Fate Therapeutics Presents Pan-tumor Targeting Preclinical Data for FT836 MICA/B-targeted CAR T-cell Product Candidate at 2024 SITC Annual Meeting
Fate Therapeutics presented preclinical data for FT836, a novel CAR T-cell product candidate targeting MICA/B proteins expressed on cancer cells, at the 2024 SITC Annual Meeting. FT836 incorporates the company's Sword & Shield technology, designed to promote functional persistence without conditioning chemotherapy. The preclinical data demonstrated robust antigen-mediated expansion and durable anti-tumor activity across various solid tumors. The product uniquely targets the α3 domain of MICA/B, stabilizing expression and inducing cytolytic killing of tumor cells. Notably, treatment with chemotherapy or radiation therapy enhanced FT836's cytolytic activity, suggesting potential combination therapy opportunities.
Fate Therapeutics ha presentato dati preclinici su FT836, un nuovo candidato prodotto CAR T-cell che mira alle proteine MICA/B espresse sulle cellule cancerose, durante il meeting annuale SITC 2024. FT836 integra la tecnologia Sword & Shield dell'azienda, progettata per promuovere la persistenza funzionale senza la chemioterapia di condizionamento. I dati preclinici hanno dimostrato un'espansione robusta mediata dall'antigene e un'attività antitumorale duratura su vari tumori solidi. Il prodotto colpisce in modo unico il dominio α3 di MICA/B, stabilizzando l'espressione e inducendo la morte delle cellule tumorali. È interessante notare che il trattamento con chemioterapia o radioterapia ha potenziato l'attività citotossica di FT836, suggerendo potenziali opportunità di terapia combinata.
Fate Therapeutics presentó datos preclínicos sobre FT836, un nuevo candidato a producto CAR T-cell que dirige proteínas MICA/B expresadas en células cancerosas, en la Reunión Anual de SITC 2024. FT836 incorpora la tecnología Sword & Shield de la compañía, diseñada para promover la persistencia funcional sin quimioterapia de acondicionamiento. Los datos preclínicos demostraron una expansión robusta mediada por antígenos y una duradera actividad antitumoral en varios tumores sólidos. El producto apunta de manera única al dominio α3 de MICA/B, estabilizando la expresión e induciendo la muerte citolítica de las células tumorales. Notablemente, el tratamiento con quimioterapia o radioterapia mejoró la actividad citolítica de FT836, sugiriendo potenciales oportunidades de terapia combinada.
Fate Therapeutics는 2024 SITC 연례 회의에서 암세포에 발현된 MICA/B 단백질을 표적으로 하는 새로운 CAR T세포 제품 후보인 FT836의 전임상 데이터를 발표했습니다. FT836은 conditioning 화학요법 없이 기능적 지속성을 촉진하도록 설계된 회사의 Sword & Shield 기술을 통합하고 있습니다. 전임상 데이터는 다양한 고형 종양에서 강력한 항원 매개 확장 및 지속적인 항종양 활성을 입증했습니다. 이 제품은 MICA/B의 α3 도메인을 독특하게 표적으로 하여 발현을 안정화하고 종양 세포의 세포 독성 사멸을 유도합니다. 특히 화학요법이나 방사선 요법을 통해 FT836의 세포 독성 활성이 향상되어 잠재적인 병용 요법 기회를 제안합니다.
Fate Therapeutics a présenté des données précliniques sur FT836, un nouveau candidat produit CAR T-cell ciblant les protéines MICA/B exprimées sur les cellules cancéreuses, lors de la réunion annuelle SITC 2024. FT836 intègre la technologie Sword & Shield de l'entreprise, conçue pour promouvoir la persistance fonctionnelle sans chimiothérapie de conditionnement. Les données précliniques ont montré une expansion robuste médiée par l'antigène et une activité anti-tumorale durable dans divers tumeurs solides. Le produit cible de manière unique le domaine α3 de MICA/B, stabilisant l'expression et induisant la mort cytolytique des cellules tumorales. Notamment, le traitement par chimiothérapie ou radiothérapie a amélioré l'activité cytolytique de FT836, suggérant des opportunités potentielles de thérapie combinée.
