Abstract 2007: Use of an anti-IL-10 antibody to improve Mifamurtide efficacy on aggressive osteosarcoma cells

Abstract

Osteosarcoma is a primary malignant bone tumor highly aggressive and metastasizing, composed of mesenchymal cells producing osteoid and immature matrix. Osteosarcoma is the most frequent bone tumor and it mainly affects children and adolescents. The main treatment option is a combination of surgery and chemotherapy. Research into new therapeutic strategies to improve the quality of life of patients is currently underway. The development of the anti-tumor immunostimulant drug Mifamurtide is part of this research. There are very conflicting opinions on the therapeutic validity of this drug. Therefore, we tested experimentally the effectiveness of Mifamurtide in three cell lines of osteosarcoma (MG-63, HOS, 143B) with different grades of malignancy, grown in co-culture with macrophage to allow the correct internalization of the drug. Through in vitro experiments, we analyzed the effects of Mifamurtide on tumor cell viability, on cellular signaling pathway and on macrophage polarization. Results show that Mifamurtide loses its effectiveness as the tumor malignity increases. The most aggressive tumor cells are not affected by the therapy, probably because they implement methods of resistance to apoptosis. Furthermore, they would be able to affect the tumor microenvironment to their own advantage. To better understand Mifamurtide impact on tumor microenvironment, we also performed a cytokine assay on the culture medium in which the cells grew. The most significant results were identified in the interleukine-10 (IL-10): IL-10 is expressed in higher quantities in the highest-grade osteosarcoma cells. This anti-inflammatory cytokine can inhibit the synthesis of pro-inflammatory cytokine and suppresses the antigen presentation capacity of APC cells. This allows cancer cells to evade immune surveillance mechanisms. In vivo and in vitro results show that the synergic use of an anti-IL-10 antibody in combination with Mifamurtide can improve its efficacy. Here, we provide experimental evidence that the addition of an anti-IL-10 antibody to Mifamurtide causes a significant death rate in more aggressive osteosarcoma cells and lower metastasis, compared to Mifamurtide only. In conclusion, considering our data, it could be proposed a new treatment protocol for metastatic osteosarcoma that includes the use of an anti-IL10 antibody integrated with the administration of Mifamurtide to increase its effectiveness in this clinical context. Citation Format: Nicoletta Nastasi, Angela Subbiani, Maria Letizia Taddei, Lucia Scala, Angela Tamburini, Claudio Favre, Maura Calvani. Use of an anti-IL-10 antibody to improve Mifamurtide efficacy on aggressive osteosarcoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2007.