BOSTON, April 04, 2024 (GLOBE NEWSWIRE) -- Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), a clinical stage immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer patients, today announced the publication of a peer-reviewed research paper in Nature Communications. The research was conducted by scientists at Sensei Biotherapeutics in collaboration with genOway and the laboratory of Dr. Robert Schreiber at the Washington University, St. Louis School of Medicine.
The paper describes Sensei Biotherapeutics' approach to the discovery and development of SNS-101, which was designed to potently and selectively target the active protonated form of VISTA, a protein that plays a significant role in suppressing T-cell activation. VISTA was previously considered undruggable due to its extensive expression on myeloid cells, leading to safety issues such as cytokine release syndrome (CRS), in addition to a pharmacokinetic sink, which poses a significant challenge in reaching therapeutically relevant concentrations. The paper details the mechanism and characteristics of SNS-101, a novel pH-sensitive monoclonal antibody. SNS-101 was shown to bind to a novel epitope of VISTA that is remodeled under low pH conditions, switching VISTA into an active state that engenders extensive T-cell suppression. SNS-101 is designed to block VISTA by inhibiting its interaction with PSGL-1 on T-cells resulting in T-cell activation. Subsequently, in various preclinical models, SNS-101 was shown to mitigate CRS risk and maintain a favorable pharmacokinetic and safety profile, all of which had thwarted the clinical development of first generation, non-pH sensitive anti-VISTA antibodies.
"The publication of this research in Nature Communications serves as important validation for our tumor-targeting approach and confirms our ability to design highly selective antibodies that target VISTA under the unique conditions of the tumor microenvironment," said Edward van der Horst, Ph.D., Chief Scientific Officer of Sensei Bio. "Our studies of SNS-101 highlight the therapeutic potential for a VISTA-directed immunotherapy unhindered by dose limiting toxicities and off-target effects. We believe the initial clinical data we presented from our Phase 1/2 clinical study further support these important preclinical findings. We are excited to see the impact SNS-101 can have in patients as we advance our ongoing clinical study."
波士頓,2024年4月4日(GLOBE NEWSWIRE)——專注於發現和開發下一代癌症患者療法的臨床階段免疫腫瘤學公司Sensei Biotherapeutics, Inc.(納斯達克股票代碼:SNSE)今天宣佈在《自然通訊》上發表了一篇經過同行評審的研究論文。這項研究由Sensei Biotherapeutics的科學家與GenoWay和華盛頓大學聖路易斯醫學院羅伯特·施雷伯博士的實驗室合作進行。
該論文描述了Sensei Biotherapeutics發現和開發 SNS-101 的方法,該方法旨在有效、有選擇地靶向活性質子化形式的VISTA,VISTA是一種在抑制T細胞激活中起着重要作用的蛋白質。由於VISTA在骨髓細胞上廣泛表達,此前被認爲是不可藥物的,這會導致諸如細胞因子釋放綜合徵(CRS)之類的安全問題,此外還存在藥代動力學匯,這在達到與治療相關的濃度方面構成了重大挑戰。本文詳細介紹了一種新型的 pH 敏感單克隆抗體 SNS-101 的機理和特性。事實證明,SNS-101 可與在低 pH 值條件下重塑的 VISTA 的新表位結合,使 VISTA 進入活性狀態,從而對 T 細胞產生廣泛抑制。SNS-101 旨在通過抑制 VISTA 與 PSGL-1 在 T 細胞上的相互作用來阻斷 VISTA,進而激活 T 細胞。隨後,在各種臨床前模型中,SNS-101 被證明可以降低 CRS 風險並保持良好的藥代動力學和安全性,所有這些都阻礙了第一代非 pH 敏感抗 VISTA 抗體的臨床開發。
Sensei Bio首席科學官愛德華·範德霍斯特博士說:“在《自然通訊》上發表這項研究是對我們腫瘤靶向方法的重要驗證,也證實了我們在腫瘤微環境的獨特條件下設計靶向VISTA的高選擇性抗體的能力。”“我們對 SNS-101 的研究突顯了Vista定向免疫療法的治療潛力,不受劑量限制毒性和脫靶效應的阻礙。我們認爲,我們在1/2期臨床研究中提供的初步臨床數據進一步支持了這些重要的臨床前發現。隨着我們正在進行的臨床研究的推進,我們很高興看到 SNS-101 可能對患者產生的影響。”