Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) for the Treatment of Unresectable and Metastatic Cancers

Abstract

Metastatic spread is the mechanism in more than 90 percent of cancer deaths and current therapeutic options, such as systemic chemotherapy, are often ineffective. Here we provide a proof of principle for a novel two-pronged modality referred to as Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) having the potential to safely eradicate both primary tumors and distant metastatic foci. Using a combination of immune-checkpoint inhibition and plasmonic gold nanostar (GNS)–mediated photothermal therapy, we were able to achieve complete eradication of primary treated tumors and distant untreated tumors in some mice implanted with the MB49 bladder cancer cells. Delayed rechallenge with MB49 cancer cells injection in mice that appeared cured by SYMPHONY did not lead to new tumor formation after 60 days observation, indicating that SYMPHONY treatment induced effective long-lasting immunity against MB49 cancer cells.

What Potential Does plasmonics-amplified Synergistic Immuno Photothermal Nanotherapy have for Treatment of cancer?

“…However, checkpoint-based drugs work only for a limited number of patients and can become ineffective with time. Broadening and stabilizing the effect of PD-L1/PD1 inhibitors can be achieved with nanoparticle-mediated synergistic thermal therapies [21]. Our results have indicated that by using a combination of immune-checkpoint inhibition and gold nanostar (GNS)-mediated photothermal therapy, it is possible to achieve complete eradication of primary treated tumors as well as distant untreated tumors tumors and induce long-term anti-cancer immunity in mice implanted with the MB49 bladder cancer cell line.…”

“…Recently, we demonstrated that the use of plasmonic gold nanostars (GNS) in combination with immunotherapy -a treatment we referred to as Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) -can dramatically enhance the efficacy of immunotherapy. Remarkably, we have found that SYMPHONY not only eradicates primary 'treated' tumors but also has resulted in the immune-mediated destruction of distant 'untreated' metastatic tumors [21]. This abscopal effect occurred uniquely when nanoparticle-mediated photothermal heating of tumors was used in combination with immunotherapy.…”

“…Similarly, plasmonic nanoparticles such as GNS operate as nano-activators of the immune system in two ways [21]. First, following ablation, dying tumor cells release tumor-specific antigens, damage-associated molecular pattern molecules (DAMPs), and heat shock proteins.…”

Nanoparticle‐based photothermal and photodynamic immunotherapy for tumor treatment

“…However, numerous studies have recently revealed that the inhibitory effect by PTT alone is insufficient on primary tumor growth, even more so on distant metastatic tumors. 66 Additional details and other existing combination therapies are listed in Table 1. Under certain conditions, tumor cells appear to be tolerant to or even dependent on the immune system.…”

“…These results confirm that this combination therapy is an effective treatment of in situ and distant tumors by heat ablation following immune activation and relief of tumor defense. 66 Additional details and other existing combination therapies are listed in Table 1. Anti-CTLA-4 monotherapy can induce the expression of PD-L1 in a tumor micro-environment, which is expected to hinder T cell-induced antitumor immunity.…”