Albumin/vaccine nanocomplexes that assemble in vivo for combination cancer immunotherapy

Guizhi Zhu; Geoffrey M Lynn; Orit Jacobson; Kai Chen; Yi Liu; Huimin Zhang; Ying Ma; Fuwu Zhang; Rui Tian; Qianqian Ni; Siyuan Cheng; Zhantong Wang; Nan Lu; Bryant C Yung; Zhe Wang; Lixin Lang; Xiao Fu; Albert Jin; Ido D Weiss; Harshad Vishwasrao; Gang Niu; Hari Shroff; Dennis M Klinman; Robert A Seder; Xiaoyuan Chen

doi:10.1038/s41467-017-02191-y

Albumin/vaccine nanocomplexes that assemble in vivo for combination cancer immunotherapy

Nat Commun. 2017 Dec 5;8(1):1954. doi: 10.1038/s41467-017-02191-y.

Authors

Guizhi Zhu¹, Geoffrey M Lynn², Orit Jacobson¹, Kai Chen³, Yi Liu^{1

4}, Huimin Zhang¹, Ying Ma¹, Fuwu Zhang¹, Rui Tian¹, Qianqian Ni¹, Siyuan Cheng¹, Zhantong Wang^{1

5}, Nan Lu¹, Bryant C Yung¹, Zhe Wang¹, Lixin Lang¹, Xiao Fu⁶, Albert Jin⁶, Ido D Weiss⁷, Harshad Vishwasrao⁸, Gang Niu¹, Hari Shroff^{8

9}, Dennis M Klinman¹⁰, Robert A Seder², Xiaoyuan Chen¹¹

Affiliations

¹ Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
² Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD, 20892, USA.
³ Molecular Imaging Center, Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
⁴ School of Engineering, China Pharmaceutical University, Nanjing, 210009, China.
⁵ State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
⁶ Laboratory of Cellular Imaging and Macromolecular Biophysics, NIBIB, NIH, Bethesda, MD, 20892, USA.
⁷ Laboratory of Molecular Immunology, NIAID, NIH, Bethesda, MD, 20892, USA.
⁸ Advanced Imaging and Microscopy Resource, National Institutes of Health, Bethesda, 20892, MD, USA.
⁹ Section on High Resolution Optical Imaging, NIBIB, NIH, Bethesda, MD, 20892, USA.
¹⁰ Cancer and Inflammation Program, National Cancer Institute, Frederick, MD, 21702, USA.
¹¹ Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, MD, 20892, USA. shawn.chen@nih.gov.

Abstract

Subunit vaccines have been investigated in over 1000 clinical trials of cancer immunotherapy, but have shown limited efficacy. Nanovaccines may improve efficacy but have rarely been clinically translated. By conjugating molecular vaccines with Evans blue (EB) into albumin-binding vaccines (AlbiVax), here we develop clinically promising albumin/AlbiVax nanocomplexes that self-assemble in vivo from AlbiVax and endogenous albumin for efficient vaccine delivery and potent cancer immunotherapy. PET pharmacoimaging, super-resolution microscopies, and flow cytometry reveal almost 100-fold more efficient co-delivery of CpG and antigens (Ags) to lymph nodes (LNs) by albumin/AlbiVax than benchmark incomplete Freund's adjuvant (IFA). Albumin/AlbiVax elicits ~10 times more frequent peripheral antigen-specific CD8⁺ cytotoxic T lymphocytes with immune memory than IFA-emulsifying vaccines. Albumin/AlbiVax specifically inhibits progression of established primary or metastatic EG7.OVA, B16F10, and MC38 tumors; combination with anti-PD-1 and/or Abraxane further potentiates immunotherapy and eradicates most MC38 tumors. Albumin/AlbiVax nanocomplexes are thus a robust platform for combination cancer immunotherapy.

Publication types

Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic / pharmacology
Albumin-Bound Paclitaxel / pharmacology
Albumins
Animals
Antigens, Neoplasm / immunology
Antineoplastic Agents / pharmacology
Antineoplastic Agents, Immunological / pharmacology
Cancer Vaccines / administration & dosage
Cancer Vaccines / immunology
Cancer Vaccines / pharmacology*
Cell Line, Tumor
Drug Delivery Systems
Freund's Adjuvant / pharmacology
Immunotherapy
Lipids / pharmacology
Lymph Nodes / drug effects*
Lymph Nodes / pathology
Melanoma, Experimental / pathology*
Mice
Molecular Docking Simulation
Nanostructures
Positron-Emission Tomography
T-Lymphocytes, Cytotoxic / drug effects*

Substances

Adjuvants, Immunologic
Albumin-Bound Paclitaxel
Albumins
Antigens, Neoplasm
Antineoplastic Agents
Antineoplastic Agents, Immunological
Cancer Vaccines
Lipids
incomplete Freund's adjuvant
Freund's Adjuvant

Grants and funding

T32 GM007309/GM/NIGMS NIH HHS/United States