Mp65-19 a Murine Model of Ox-40 and Pd-1 Immunotherapy in Combination With Vascular Target Photodynamic Therapy (vtp) on Urothelial Cancer Treatment
Year: 2018
Type: article
Abstract: INTRODUCTION AND OBJECTIVES: WST11-VTP creates a strong antitumor immune reaction by exposing tumor antigens and trigging some systemic immune response.We postulated that the combination of VTP ablation with check point immune modulators OX-40 and PD-1 could improve local tumor control and survival in a murine urothelial cancer model.METHODS: 65 Black6 immunocompetent mice were Subcutaneous injected with Luciferase MB-49 cells in the right flank.After 14 days the tumors were measured and image performed.8 groups were created with similar tumors dimension: controls (5), PD1 (5), OX40 (5), PD1þOX40 (10), VTP (10), VTPþPD1 (10), VTPþOX40 (10), VTPþPD1þOX40 (10).VTP was performed on day 15 and the antibodies on the day after following this schedule: single dose of OX40 and 6 doses of PD1 (one every 3 days).IVIS Spectrum images and tumor measurements were done once week until 90 days.The experiment was repeated twice.Immunohistochemistry and Flow cytometry of the tumor were done in 2 different endpoints for lymphocytes expression: 3 days and 7 days after VTP procedure.Statistical analysis was done using the GraphPadâ Prism 7 software RESULTS: After 90 days, the survival rate in the VTPs groups was 12.5%, 22.2%, 33% and 66% for VTP þ OX40, VTP þ PD1, VTP and VTPþPD1þOX40 (VPO) respectively (p<0.001).One mouse (10%) from OX40þPD1 combination survived whereas all mice from the others group without VTP died before 60 days (no statistical difference compared to control group).Only VPO group and OX40þPD1 group did not present lung metastasis in IVIS image during the study (p<0.001).Immunohistochemistry (IHC) showed statistical difference comparing CD4 and CD8 expression in VPO and OX40þPD1 with the others group (p<0.001),especially on day 7 after VTP.Similar results were demonstrated by flow cytometry on day 7: VPO increased fourfold in CD4, six fold in CD8 (Graph 1) and 15 times more in CD4þKi67 expression compare to VTP alone (p<0.001).CONCLUSIONS: Ox-40 þ PD-1 immunotherapy in combination with VTP improves local tumor control and survival in MB-49 cell line model.The 2 different pathways combination seems rationale and encouraging approach in VTP treatment of urothelial cancer
Source: The Journal of Urology
Authors: Ricardo Alvim, Souhil Lebdai, Alexander Somma, Karan Nagar, Christopher Hughes, Sebastien Monette, Petrina Georgala, Rui Gardner, Kwanghee Kim, Jonathan Coleman
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2795796462