Medicenna Presents Updated Preclinical Data on MDNA113, a First-in-Class, Targeted and Masked Bi-functional Anti-PD1-IL2 Superkine, at the 2024 Annual Meeting of the American Association for Cancer Research (AACR)
Medicenna Presents Updated Preclinical Data on MDNA113, a First-in-Class, Targeted and Masked Bi-functional Anti-PD1-IL2 Superkine, at the 2024 Annual Meeting of the American Association for Cancer Research (AACR)
MDNA113 is targeted to the tumor site where it is activated to simultaneously deliver two immunotherapies, an IL-2 superkine and anti-PD1 antibody, to the same cancer fighting immune cells in the tumor micro-environment (TME) to maximize efficacy and minimize systemic toxicity
MDNA113 靶向腫瘤部位，激活該部位，可同時向腫瘤微環境 (TME) 中的同一個抗癌免疫細胞提供兩種免疫療法，即 IL-2 超因子和抗 PD1 抗體，以最大限度地提高療效並最大限度地減少全身毒性
MDNA113 is our most advanced pre-clinical candidate that targets IL-13Rα2, a tumor associated antigen, which is overexpressed by immunologically "cold" tumors with high unmet needs in pancreatic, prostate, ovarian, breast and brain cancer affecting over two million patients every year
MDNA113 是我們最先進的臨床前候選藥物，它靶向腫瘤相關抗原IL-13Rα2，這種抗原被免疫學 “冷” 腫瘤過度表達，胰腺癌、前列腺癌、卵巢癌、乳腺癌和腦癌的需求未得到滿足，每年影響超過200萬名患者
TORONTO and HOUSTON, April 09, 2024 (GLOBE NEWSWIRE) -- Medicenna Therapeutics Corp. ("Medicenna" or the "Company") (TSX: MDNA), a clinical-stage immunotherapy company focused on the development of Superkines, today announced new preclinical data on MDNA113, the Company's novel T-MASK (Targeted Metallo/protease Activated SuperKine) candidate, an IL-13R⍺2 (Interleukin-13 receptor alpha2) specific superkine featuring unique masking and tumor targeting characteristics, were presented at the 2024 Annual Meeting of the American Association for Cancer Research (AACR) held in San Diego, CA, on April 9th, 2024.
多倫多和休斯頓，2024年4月9日（GLOBE NEWSWIRE）——專注於開發Superkines的臨床階段免疫療法公司Medicenna Therapeutics Corp.（“MDINA” 或 “公司”）（多倫多證券交易所股票代碼：MDNA）今天公佈了該公司的新型T-MASK（靶向金屬/蛋白酶活化SuperKine）候選藥物 IL-13R2（在美國癌症研究協會（AACR）2024年年會上發佈了具有獨特掩蓋和腫瘤靶向特性的白介素-13受體（α2）特異性超因子 MDNA113於 2024 年 4 月 9 日在加利福尼亞州聖地亞哥舉行。
"We are pleased to show preclinical data demonstrating the ability of Medicenna's first T-MASK candidate, MDNA113 to enhance tumor accumulation and tolerability of our potent bi-functional immune modulator, anti-PD1-IL-2SK," said Fahar Merchant, Ph.D., President and Chief Executive Officer of Medicenna. "MDNA113 has novel features, including the tunable blockade of the IL-2R agonism to reduce peripheral immune stimulation for enhanced tolerability, and tumor targeting to IL-13R⍺2 which is linked to aggressive cancers that annually affect over 2 million patients world-wide. The cleavage and release of the IL-13 tumor-targeting/masking domain by matrix metalloproteases restores IL-2R signaling within the tumor microenvironment, thereby benefiting from the simultaneous and synergistic activity of IL-2R agonism and immune checkpoint blockade at the tumor site."
