» Articles » PMID: 37180119

Delivering Co-stimulatory Tumor Necrosis Factor Receptor Agonism for Cancer Immunotherapy: Past, Current and Future Perspectives

Overview
Journal Front Immunol
Date 2023 May 14
PMID 37180119
Authors
Affiliations
Soon will be listed here.
Abstract

The tumor necrosis factor superfamily (TNFSF) and their receptors (TNFRSF) are important regulators of the immune system, mediating proliferation, survival, differentiation, and function of immune cells. As a result, their targeting for immunotherapy is attractive, although to date, under-exploited. In this review we discuss the importance of co-stimulatory members of the TNFRSF in optimal immune response generation, the rationale behind targeting these receptors for immunotherapy, the success of targeting them in pre-clinical studies and the challenges in translating this success into the clinic. The efficacy and limitations of the currently available agents are discussed alongside the development of next generation immunostimulatory agents designed to overcome current issues, and capitalize on this receptor class to deliver potent, durable and safe drugs for patients.

Citing Articles

MD Simulation Reveals a Trimerization-Enhanced Interaction of CD137L with CD137.

Wang H, Wu J, Fang Y, Li Q Int J Mol Sci. 2025; 26(5).

PMID: 40076530 PMC: 11899465. DOI: 10.3390/ijms26051903.


First-in-human, phase 1 dose escalation study of SL-279252, a hexameric PD1-Fc-OX40L fusion protein, in patients with advanced solid tumors and lymphoma.

Johnson M, Hong D, Brana I, Schoffski P, Galvao V, Rangwala F Invest New Drugs. 2025; .

PMID: 40042547 DOI: 10.1007/s10637-025-01518-7.


Generation and characterization of OX40-ligand fusion protein that agonizes OX40 on T-Lymphocytes.

Sato A, Nagai H, Suzuki A, Ito A, Matsuyama S, Shibui N Front Immunol. 2025; 15:1473815.

PMID: 39867912 PMC: 11757143. DOI: 10.3389/fimmu.2024.1473815.


Targeting the TNF and TNFR superfamilies in autoimmune disease and cancer.

Croft M, Salek-Ardakani S, Ware C Nat Rev Drug Discov. 2024; 23(12):939-961.

PMID: 39448880 DOI: 10.1038/s41573-024-01053-9.


Exploring miRNA therapies and gut microbiome-enhanced CAR-T cells: advancing frontiers in glioblastoma stem cell targeting.

Sandhanam K, Tamilanban T, Bhattacharjee B, Manasa K Naunyn Schmiedebergs Arch Pharmacol. 2024; .

PMID: 39382681 DOI: 10.1007/s00210-024-03479-9.


References
1.
Richman L, Vonderheide R . Role of crosslinking for agonistic CD40 monoclonal antibodies as immune therapy of cancer. Cancer Immunol Res. 2014; 2(1):19-26. PMC: 3883444. DOI: 10.1158/2326-6066.CIR-13-0152. View

2.
Nikolopoulos G, Smith C, Brookes S, El-Asrag M, Brown C, Patel A . New missense variants in RELT causing hypomineralised amelogenesis imperfecta. Clin Genet. 2020; 97(5):688-695. PMC: 7216828. DOI: 10.1111/cge.13721. View

3.
Gardner A, Ruffell B . Dendritic Cells and Cancer Immunity. Trends Immunol. 2016; 37(12):855-865. PMC: 5135568. DOI: 10.1016/j.it.2016.09.006. View

4.
Qamar N, Fuleihan R . The hyper IgM syndromes. Clin Rev Allergy Immunol. 2013; 46(2):120-30. DOI: 10.1007/s12016-013-8378-7. View

5.
Durandy A, Revy P, Fischer A . Human models of inherited immunoglobulin class switch recombination and somatic hypermutation defects (hyper-IgM syndromes). Adv Immunol. 2004; 82:295-330. DOI: 10.1016/S0065-2776(04)82007-8. View