The use of anchored agonists of phagocytic receptors for effective cancer immunotherapy

Konference: 2015 XI. Dny diagnostické, prediktivní a experimentální onkologie

Kategorie: Nádorová biologie/imunologie/genetika a buněčná terapie

Téma: Protinádorová léčiva a postupy I

Číslo abstraktu: 013

Autoři: Veronika Caisová; Andra Vieru; Zuzana Kumžáková; Simona Glaserová; Bc. Hana Husníková; Mgr. Nikol Vácová; prof. RNDr. Jan Kopecký, CSc.; RNDr. Jan Ženka (1955-), CSc.

Introduction

The idea of the use of killed microorganisms or their parts for stimulation of immunity and cancer immunotherapy is very old. Our novel approach is based on installation of ligands of phagocytic receptors on tumor cells. Therapeutic effect is further amplified by simultaneous application of TLR agonists. We focused on searching for proper ligands causing strong therapeutic effect and safe for humans.

Materials/methods

For stimulation of phagocytosis we used laminarin, mannan or N-formylmethioninyl-leucyl-phenylalanine covalently bound to tumor cells or attached using hydrophobic anchor. As TLR ligands MPLA, Imiquimod, Resiquimod, POLY I:C, and heat killed Listeria monocytogenes were used. Study was performed using B16-F10 murine melanoma model.

Results and conclusions

Resiquimod proved to be the most suitable TLR agonist. Its combination with mannan covalently bound to tumor cells significantly reduced tumor growth. Addition of POLY I:C and L. monocytogenes caused complete recovery of 83% of mice and protected them against retransplantation of melanoma cells. Combination of soluble TLR agonists and to tumor cells attached ligands stimulating phagocytosis can lead to very efficient cancer treatment.

Datum přednesení příspěvku: 2. 12. 2015