Rescue of dendritic cells from glycolysis inhibition improves cancer immunotherapy in mice

Sahil Inamdar, Abhirami P. Suresh, Joslyn L. Mangal, Nathan D. Ng, Alison Sundem, Christopher Wu, Kelly Lintecum, Abhirami Thumsi, Taravat Khodaei, Michelle Halim, Nicole Appel, Madhan Mohan Chandra Sekhar Jaggarapu, Arezoo Esrafili, Jordan R. Yaron, Marion Curtis and Abhinav P. Acharya ()
Additional contact information
Sahil Inamdar: Arizona State University
Abhirami P. Suresh: Arizona State University
Joslyn L. Mangal: Arizona State University
Nathan D. Ng: Arizona State University
Alison Sundem: Arizona State University
Christopher Wu: Arizona State University
Kelly Lintecum: Arizona State University
Abhirami Thumsi: Arizona State University
Taravat Khodaei: Arizona State University
Michelle Halim: Arizona State University
Nicole Appel: Arizona State University
Madhan Mohan Chandra Sekhar Jaggarapu: Arizona State University
Arezoo Esrafili: Arizona State University
Jordan R. Yaron: Arizona State University
Marion Curtis: Mayo Clinic
Abhinav P. Acharya: Arizona State University

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: Abstract Inhibition of glycolysis in immune cells and cancer cells diminishes their activity, and thus combining immunotherapies with glycolytic inhibitors is challenging. Herein, a strategy is presented where glycolysis is inhibited in cancer cells using PFK15 (inhibitor of PFKFB3, rate-limiting step in glycolysis), while simultaneously glycolysis and function is rescued in DCs by delivery of fructose-1,6-biphosphate (F16BP, one-step downstream of PFKFB3). To demonstrate the feasibility of this strategy, vaccine formulations are generated using calcium-phosphate chemistry, that incorporate F16BP, poly(IC) as adjuvant, and phosphorylated-TRP2 peptide antigen and tested in challenging and established YUMM1.1 tumours in immunocompetent female mice. Furthermore, to test the versatility of this strategy, adoptive DC therapy is developed with formulations that incorporate F16BP, poly(IC) as adjuvant and mRNA derived from B16F10 cells as antigens in established B16F10 tumours in immunocompetent female mice. F16BP vaccine formulations rescue DCs in vitro and in vivo, significantly improve the survival of mice, and generate cytotoxic T cell (Tc) responses by elevating Tc1 and Tc17 cells within the tumour. Overall, these results demonstrate that rescuing glycolysis of DCs using metabolite-based formulations can be utilized to generate immunotherapy even in the presence of glycolytic inhibitor.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-41016-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41016-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-41016-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().