Medicenna Presents Preclinical Data Demonstrating Potent Immune Modulating Effects of an IL-2/IL-13 Dual Specific Cytokine at the 2021 AACR Annual Meeting
-- The IL-2/IL-13 dual specific cytokine selectively stimulates anti-cancer immune cells and inhibits M2a polarization of pro-tumoral macrophages
-- Data demonstrate the potential to overcome immunotherapy resistance mechanisms and treat immunologically “cold” tumors
MDNA19-MDNA413 is composed of an IL-2 super-agonist (MDNA19) linked to an IL-13 super-antagonist (MDNA413). Data presented in the poster indicate that this DUal CytoKine (DUCK CancerTM) simultaneously activates a pro-inflammatory anti-tumor response, due to its highly selective binding and signaling via the intermediate affinity IL-2 receptor (CD122/CD132), while inhibiting pro-tumoral immune pathways by blocking IL4/IL13 signaling via the Type 2 IL-4 receptor (IL-4R/IL-13R1).
“MDNA19-MDNA413’s ability to mediate both IL-2 and IL-4/IL-13 signaling has the potential to address a significant unmet medical need for effective therapies against immunologically cold tumors,” said
Key data and conclusions from the AACR poster include:
- MDNA19-MDNA413 showed enhanced signaling in cancer killing effector T cells and NK cells and reduced activation of pro-tumor Treg cells corresponding to a 209-fold and 90-fold enhancement in CD8/Treg and NK/Treg ratios, respectively, when compared to native IL-2.
- MDNA19-MDNA413 selectively binds and inhibits both, IL-4 and IL-13 signaling, via the alpha 1 subunit (IL13Rα1) of the Type II IL-4 receptor, which is normally associated with pro-tumoral effects due to stimulation of Myeloid Derived Suppressor Cells (MDSCs) and M2a polarization of Tumor Associated Macrophages (TAMs), while showing reduced affinity for the IL13Rα2 decoy receptor.
- Compared to long-acting Fc fusion of IL-13, MDNA19-MDNA413 is ~240 times more selective for IL13Rα1 over IL13Rα2.
- MDNA19-MDNA413 potently inhibited both IL-4 and IL-13 mediated pSTAT6 activity with an IC50 of 8.0 and 12.3 nM, respectively.
- MDNA19-MDNA413 effectively inhibited IL-13-induced polarization of pro-tumor M2a macrophages
The electronic poster, titled “Modulation of Immune Responses to Cancer by Bi-specific IL-2/IL-13 Superkines” is available for on-demand viewing on the AACR Annual meeting 2021 e-poster website and can also be found on the “Events and Presentations” page of Medicenna’s website.
In addition to its BiSKITsTM program, Medicenna also continues to advance the development of MDNA11, a potentially best-in-class IL-2 Superkine. The Company expects to submit to regulatory agencies an application to commence its Phase 1/2a clinical trial in mid-2021.
Medicenna is a clinical stage immunotherapy company focused on the development of novel, highly selective versions of IL-2, IL-4 and IL-13 Superkines and first in class Empowered Superkines for the treatment of a broad range of cancers. Medicenna's long-acting IL-2 Superkine asset, MDNA11, is a next-generation IL-2 with superior CD122 binding without CD25 affinity and therefore preferentially stimulates cancer killing effector T cells and NK cells when compared to competing IL-2 programs. Medicenna's lead IL4 Empowered Superkine, MDNA55, has completed a Phase 2b clinical trial for rGBM, the most common and uniformly fatal form of brain cancer. MDNA55 has been studied in five clinical trials involving 132 subjects, including 112 adults with rGBM. MDNA55 has obtained Fast-Track and Orphan Drug status from the FDA and FDA/EMA, respectively.
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Source: Medicenna Therapeutics Corp.