Cellectis Presents ‘Smart CAR T’ Strategy to Enhance Efficacy Against Solid Tumors at AACR-IO 2025
Cellectis (NASDAQ: CLLS) presented its 'Smart CAR T' strategy at AACR-IO 2025, showcasing an innovative approach to enhance CAR T cell efficacy against solid tumors. The presentation focused on a technique using interleukin 2 (IL-2) to improve treatment outcomes.
The company's research demonstrates that their TALEN® gene editing technology enables CAR T cells to express a CAR-inducible IL-2 variant (IL-2v) immunocytokine, which is activated by tumor-specific signals within the solid tumor microenvironment (TME). This engineered IL-2v boosts anti-tumor activity both in vitro and in vivo, while minimizing systemic toxicity by anchoring to the FAP protein present in the TME.
The development aims to improve CAR T-cell expansion and persistence without the toxicity risks typically associated with high-dose IL-2 administration, potentially representing a safer and more effective treatment approach for solid tumors.
Cellectis (NASDAQ: CLLS) ha presentato la sua strategia 'Smart CAR T' all'AACR-IO 2025, mostrando un approccio innovativo per migliorare l'efficacia delle cellule CAR T contro i tumori solidi. La presentazione si è concentrata su una tecnica che utilizza interleuchina 2 (IL-2) per migliorare i risultati del trattamento.
La ricerca dell'azienda dimostra che la loro tecnologia di editing genetico TALEN® consente alle cellule CAR T di esprimere una variante di IL-2 indotta da CAR (IL-2v) come immunocitochina, attivata da segnali specifici del tumore all'interno del microambiente tumorale solido (TME). Questa IL-2v ingegnerizzata potenzia l'attività anti-tumorale sia in vitro che in vivo, riducendo al contempo la tossicità sistemica ancorandosi alla proteina FAP presente nel TME.
Lo sviluppo mira a migliorare l'espansione e la persistenza delle cellule CAR T senza i rischi di tossicità generalmente associati alla somministrazione di IL-2 ad alte dosi, rappresentando potenzialmente un approccio terapeutico più sicuro ed efficace per i tumori solidi.
Cellectis (NASDAQ: CLLS) presentó su estrategia 'Smart CAR T' en AACR-IO 2025, mostrando un enfoque innovador para mejorar la eficacia de las células CAR T contra tumores sólidos. La presentación se centró en una técnica que utiliza interleucina 2 (IL-2) para mejorar los resultados del tratamiento.
La investigación de la empresa demuestra que su tecnología de edición genética TALEN® permite que las células CAR T expresen una variante de IL-2 inducible por CAR (IL-2v) como inmunocitoquina, que se activa mediante señales específicas del tumor dentro del microambiente tumoral sólido (TME). Esta IL-2v diseñada aumenta la actividad antitumoral tanto in vitro como in vivo, al tiempo que minimiza la toxicidad sistémica al anclarse a la proteína FAP presente en el TME.
El desarrollo tiene como objetivo mejorar la expansión y persistencia de las células CAR T sin los riesgos de toxicidad típicamente asociados con la administración de IL-2 a altas dosis, representando potencialmente un enfoque terapéutico más seguro y efectivo para los tumores sólidos.
Cellectis (NASDAQ: CLLS)는 AACR-IO 2025에서 '스마트 CAR T' 전략을 발표하며 고형 종양에 대한 CAR T 세포의 효능을 향상시키기 위한 혁신적인 접근 방식을 선보였습니다. 발표는 인터루킨 2 (IL-2)를 사용하여 치료 결과를 개선하는 기술에 초점을 맞추었습니다.
회사의 연구는 그들의 TALEN® 유전자 편집 기술이 CAR T 세포가 종양 특이적 신호에 의해 활성화되는 CAR 유도 IL-2 변형체 (IL-2v) 면역 사이토카인을 발현하도록 한다는 것을 보여줍니다. 이 엔지니어링된 IL-2v는 고형 종양 미세환경 (TME) 내에서 항종양 활성을 증가시키면서 FAP 단백질에 고정되어 전신 독성을 최소화합니다.
이 개발은 일반적으로 고용량 IL-2 투여와 관련된 독성 위험 없이 CAR T 세포의 확장 및 지속성을 개선하는 것을 목표로 하며, 고형 종양에 대한 보다 안전하고 효과적인 치료 접근 방식을 나타낼 수 있습니다.
