Tandem CAR-T cells targeting CD70 and B7-H3 exhibit potent preclinical activity against multiple solid tumors.

Theranostics
Meijia YangAiping Tong

Abstract

Purpose: Given that heterogeneous expression and variants of antigens on solid tumors are responsible for relapse after chimeric antigen receptor (CAR)-T cell therapy, we hypothesized that combinatorial targeting two tumor-associated antigens would lessen this problem and enhance the antitumor activity of T cells. Methods: The co-expression level of CD70 and B7-H3 was analyzed in multiple tumor tissue samples. Further, two putative antigens were identified in The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis database. Two CD70 targeted CARs with different antigen binding domain, truncated CD27 and CD70 specific single-chain antibody fragment (scFv), were designed to screen a more suitable target-antigen binding moiety. Accordingly, we designed a bivalent tandem CAR (TanCAR) and further assessed the anti-tumor efficacy of TanCAR-T cells in vitro and in vivo. Results: Our results indicated that co-expression of CD70 and B7-H3 was observed on multiple tumor types including kidney, breast, esophageal, liver, colon cancer, glioma as well as melanoma. The CD70 targeted CAR-T cells with binding moiety of CD70 specific scFv exhibit a higher affinity and antitumor effect against CD70+ tumor cells. TanCAR-T cells...Continue Reading

Citations

Jan 23, 2021·Expert Review of Clinical Immunology·Azadehsadat RazaviNima Rezaei
Jun 12, 2021·Frontiers in Neuroscience·Luke MaggsSoldano Ferrone
Jun 25, 2021·Frontiers in Immunology·Concetta QuintarelliBiagio De Angelis
Aug 6, 2021·Frontiers in Immunology·Wu-Tong Zhou, Wei-Lin Jin
Jul 25, 2021·Cancers·Chirayu R ChokshiSheila K Singh
Aug 31, 2021·World Journal of Gastrointestinal Oncology·Petar RasicDjordje Savic

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Methods Mentioned

BETA
fluorescence-activated cell sorter
gel filtration
transfection
ELISA
xenografts
RNA-seq
flow cytometry
xenograft

Software Mentioned

Gene Expression Profiling Interactive Analysis ( GEPIA
FlowJo
GeneOptimizer
GENEWIZ
GraphPad Prism
Living Image

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