Fate Therapeutics hat auf dem 2024 SITC-Jahrestreffen präklinische Daten zu FT836 präsentiert, einem neuartigen CAR T-Zell-Produktkandidaten, der auf die in Krebszellen exprimierten MICA/B-Proteine abzielt. FT836 integriert die Sword & Shield-Technologie des Unternehmens, die darauf abzielt, eine funktionale Persistenz ohne konditionierende Chemotherapie zu fördern. Die präklinischen Daten zeigten eine robuste antigenvermittelte Expansion und eine dauerhafte anti-tumorale Aktivität über verschiedene solide Tumoren hinweg. Das Produkt zielt einzigartig auf die α3-Domäne von MICA/B ab, stabilisiert die Expression und induziert die zytolytische Abtötung von Tumorzellen. Bemerkenswert ist, dass die Behandlung mit Chemotherapie oder Strahlentherapie die zytolytische Aktivität von FT836 verstärkte, was auf potenzielle Möglichkeiten für eine Kombinationstherapie hinweist.
- Demonstrated robust anti-tumor activity across multiple solid tumor types
- Product shows potential effectiveness without conditioning chemotherapy
- Enhanced cytolytic activity when combined with standard cancer treatments
- Novel targeting mechanism addresses common cancer resistance mechanisms
- Still in preclinical stage, requiring extensive clinical trials before commercialization
- No human efficacy data available yet
Insights
The preclinical data for FT836 represents a significant advancement in CAR T-cell therapy development. The novel MICA/B targeting mechanism addresses a critical gap in solid tumor treatment by targeting proteins expressed during cellular stress and malignant transformation. The unique α3 domain targeting approach helps overcome the common tumor escape mechanism of MICA/B shedding.
The innovative Sword & Shield technology could be a game-changer by potentially eliminating the need for conditioning chemotherapy, which is currently a significant burden in CAR T-cell therapy. The demonstrated persistence and anti-tumor activity in the presence of alloreactive T cells suggests improved safety and efficacy profiles.
The pan-tumor potential and synergy with standard chemotherapy and radiation therapy indicate broad therapeutic applications. However, as these are preclinical results, significant clinical validation will be required to prove real-world efficacy.
The multiplexed engineering approach in FT836 represents sophisticated genetic modification technology. The complete knockout of CD58 combined with the 4-1BB-targeted CAR demonstrates advanced gene editing capabilities. This dual-action mechanism, targeting while evading host immune responses, showcases innovative synthetic biology design.
The iPSC-derived platform offers significant manufacturing advantages over traditional autologous CAR T-cell production, potentially enabling more cost-effective and standardized production of off-the-shelf cell therapies. The technology's ability to function without conditioning chemotherapy could significantly improve the therapeutic window and reduce treatment-related complications.
Multiplexed-engineered, iPSC-derived CAR T Cell Targets Proteins Expressed on Cancer Cells in Response to Cellular Stress and Malignant Transformation
Off-the-shelf Product Candidate Incorporates Novel Sword & Shield Technology Designed to Promote Functional Persistence without Conditioning Chemotherapy
FT836 Preclinical Data Shows Robust Antigen-mediated Expansion, Functional Persistence, and Durable Anti-tumor Activity in the Presence of Alloreactive T Cells
SAN DIEGO, Nov. 08, 2024 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune disorders, today presented initial preclinical data for FT836, a multiplexed-engineered, chimeric antigen receptor (CAR) T-cell product candidate targeting major histocompatibility complex (MHC) proteins A (MICA) and B (MICB) at the 2024 Society of Immunotherapy of Cancer (SITC) 39th Annual Meeting being held in Houston, TX on November 6-10, 2024. The expression of MICA/B cell-surface proteins is induced by cellular stress or malignant transformation, and is detectable across many types of cancer cells with limited expression on healthy tissue. FT836 incorporates multiple next-generation synthetic controls of CAR T-cell function including the Company’s novel Sword & Shield technology, which is comprised of a constellation of genetic edits that both target and evade host alloreactive immune cells and is designed to promote functional persistence of off-the-shelf CAR T-cell therapies without conditioning chemotherapy.
“The novel suite of synthetic controls incorporated into FT836 is intended to address critical challenges that have limited CAR T-cell safety and efficacy in treating solid tumors including on-target, off-tumor toxicity, effector cell suppression in the tumor microenvironment, tumor heterogeneity, and limited functional persistence,” said Bob Valamehr, Ph.D., President of Research & Development of Fate Therapeutics. “Our FT836 preclinical data presented today at SITC support the pan-cancer activity of MICA/B targeting, and indicate that our next-generation, iPSC-derived CAR T-cell platform has the potential to drive potent and durable anti-tumor activity without the need for administration of conditioning chemotherapy to deplete host immune cells.”
