Delivery of a Bispecific Single-Domain Antibody to Polarize Tumor-Associated Macrophages and Synergize Immunotherapy against Liver Malignancies.

ABSTRACT: Liver malignancies are among the tumor types that are resistant to immune checkpoint inhibition therapy. Tumor-associated macrophages (TAMs) are highly enriched and play a major role in inducing immunosuppression in liver malignancies. Herein, CCL2 and CCL5 are screened as two major chemokines responsible for attracting TAM infiltration and inducing their polarization toward cancer-promoting M2-phenotype. To reverse this immunosuppressive process, an innovative single-domain antibody that bispecifically binds and neutralizes CCL2 and CCL5 (BisCCL2/5i) with high potency and specificity is directly evolved. mRNA encoding BisCCL2/5i is encapsulated in a clinically approved lipid nanoparticle platform, resulting in a liver-homing biomaterial that allows transient yet efficient expression of Bi

SUBMITTER: Wang Y 

PROVIDER: S-EPMC8240965 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature