CD16 CAR-T cells enhance antitumor activity of CpG ODN-loaded nanoparticle-adjuvanted tumor antigen-derived vaccinevia ADCC approach

Xiaofei Zhang; Qin Hu; Xuesong He; Xinyue Cui; Zhaoyuan Liang; Li Wang; Xiongwei Deng; Ze Zhang; Wang Sheng; Xiaodong D Han

doi:10.1186/s12951-023-01900-8

CD16 CAR-T cells enhance antitumor activity of CpG ODN-loaded nanoparticle-adjuvanted tumor antigen-derived vaccinevia ADCC approach

J Nanobiotechnology. 2023 May 20;21(1):159. doi: 10.1186/s12951-023-01900-8.

Authors

Xiaofei Zhang¹, Qin Hu², Xuesong He², Xinyue Cui², Zhaoyuan Liang², Li Wang¹, Xiongwei Deng², Ze Zhang^{1

3

4}, Wang Sheng^{5

6}, Xiaodong D Han^{1

4}

Affiliations

¹ Beijing Key Laboratory of Microstructure and Properties of Solids, Institute of Microstructure and Property of Advanced Materials, Faculty of Materials and Manufacturing, Beijing University of Technology, Beijing, 100124, China.
² Beijing International Science and Technology, Cooperation Base of Antivirus Drug, Department of Environment and Life Science, Beijing University of Technology, Beijing, 100124, China.
³ Department of Materials Science and Engineering and State Key Laboratory of Silicon Materials, Zhejiang University, Hangzhou, 310058, China.
⁴ Beijing Key Laboratory of Microstructure and Properties of Solids, Institute of Microstructure and Property of Advanced Materials, Beijing International Science and Technology, Cooperation Base of Antivirus Drug, Department of Environment and Life Science, State Key Laboratory of Silicon Materials, Beijing, 100005, Zhejiang 310058, China.
⁵ Beijing International Science and Technology, Cooperation Base of Antivirus Drug, Department of Environment and Life Science, Beijing University of Technology, Beijing, 100124, China. shengwang@bjut.edu.cn.
⁶ Beijing Key Laboratory of Microstructure and Properties of Solids, Institute of Microstructure and Property of Advanced Materials, Beijing International Science and Technology, Cooperation Base of Antivirus Drug, Department of Environment and Life Science, State Key Laboratory of Silicon Materials, Beijing, 100005, Zhejiang 310058, China. shengwang@bjut.edu.cn.

Abstract

Background: Combinatorial immunotherapy strategies for enhancing the responsiveness of immune system have shown great promise for cancer therapy. Engineered nanoformulation incorporated toll-like receptor (TLR) 9 agonist CpG ODN has shown more positive results in suppressing tumor growth and can significantly enhance other immunotherapy activity with combinatorial effects due to the innate and adaptive immunostimulatory effects of CpG.

Results: In the present work, protamine sulfate (PS) and carboxymethyl β-glucan (CMG) were used as nanomaterials to form nanoparticles through a self-assembly approach for CpG ODN encapsulation to generate CpG ODN-loaded nano-adjuvant (CNPs), which was subsequently mixed with the mixture of mouse melanoma-derived antigens of tumor cell lysates (TCL) and neoantigens to develop vaccine for anti-tumor immunotherapy. The obtained results showed that CNPs was able to effectively deliver CpG ODN into murine bone marrow-derived dendritic cells (DC) in vitro, and remarkably stimulate the maturation of DC cells with proinflammatory cytokine secretion. In addition, in vivo analysis showed that CNPs enhanced anti-tumor activity of PD1 antibody and CNPs-adjuvanted vaccine based on the mixture antigens of melanoma TCL and melanoma-specific neoantigen could not only induce anti-melanoma cellular immune responses, but also elicit melanoma specific humoral immune responses, which significantly inhibited xenograft tumor growth. Furthermore, CD16 CAR-T cells were generated by expressing CD16-CAR in CD3⁺CD8⁺ murine T cells.

Conclusion: Our results eventually showed that anti-melanoma antibodies induced by CNPs-adjuvanted TCL vaccines were able to collaborate with CD16-CAR-T cells to generate an enhanced targeted anti-tumor effects through ADCC (antibody dependent cell cytotoxicity) approach. CD16 CAR-T cells has thus a great potential to be an universal promising strategy targeting on solid tumor synergistic immunotherapy via co-operation with TCL-based vaccine.

Keywords: CD16; CpG ODN; Immunotherapy; Neoantigen; Vaccine.

MeSH terms

Adjuvants, Immunologic / pharmacology
Animals
Antibody-Dependent Cell Cytotoxicity
Antigens, Neoplasm
Humans
Mice
Mice, Inbred C57BL
Nanoparticles*
Neoplasms*
Oligodeoxyribonucleotides / pharmacology
Vaccines*

Substances

Adjuvants, Immunologic
Antigens, Neoplasm
Oligodeoxyribonucleotides
Vaccines

Abstract

MeSH terms

Substances

Grants and funding