Medicenna總裁兼首席執行官法哈爾·默特博士表示：“我們很高興展示臨床前數據，表明Medicenna的首款T-MASK候選藥物 MDNA113 能夠增強我們的強效雙功能免疫調節劑抗PD1-IL-2SK的腫瘤積累和耐受性。”“MDNA113 具有新特徵，包括可調阻斷 IL-2R 激動作用以減少外周免疫刺激以增強耐受性，以及靶向 IL-13R2 的腫瘤，後者與侵襲性癌症有關，侵襲性癌症每年影響全球超過 200 萬名患者。基質金屬蛋白酶分裂和釋放 IL-13 腫瘤靶向/掩蓋結構域可恢復 IL-2R 在腫瘤微環境中的信號，從而受益於腫瘤部位的 IL-2R 激動作用和免疫檢查點阻斷的同步協同活性。”
The Company selected MDNA113, a novel, first-in-class tumor-targeted and tumor-activated bi-functional anti-PD1-IL-2 superkine with high selectivity and affinity for IL-13Rα2, a tumor associated antigen expressed in many aggressive solid tumors. The IL-13 Superkine (MDNA213) is a highly specific tumor-targeting/masking domain which is fused via a protease sensitive linker to a bi-functional immunotherapy domain (MDNA223) containing an IL-2 Superkine fused to an anti-PD1 antibody.
該公司選擇了 MDNA113，這是一種新型、同類首創的腫瘤靶向和腫瘤激活的雙功能抗PD1-IL-2超因子，對IL-13Rα2具有高選擇性和親和力，IL-13Rα2是一種在許多侵襲性實體瘤中表達的腫瘤相關抗原。IL-13 Superkine（MDNA213）是一種高度特異的腫瘤靶向/屏蔽結構域，它通過蛋白酶敏感的連接劑融合到包含與抗PD1抗體融合的IL-2超級因子的雙功能免疫治療結構域（MDNA223）。
Key findings presented at the conference include:
會議上提出的主要發現包括：
When not activated, MDNA113 shows reduced IL-2R agonism with no change to PD-1/PDL-1 blockade activity.
Cleavage and activation of MDNA113 by cancer specific enzymes (metalloproteases) releases the T-MASK domain (MDNA213), restoring activity of the IL-2 Superkine at the tumor site.
MDNA113 shows attenuated systemic lymphocyte expansion compared to non-masked version (MDNA223), consistent with design of MDNA113.
MDNA113 is better tolerated than non-masked counterpart (MDNA223), supporting higher and more efficacious dosing schedule.
MDNA113 selectively binds IL-13R⍺2 positive tumor cells in vitro, and durably accumulates (>7 days) in IL-13R⍺2 positive tumors in mice.
Cleavable MDNA113 shows similar efficacy as non-masked MDNA223 in mouse tumor models by either localized (intra-tumoral) or systemic (intra-peritoneal) delivery, consistent with proteolytic activation within TME.
Single neoadjuvant treatment with MDNA113 in a highly invasive orthotopic 4T1.2 breast cancer model significantly increases survival by preventing metastasis.
In summary, the T-MASK platform exemplified by MDNA113, facilitates tumor targeting and minimizes systemic toxicity while maximizing therapeutic activity at the tumor site.
未激活時，MDNA113 顯示出 IL-2R 激動作用降低，PD-1/PDL-1 的阻斷活性沒有變化。
通過癌症特異性酶（金屬蛋白酶）分解和激活 MDNA113 會釋放 T-MASK 結構域（MDNA213），恢復 IL-2 超因子在腫瘤部位的活性。
與非掩膜版本（MDNA223）相比，MDNA113 的全身淋巴細胞擴張減弱，與 MDNA113 的設計一致。
MDNA113 的耐受性優於非掩膜對應物 (MDNA223)，支持更高、更有效的給藥時間表。
MDNA113 在體外選擇性結合 IL-13R2 陽性腫瘤細胞，並在小鼠體內 IL-13R2 陽性腫瘤中持久積累（>7 天）。
Cleavable MDNA113 通過局部（腫瘤內）或全身（腹膜內）遞送，在小鼠腫瘤模型中表現出與非掩膜 MDNA223 相似的療效，這與 TME 內的蛋白水解激活一致。
在高侵入性原位 4T1.2 乳腺癌模型中使用 MDNA113 進行單一新輔助治療可防止轉移，從而顯著提高存活率。
總而言之，以 MDNA113 爲例的 T-MASK 平台可促進腫瘤靶向並最大限度地減少全身毒性，同時最大限度地提高腫瘤部位的治療活性。
The poster, "Characterization of MDNA113, a Tumor-Targeting Anti-PD1-IL-2SK Immunocytokine with Conditional Activation to Increase Tolerability and Maximize Efficacy" can be found on the AACR website for conference registrants. It will be also available on the Scientific Presentations page of Medicenna's website following the conclusion of the 2024 Annual Meeting of AACR.
