Intratumoral immunotherapy of murine pheochromocytoma shows no age-dependent differences in its efficacy

Front Endocrinol (Lausanne). 2023 May 8:14:1030412. doi: 10.3389/fendo.2023.1030412. eCollection 2023.

Abstract

Cancer immunotherapy has shown remarkable clinical progress in recent years. Although age is one of the biggest leading risk factors for cancer development and older adults represent a majority of cancer patients, only a few new cancer immunotherapeutic interventions have been preclinically tested in aged animals. Thus, the lack of preclinical studies focused on age-dependent effect during cancer immunotherapy could lead to different therapeutic outcomes in young and aged animals and future modifications of human clinical trials. Here, we compare the efficacy of previously developed and tested intratumoral immunotherapy, based on the combination of polysaccharide mannan, toll-like receptor ligands, and anti-CD40 antibody (MBTA immunotherapy), in young (6 weeks) and aged (71 weeks) mice bearing experimental pheochromocytoma (PHEO). The presented results point out that despite faster growth of PHEO in aged mice MBTA intratumoral immunotherapy is effective approach without age dependence and could be one of the possible therapeutic interventions to enhance immune response to pheochromocytoma and perhaps other tumor types in aged and young hosts.

Keywords: TLR ligands; age; anti-CD40 antibody; intratumoral immunotherapy; pancreatic adenocarcinoma; pheochromocytoma.

Publication types

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

MeSH terms

  • Adrenal Gland Neoplasms* / therapy
  • Aged
  • Animals
  • CD40 Antigens
  • Humans
  • Immunotherapy / methods
  • Mice
  • Pheochromocytoma* / therapy
  • Toll-Like Receptors

Substances

  • Toll-Like Receptors
  • CD40 Antigens

Grants and funding

This research was supported by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development and by the Research Support Foundation (Vaduz, Fürstentum, Lichtenstein).