HER2-targeted antibody-drug conjugate induces host immunity against cancer stem cells
| Autor: | Lu Wen, Frank I. Comer, Michael Oberst, Mary Jane Hinrichs, Tao Zhang, Alfred E. Chang, Yangyi Bao, Yuanyuan Liu, Hannah E. Dobson, Steven R. Coats, Qiao Li, Max S. Wicha, Fu Dai, You Qin, Leiming Xia |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Antibody-drug conjugate
Immunoconjugates Receptor ErbB-2 CD3 Clinical Biochemistry 01 natural sciences Biochemistry Article CD19 Mice Cancer stem cell Cell Line Tumor Drug Discovery Animals Humans skin and connective tissue diseases Molecular Biology Pharmacology Mice Inbred BALB C Tumor microenvironment biology 010405 organic chemistry 0104 chemical sciences Blockade body regions Neoplastic Stem Cells biology.protein Cancer research Molecular Medicine Female Antibody Conjugate |
| Zdroj: | Cell Chem Biol |
| ISSN: | 2451-9456 |
| Popis: | We previously tested HER2-targeted antibody drug conjugates (ADC) in immunocompromised (SCID) mice, precluding evaluation of host immunity, impact on cancer stem cells (CSCs), and potential benefit when combined with PD-L1 blockade. In this study, we tested HER2-targeted ADC in two immunocompetent mouse tumor models. HER2-targeted ADC specifically inhibited the growth of HER2-expressing tumors, prolonged animal survival, and reduced HER2(+) and PD-L1(+) cells. ADC plus anti-PD-L1 antibody augmented therapeutic efficacy, modulated immune gene signatures, increased the number and function of CD3(+) and CD19(+) tumor-infiltrating lymphocytes (TILs), induced tumor antigen specific immunological memory, stimulated B cell activation, differentiation, and IgG1 production both systemically and in the tumor microenvironment. In addition, ADC therapy modulated T cell subsets and their activation in TILs. Furthermore, HER2-targeted ADC reduced the number and tumorigenicity of ALDH(hi) CSCs. This study demonstrates that HER2-targeted ADC effectively targets ALDH(hi) CSCs and this effect is augmented by co-administration of anti-PD-L1 antibody. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|