NPS delivery can achieve “complete small (3 to 5 mm) local tumor remission without recurrence” in animal mouse and rat models, Dr Guo said.
Dr Guo was lead author of a recently published study of NPS induction of immune responses against breast cancers in a mouse model, funded in part by Pulse Biosciences.6 A single NPS treatment triggered “complete regression” of metastatic 4T1-Luc mouse mammary carcinoma model tumors, and prevented distant organ metastasis, the researchers reported.6
“The survival of those animals was significantly prolonged,” Dr Guo said. “Importantly, even when complete tumor regression does not occur, locally treated tumors grow more slowly.”
While this and other preclinical experiments suggest that NPS can destroy tumors and inhibit secondary tumor growth, the different ways it might do so are not yet completely understood.7,8
One mechanism of action for NPS is induction of apoptosis, which renders it a non-thermal ablation modality.4 NPS followed by hyperthermia (chilling with ice) appears to be cytotoxic because of induced apoptosis.9 But NPS also appears to stimulate immune attacks on tumor cells.6-8
“NPS influences or controls cell behaviors [and] fate by multiple actions,” said Dr Guo. “Mammalian tumor cells exposed to NPS are indicated to have permeabilization of both plasma and organelle membranes, allowing entry of disruptive small ions, disturbances of intracellular vesicles, release of calcium from endoplasmic reticulum stores, and loss of mitochondrial membrane potential — all with the potential to cause tumor cell death.”
Most previously published research on NPS assessed its potential utility for local tumor ablation. But Dr Guo’s team is investigating its effects on antitumor immune response.
“Potent immune responses are induced by NPS treatment,” Dr Guo said. “Major responsive cells, both CD4+ and CD8+ T cells, are significantly increased and show cytotoxic function by release of interferon-gamma. After NPS treatment, all tumor-free animals (100% or 11/11) reject secondary live tumor challenge.”
That suggests a “vaccine-like” protection effect.
“Mouse breast tumor cells treated with NPS release several damage-associated molecular patterns (DAMPs), known as immunogenic cell death markers, that can activate dendritic cells (DCs) in vitro and presumably in vivo,” Dr Guo said. “We show that DCs can be activated directly with non-lethal doses of NPS.”