Abstract C048: Novel master checkpoint Cbl-b siRNA-based adoptive cellular therapy: Superior antitumor efficacy in a syngeneic murine hepatocellular carcinoma Hepa1-6 model following APN401 monotherapy and synergistic effects with anti-PD1
| Autor: | Alexander B. Dohnal, Hannes Muehleisen, Anthony B. El-Khoueiry, Romana Gugenberger, Carlos Becerra, Josef M. Penninger, Karin Drobits, Vincent Chung, Julia Harrauer, Maria Urban, Guenther Lametschwandtner, Isabella Haslinger, Anderson Gaweco, Kathrin Thell |
|---|---|
| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Molecular Cancer Therapeutics. 18:C048-C048 |
| ISSN: | 1538-8514 1535-7163 |
| Popis: | Introduction: The E3 ubiquitin ligase Cbl-b is an intracellular master checkpoint which negatively regulates both adaptive and innate anti-tumor immune responses. Selective targeting of Cbl-b not only induces anti-tumor activity in vivo but also overrides immune regulation by the PD-L1/PD-1 pathway in vitro (2017 Fujiwara et al). Human APN401 is an autologous adoptive cellular therapy of ex vivo Cbl-b-silenced human PBMCs currently in a clinical Phase 1b multiple dose study demonstrating early clinical safety and tolerability in patients with advanced solid tumors. Herein the preclinical Proof of Concept efficacy of murine APN401 immunotherapy is established in the syngeneic mouse hepatocellular carcinoma Hepa1-6 model. Experimental Procedure: Hepa1-6-C57/BL6-tumor bearing mice were treated with murine APN401 ex vivo silenced immune cells with Cbl-b specific siRNA as monotherapy or in combination with anti-PD1 (clone RMP1-14) versus control siRNA. Mice were treated for 14 d starting on D7 after inoculation of Hepa1-6 cells and tumor volume was measured daily. Results: Murine APN401 treatment alone significantly suppressed Hepa1-6 tumor growth by 56% (p Citation Format: Anderson Gaweco, Kathrin Thell, Maria Urban, Julia Harrauer, Isabella Haslinger, Alexander Dohnal, Guenther Lametschwandtner, Karin Drobits, Romana Gugenberger, Hannes Muehleisen, Josef Penninger, Carlos Becerra, Vincent Chung, Anthony El-Khoueiry. Novel master checkpoint Cbl-b siRNA-based adoptive cellular therapy: Superior antitumor efficacy in a syngeneic murine hepatocellular carcinoma Hepa1-6 model following APN401 monotherapy and synergistic effects with anti-PD1 [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr C048. doi:10.1158/1535-7163.TARG-19-C048 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|