Login to Access Video or Poster Abstract: MP98-09
Sources of Funding: Duke University

Introduction

We developed a novel treatment for localized and metastatic bladder cancer comprised of gold nanoparticle-based photothermal therapy and immunotherapy (SYMPHONY). We demonstrate that it effectively ablates primary tumors, destroys metastases abscopally, and induces potent anti-tumor immunity.

Methods

MB49 murine bladder cancer cells were injected into the bilateral flanks of C57BL/6 mice and grown until 100 mm3 in size. PEG-functionalized gold nanostars, developed and manufactured by our team, were administered intravenously. A 808-nm laser (0.6 W/cm2) was used to trigger plasmonic heat production from the gold nanostars in the left flank 24 hours after injection, while the contralateral flank was left untreated. Anti-PD-L1 antibody immunotherapy was co-administered intraperitoneally and repeated q3days. Mice were assessed for ipsilateral and contralateral tumor response and survival. Flow cytometry, multiplex cytokine profiling, and T cell receptor sequencing were used to characterize the immune response. Mice achieving a complete response were rechallenged with an additional injection of MB49 tumor cells 90 days later.

Results

Gold nanostar-mediated phototherapy alone completely ablated ipsilateral tumors in 4/5 of mice (pT0 at necropsy) but contralateral tumors grew and all 5 mice required sacrifice within 14 days. Anti-PD-L1 therapy alone slowed tumor growth in 3/5 mice, but tumors rapidly began growing again and 5/5 mice required sacrifice by 45 days. Combined treatment (i.e. SYMPHONY) ablated 5/5 ipsilateral tumors and resulted in partial (3/5) and complete responses (2/5) of untreated contralateral tumors, demonstrating a strong abscopal effect. After 90 days of follow-up, the two mice achieving a complete response with SYMPHONY were rechallenged with MB49 and neither developed a tumor over the ensuing 4 weeks indicating strong and effective immune memory. Flow cytometry showed CD4 and CD8 T cell proliferation, decreased myeloid derived suppressor cells, and increased IL2 with SYMPHONY.

Conclusions

SYMPHONY treatment resulted not only in effective ablation of primary tumors but also in immune-mediated abscopal destruction of untreated distant tumors. Strong and permanent anti-tumor immunity developed in some mice, indicating that with further optimization, SYMPHONY may be able to cure more advanced bladder cancers.

Funding

Duke University