On November 7, 2023 ImmunityBio, Inc. (NASDAQ: IBRX), a clinical-stage immunotherapy company, reported new data showing that the company’s Memory Cytokine-Enriched Natural Killer cells (M-ceNK) may provide benefit to patients with small cell lung cancer and patients with other types of neuroendocrine tumors (Press release, ImmunityBio, NOV 7, 2023, View Source [SID1234637142]). Findings from the study titled "Characterization of the anti-tumor activity of memory cytokine enriched NK cells (M-ceNK) against tumors with neuroendocrine features" were presented by Kristen Fousek, Ph.D., Research Fellow with the Center for Immuno-Oncology of the National Institutes of Health’s National Cancer Institute (NCI) in a poster session (Abstract #358) at the annual meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) in San Diego, November 4, 2023.
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Small cell lung cancer (SCLC) is an aggressive neuroendocrine (NE) carcinoma and has few treatment options. Although immune checkpoint blockade (ICB) is approved in combination with chemotherapy in extensive stage disease, only a subset of patients experience an improvement in overall survival. Studies suggest that a lack of response to ICB is partially attributable to low expression of MHC-class I. Recently, an NCI research group (Fousek et al., 2023) reported that the lack of MHC-class I can be leveraged to enable targeting by NK cells stimulated with ImmunityBio’s IL-15 cytokine superagonist N-803. These findings led researchers to hypothesize that M-ceNK cells may be effective in targeting SCLC.
In the new study, the killing capacity of M-ceNK cells was assessed in four SCLC cell lines representing the major molecular subtypes. M-ceNK cells, generated from cells from several healthy donors, were found to express high levels of activating receptors and low levels of inhibitory receptors, as well as elevated IFN-γ and granzyme B production – all of which are important for anti-tumor activity. The M-ceNK cells were highly cytotoxic against all types of SCLC models, as well as against prostate neuroendocrine cancer. Overall, the study revealed the potential for M-ceNK-based approaches for the treatment of NE tumors, including all molecular subtypes of SCLC and supports future studies in other tumor types that are unresponsive to ICB.
"These results are further evidence of the potential of M-ceNK therapy as a new immunotherapy approach for treating cancers that do not respond to immune checkpoint blockade, the current standard of care," said Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer at ImmunityBio. "We are encouraged by the data coming out of this study and we look forward to assessing the potential for M-ceNK therapy in other tumor types."
About M-ceNK
Memory-like cytokine-enhanced natural killer (M-ceNK cells are a unique set of white blood cells (lymphocytes) that are first collected from individual patients (autologous cells) then differentiated into the specialized NK cells with enhanced anti-cancer function by brief pre-activation with interleukin-12 (IL-12), IL-15, and IL-18. These cells are characterized by their unique cell-surface marker profile and enhanced responses to cytokine re-stimulation that include increased IFN-γ production and cytotoxicity against leukemic cell lines. They are called ‘memory-like’ due to their highly desirable feature of immune-memory, reflected by their persistence and pronounced anti-cancer activity observed in clinical studies for weeks to months in duration (reviewed in Berrien-Elliott et al., 2023). Through the application of ImmunityBio’s proprietary GMP-in-a-Box bioreactors and cytokines, the company has not only developed a new method that yields multiple doses from a single lymphocyte collection, but also a method to generate M-ceNK cells from cord blood (allogeneic) so that collection from the patient may not be necessary. The company has also found that the efficacy of M-ceNK cells can be further amplified by the IL-15 superagonist N-803. Because the generated M-ceNK cells are stored using our optimized cryopreservation protocol, they have maximum shelf-life and potency upon recovery, a necessity for any off-the-shelf product.
The safety and preliminary efficacy of M-ceNK cells in locally advanced or metastatic solid tumors are currently being assessed in the Phase 1 clinical trial, QUILT-3.076, which is actively enrolling patients at this time (NCT04898543).
M-ceNK cells and N-803 are investigational. Safety and efficacy of these investigational agents have not been established by any Health Authority or Agency, including the FDA.