Abstract
Abstract Background: Programmed death ligand 1 (PDL1) is commonly expressed on the surface of many tumor cells, including breast cancer. The activity of tumor infiltrating lymphocytes (TIL) is inhibited by PDL1. Blocking PDL1 with monoclonal antibodies can prevent this immune suppression and enhance anti-tumor activity. Polyinosinic-polycytidylic acid (Poly I:C) is a Toll like receptor 3 (TLR3) agonist which was shown to synergize with anti-PDL1 antibodies in a B16 melanoma model (Celis et. al, Blood 2010). We sought to investigate if synergy could be demonstrated in a murine breast cancer model. Methods: Five week old female BALB/c mice were injected with 3x106 4T1 cells in a mammary fat pad and divided into 4 groups with ten mice/group (PBS control, 200µg anti-PDL1 antibody (10F.9G2 Bioxcell) D1,5 IP, 50µg Poly I:C (Invivogen) D1,6,11,16 IV, anti-PDL1+Poly I:C). Treatment started when tumors were palpable and measured twice weekly. The mice were sacrificed 20 days later with tumors, spleens, and lymph nodes harvested. Tumors were measured twice weekly. All experiments were carried out under approved IACUC #4277R per institutional guidelines. Statistical analysis performed using Prism Graphpad. Results: Mean tumor measurements (mm2) at day 20 for control=207.5, anti-PDL1=188.5, Poly I:C=182.6, anti-PDL1+Poly I:C=149.4. Two way ANOVA was statistically significant at p<.0001. Mean tumor weight (gm) at day 20 of anti-PDL1+Poly I:C=.99 vs control=1.23 p=.002 using t test. Conclusions: The combination of anti-PDL1 and Poly I:C TLR3 agonist demonstrates improved anti-tumor activity against established 4T1 orthotopic murine breast tumors compared to control or either agent alone. Characterization of TIL infiltrates in tumor specimens and immune activation in harvested lymphocytes is ongoing and will be presented. This data provides preliminary evidence supporting continued investigation of the combination of PDL1 and Poly I:C immunotherapy for breast cancer. Citation Format: Hatem Soliman, Ashley R. Nelson. Combination immunotherapy with PD-L1 blockade and Poly I:C in a murine breast cancer model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5018. doi:10.1158/1538-7445.AM2014-5018
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