Preclinical Data
MICA/B targeting is emerging as a novel cancer-specific strategy to attack a wide range of solid tumors, however, proteolytic cleavage and shedding of MICA/B at the membrane-proximal α3 domain is a common mechanism of cancer resistance and escape from canonical NKG2D-mediated recognition. FT836 is designed to uniquely target and bind the α3 domain, which has been shown to stabilize MICA/B expression and induce robust cytolytic killing of tumor cells. At an oral presentation today at SITC entitled “Development of an Off-the-Shelf, MICA/B Targeting CAR T Cell to Overcome Pan-tumor Escape Mechanism for Solid Tumors”, scientists from the Company highlighted that FT836 exerted potent and durable anti-tumor activity in vivo across a broad array of solid tumors. In addition, treatment of tumor cells with chemotherapy or radiation therapy in vitro elicited an increase in MICA/B expression and further enhanced the cytolytic activity of FT836, indicating the potential for combination with standard-of-care regimens used for the treatment of solid tumors.
Novel Sword & Shield Technology
FT836 is also the Company’s first product candidate to incorporate its novel Sword & Shield technology, which utilizes a 4-1BB-targeted CAR (ADR) alongside the complete knock-out of CD58 (CD58KO), to both target and evade host alloreactive immune cells. In preclinical studies presented at SITC, iPSC-derived Sword & Shield CAR T cells demonstrated functional persistence and durable anti-tumor activity in vivo that was uniquely maintained upon supraphysiological challenge with alloreactive T cells, indicating the potential of Sword & Shield CAR T cells to thrive without administration of conditioning chemotherapy to deplete host immune cells. The Company’s novel Sword & Shield technology was also featured in a poster presentation at SITC entitled “Alloimmune Defense Receptor Combined with Genetic Ablation of Adhesion Ligand CD58 is a Comprehensive Approach to Promote Functional Persistence of Allogeneic Cell Therapies without Conditioning Chemotherapy”.
About Fate Therapeutics’ iPSC Product Platform
Human induced pluripotent stem cells (iPSCs) possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s proprietary iPSC product platform combines multiplexed-engineering of human iPSCs with single-cell selection to create clonal master iPSC lines. Analogous to master cell lines used to mass produce biopharmaceutical drug products such as monoclonal antibodies, the Company utilizes its clonal master iPSC lines as a starting cell source to manufacture engineered cell products which are well-defined and uniform in composition, can be stored in inventory for off-the-shelf availability, can be combined and administered with other therapies, and can potentially reach a broad patient population. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the manufacture of cell therapies using patient- or donor-sourced cells. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 500 issued patents and 500 pending patent applications.
About Fate Therapeutics, Inc.
Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune diseases. Using its proprietary iPSC product platform, the Company has established a leadership position in creating multiplexed-engineered master iPSC lines and in the manufacture and clinical development of off-the-shelf, iPSC-derived cell products. The Company’s pipeline includes iPSC-derived natural killer (NK) cell and T-cell product candidates, which are selectively designed, incorporate novel synthetic controls of cell function, and are intended to deliver multiple therapeutic mechanisms to patients. Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit www.fatetherapeutics.com.
Forward-Looking Statements
This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the Company's product candidates, clinical studies and preclinical research and development programs, its ongoing and planned clinical studies, the safety and therapeutic potential of the Company’s product candidates, and the Company’s clinical and product development strategy. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that the Company’s research and development programs and product candidates, including those product candidates in clinical investigation, may not demonstrate the requisite safety, efficacy, or other attributes to warrant further development or to achieve regulatory approval, the risk that results observed in prior studies of the Company’s product candidates, including preclinical studies and clinical trials, will not be observed in ongoing or future studies involving these product candidates, the risk of a delay or difficulties in the manufacturing of the Company’s product candidates or in the initiation and conduct of, or enrollment of patients in, any clinical trials, the risk that the Company may cease or delay preclinical or clinical development of any of its product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials, changes in the therapeutic, regulatory, or competitive landscape for which the Company’s product candidates are being developed, the amount and type of data to be generated or otherwise to support regulatory approval, difficulties or delays in patient enrollment and continuation in the Company’s ongoing and planned clinical trials, difficulties in manufacturing or supplying the Company’s product candidates for clinical testing, failure to demonstrate that a product candidate has the requisite safety, efficacy, or other attributes to warrant further development, and any adverse events or other negative results that may be observed during preclinical or clinical development), and the risk that its product candidates may not produce therapeutic benefits or may cause other unanticipated adverse effects. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Company’s actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Company’s periodic filings with the Securities and Exchange Commission, including but not limited to the Company’s most recently filed periodic report, and from time to time in the Company’s press releases and other investor communications. Fate Therapeutics is providing the information in this release as of this date and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise.
Contact:
Christina Tartaglia
Precision AQ
212.362.1200
christina.tartaglia@precisionaq.com
FAQ
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