Title (eng)

Boosting the anti-tumor activity of natural killer cells by caripe 8 - A Carapichea ipecacuanha isolated cyclotide

Author

Julia List   University of Veterinary Medicine Vienna

Roland Hellinger   Medical University of Vienna

Dagmar Gotthardt   University of Veterinary Medicine Vienna

Eva-M. Putz   University of Veterinary Medicine Vienna

Petra Kudweis   University of Veterinary Medicine Vienna

Heidi A. Neubauer   University of Veterinary Medicine Vienna

Sonja Marinovic   Rudjer Boskovic Institute

Sophie Huszarek   University of Veterinary Medicine Vienna

Jasmin Gattringer   Medical University of Vienna

Publishing

Elsevier

Description (eng)

Cyclotides are head-to-tail cyclized peptides with a unique cystine-knot motif. Their structure provides exceptional resistance against enzymatic, chemical, or thermal degradation compared to other peptides. Peptide-based therapeutics promise high specificity, selectivity and lower immunogenicity, making them safer alternatives to small molecules or large biologicals. Cyclotides were researched due to their anti-cancer properties by inducing apoptosis in tumor cells in the past, but the impact of cyclotides on cytotoxic immune cells was poorly studied. Natural Killer (NK) cells are cytotoxic innate lymphoid cells and play an important role in the defense against infected, stressed and transformed cells. NK cells do not need prior sensitization and act in an antigen independent manner, holding promising potential in the field of immunotherapy. To investigate the effect of immunomodulatory cyclotides on NK cells, we evaluated several peptide-enriched plant extracts on NK cell mediated cytotoxicity. We observed that the extract samples derived from Carapichea ipecacuanha (Brot.) L. Andersson augments the killing potential
of mouse NK cells against different tumor targets in vitro. Subsequent isolation of cyclotides from C. ipecacuanha extracts led to the identification of a primary candidate that enhances cytotoxicity of both mouse and human NK cells. The augmented killing is facilitated by the increased degranulation capacity of NK cells. In addition, we noted a direct toxic effect of caripe 8 on tumor cells, suggesting a dual therapeutic potential in cancer treatment. This study offers novel insights how natural peptides can influence NK cell cytotoxicity. These pre-clinical findings hold significant promise for advancing current immunotherapeutic approaches.

Object languages

English

Date

2024

Rights

This work is licensed under a
CC BY 4.0 - Creative Commons Attribution 4.0 International License.

CC BY 4.0 International

http://creativecommons.org/licenses/by/4.0/

Classification

NK Cells; Anti-Tumor Activity; Cyclotide; Plant-Derived Peptide; Carapichea Ipecacuanha

Member of the Collection(s) (1)