海報 “MDNA113 的表徵，一種靶向腫瘤的抗 PD1-IL-2SK 免疫細胞因子，具有條件激活，可提高耐受性並最大限度地提高療效”，可在AACR網站上爲會議註冊者找到。2024年AACR年會結束後，它還將在Medicenna網站的科學演示頁面上公佈。
About the T-MASK Platform
關於 T-MASK 平台
Medicenna's novel T-MASK (Targeted Metallo/protease Activated SuperKine) platform involves fusion of a dual tumor-targeting/masking domain to an immune modulator (such as a Superkine or a BiSKIT) via a matrix metalloprotease (MMP) sensitive linker to (i) reduce and fine-tune the potency of the immune modulator, (ii) increase its systemic tolerability (iii) prolong its retention in the TME and (iv) to maximize and restore full potency at the intended target site. The T-MASK platform offers opportunity to target and fine-tune immune cell stimulation in the TME to improve the therapeutic index of Medicenna's Superkine and BiSKIT platforms.
Medicenna 的新型 T-MASK（靶向金屬/蛋白酶活化 SuperKine）平台涉及通過基質金屬蛋白酶（MMP）敏感連接劑將雙腫瘤靶向/屏蔽結構域與免疫調節劑（例如 Superkine 或 BisKit）融合，以（i）降低和微調免疫調節劑的效力，（iii）提高其全身耐受性（iii）延長其全身耐受性（iii）延長其耐受性保留在 TME 中，以及（iv）最大限度地發揮和恢復預期目標部位的全部效力。T-MASK平台爲靶向和微調TME中的免疫細胞刺激提供了機會，以提高Medicenna的Superkine和BisKit平台的治療指數。
About MDNA113
關於 MDNA113
MDNA113 is a novel, first-in-class tumor-targeted and tumor-activated bi-functional anti-PD1-IL-2 Superkine with high affinity for IL-13Rα2 without binding to the functional IL-13R⍺1. IL-13Rα2 is overexpressed in a wide range of solid tumors, including cold tumors. IL-13Rα2 is a tumor-associated antigen with minimal to no expression in normal tissues but is highly expressed by a wide range of tumors including "cold" tumors. IL-13Rα2 expressing tumors also have abundant MMPs in the TME that may efficiently activate MDNA113. IL-13Rα2 expression is associated with poor clinical outcome in multiple tumor types with an annual world-wide incidence of over 2 million in different tumor types including prostate cancer, pancreatic cancer, ovarian cancer, liver cancer, breast cancer and brain cancer, and among others.
MDNA113 是一種新型、同類首創的腫瘤靶向和腫瘤激活的雙功能抗PD1-IL-2 Superkine，對白細胞介素13Rα2具有很高的親和力，不會與功能性IL-13R1結合。IL-13Rα2在各種實體瘤中過度表達，包括感冒性腫瘤。IL-13Rα2 是一種腫瘤相關抗原，在正常組織中幾乎沒有表達，但它在包括 “冷” 腫瘤在內的各種腫瘤中高度表達。表達 IL-13Rα2 的腫瘤在 TME 中也含有豐富的 MMP，可以有效激活 MDNA113。IL-13Rα2的表達與多種腫瘤類型的臨床效果不佳有關，全球每年在不同類型的腫瘤中發病率超過200萬例，包括前列腺癌、胰腺癌、卵巢癌、肝癌、乳腺癌和腦癌等。
譯文內容由第三人軟體翻譯。