On October 19, 2022 INmune Bio, Inc. (NASDAQ: INMB) (the "Company"), a clinical-stage immunology company focused on developing treatments that harness the patient’s innate immune system to fight disease, reported that positive solid tumor data in multiple cancer lines resistant to NK killing that can be overcome with administration of INKmune (Press release, INmune Bio, OCT 19, 2022, View Source [SID1234622186]).
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Solid tumors represent approximately 90% of adult human cancers while the majority of cell therapies focus on the 10% of cancers that are hematologic tumors, or "liquid tumors." The current data provides insights into why the Company believes that INKmune arms Natural Killer (NK) to override immunosuppression and hypoxia in an active Tumor Microenvironment (TME) to kill solid tumors.
The interaction of the TME with cancer cells and immune cells can drive tumor progression and prevent many cell therapies from being effective. These complex interactions should be considered when designing cell therapies to treat solid tumors. In solid tumors, the TME is hostile to cell therapies because of (i) the presence of immunosuppressive immunoregulatory cells, and (ii) the low levels of oxygen (hypoxia). A cell therapy must operate in this hostile environment to successfully treat solid tumors,
INKmune converts patient’s normal resting NK (rNK) cells into potent memory-like NK cells that target solid tumors directly, even in the presence of immunosuppressive immunoregulatory cells and hypoxia associated with the TME. The Company’s pre-clinical data show that INKmune primes NK cells from patients and from healthy donors to lyse NK-resistant ovarian (CaOva), prostate (CaPros), renal (RCC) and nasopharyngeal (NPC) cancer cells. When compared to rNK cells, which are normal NK cells from healthy donors or patients before treatment with INKmune, the INKmune primed NK cells demonstrated enhanced ability to kill these resistant tumor cell lines.
The value in the tables is percent of tumor cells killed. For instance, in the table below looking at laboratory assay using healthy donor NK cells killing of a prostate cell line called DU145, resting NK cells that have not been primed with INKmune kill fewer than 4% of the DU145 cells in 4 hours. INKmune primed NK cells kill approximately 66% of DU145 cells in the same amount of time. Negative values mean that the tumor cells grew faster than the NK cells could kill them.
The Company identified more than1,500 proteins that are upregulated in NK cells following INKmune priming and subsequent analysis compared them to NK cells primed with a cytokine cocktail of IL-12, IL-15 and IL-18. Of the 250 most upregulated proteins, 141 are completely unique to INKmune priming and are not upregulated by the cytokines IL-12, IL-15 and IL-18. Many of these unique proteins are involved in cell survival and the enhanced metabolism likely to protect INKmune primed NK cells in the TME. "We believe the upregulation of key proteins associated with enhanced metabolic fitness and mitochondrial repair in the NK cells are critical for NK survival in the TME of solid tumors," said Dr. Mark Lowdell, the Company’s CSO.
There remains an unmet need for novel treatments in prostate, renal and nasopharyngeal cancers. The number of patients who could benefit exceeds 4 million annually in the US alone. These data support INmune Bio’s decision to transition INKmune trials into the treatment of solid tumors.
The company presented the data at the Innate Killer Summit Europe on October 19th. A video of the presentation will be uploaded to the company’s website by Wednesday next week.
About INKmune
INKmune is a proprietary pharmaceutical-grade, replication-incompetent human tumor cell line which conjugates to resting NK cells and delivers multiple, essential priming signals akin to treatment with at least three cytokines in combination. INKmune is stable at -80oC and is delivered by a simple IV infusion. The INKmune:NK interaction ligates multiple activating and co-stimulatory molecules on the NK cell and enhances its avidity of binding to tumor cells; notably those resistant to normal NK-mediated lysis. Tumor-primed NK (TpNK) cells can lyse a wide variety of NK-resistant tumors including leukemias, lymphomas, myeloma, ovarian cancer, breast cancer and the solid tumors shown above.