Mechanism of Action

Localized Cell Death

Due to the use of a novel cell penetration enhancing agent, INT230-6 treatment has demonstrated strong efficacy in animals having large tumors and clinical benefit in humans. Our in vivo data shows that INT230-6 thoroughly saturates and kills injected tumors. Previously presented biopsy data demonstrated substantial reduction of viable tumor cells after 2 doses, and influx of CD4 and CD8 T cells.

Comparison of dispersion of aqueous drug solutions containing -((2-hydroxybenzoyl)amino) octanoate (SHAO) with India Ink compared to aqueous vehicle with drug (cis) with Ink alone in BxPc3-luc2 pancreatic murine tumor xenografts. Paraffin blocks were made from the injected tumors. Caliper measurements of the longest axis of the stained region were taken to estimate the degree of ink dispersion (INT230-6: mean 8.25 mm vs. drug alone: 2.8 mm p < 0.0002).

System-wide Immune Response

When tumors are injected with our drug, the cancer cells die; however, the cell membranes remain intact, making cancer more recognizable to the immune system.  Essentially, the “soft” manner by which the tumor dies converts the patient’s tumor into a personalized mass of high-quality antigen. Once the patient’s cancer is recognized by the immune system, there can be a whole-body attack against the cancer. Our research, which was published in collaboration with the National Cancer Institute, has shown that the immune response is amplified significantly when Intensity’s drugs are dosed in combination with immunotherapies such as anti-PD-1 and anti-CTLA-4 antibodies. In addition, data suggest that the immunotherapy, when dosed in combination with INT230-6, may be less likely to attack healthy cells.

IHC analysis of Colon-26 tumors untreated and INT230-6-treated tumors ~10 days post dose. 

Representative images (40x magnification) of IHC staining for CD4+ (T-cells), F4/80 (macrophages), CD335 (natural killer cells), and CD11c (dendritic cells). In general, the staining appeared more evident in the INT230-6-treated tumors, particularly toward the more necrotic areas.  Int. J. Mol. Sci. 2020, 21, 4493