Cellectis (NASDAQ: CLLS) a présenté sa stratégie 'Smart CAR T' lors de l'AACR-IO 2025, mettant en avant une approche innovante pour améliorer l'efficacité des cellules CAR T contre les tumeurs solides. La présentation s'est concentrée sur une technique utilisant interleukine 2 (IL-2) pour améliorer les résultats du traitement.
Les recherches de l'entreprise montrent que leur technologie d'édition génique TALEN® permet aux cellules CAR T d'exprimer une variante d'IL-2 induite par CAR (IL-2v) comme immunocytokine, activée par des signaux spécifiques aux tumeurs dans le microenvironnement tumoral solide (TME). Cette IL-2v conçue augmente l'activité antitumorale à la fois in vitro et in vivo, tout en minimisant la toxicité systémique en se fixant à la protéine FAP présente dans le TME.
Le développement vise à améliorer l'expansion et la persistance des cellules CAR T sans les risques de toxicité généralement associés à l'administration d'IL-2 à fortes doses, représentant potentiellement une approche thérapeutique plus sûre et plus efficace pour les tumeurs solides.
Cellectis (NASDAQ: CLLS) stellte seine 'Smart CAR T'-Strategie auf der AACR-IO 2025 vor und präsentierte einen innovativen Ansatz zur Verbesserung der Wirksamkeit von CAR T-Zellen gegen solide Tumoren. Der Vortrag konzentrierte sich auf eine Technik, die Interleukin 2 (IL-2) verwendet, um die Behandlungsergebnisse zu verbessern.
Die Forschung des Unternehmens zeigt, dass ihre TALEN®-Gentechnologie es CAR T-Zellen ermöglicht, eine CAR-induzierbare IL-2-Variante (IL-2v) als Immunocytokin zu exprimieren, die durch tumorspezifische Signale im soliden Tumormikroenvironment (TME) aktiviert wird. Dieses konstruierte IL-2v steigert die antitumorale Aktivität sowohl in vitro als auch in vivo und minimiert gleichzeitig die systemische Toxizität, indem es an das im TME vorhandene FAP-Protein bindet.
Die Entwicklung zielt darauf ab, die Expansion und Persistenz von CAR T-Zellen ohne die typischerweise mit der Hochdosis-IL-2-Verabreichung verbundenen Toxizitätsrisiken zu verbessern, was potenziell einen sichereren und effektiveren Behandlungsansatz für solide Tumoren darstellt.
- Development of innovative 'Smart CAR T' technology showing enhanced anti-tumor activity
- Successfully demonstrated reduced toxicity compared to traditional IL-2 treatments
- Potential breakthrough in treating solid tumors with CAR T-cell therapy
- Technology still in preclinical stage, requiring further validation
- No clinical efficacy data presented yet
Insights
The presentation of Cellectis' 'Smart CAR T' technology represents a potentially significant advancement in the $5.4 billion CAR T-cell therapy market. This innovation tackles two fundamental challenges that have historically CAR T-cell therapy in solid tumors: insufficient persistence of the engineered cells and the toxicity associated with IL-2 administration.
The technology's key innovation lies in its ability to confine IL-2 activity to the tumor microenvironment through FAP protein targeting. This approach could provide Cellectis with a significant competitive advantage in the solid tumor space, where current CAR T-cell therapies have shown success. The market opportunity is substantial, as solid tumors represent approximately 90% of adult cancers.
From a technical perspective, this platform technology could be applicable across multiple solid tumor types, potentially creating a pipeline of products rather than a single therapeutic. The use of TALEN gene editing technology also provides precise control over genetic modifications, which could translate to better safety profiles in clinical applications.
However, investors should note that this is still in the preclinical stage. While the data presented shows promise, the path to commercialization will require extensive clinical trials to validate both efficacy and the proposed safety advantages. The technology's success in controlling IL-2 toxicity while maintaining therapeutic benefits will be important for clinical translation.
The strategic value of this development extends beyond immediate applications. It demonstrates Cellectis' ability to innovate in the highly competitive cell therapy space and could make the company an attractive partner for larger pharmaceutical companies seeking to expand their cell therapy portfolios.
NEW YORK, Feb. 24, 2025 (GLOBE NEWSWIRE) -- Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, showcases an innovative strategy for T cell engineering that leverages the pro-inflammatory properties of interleukin 2 (IL-2) with the objective to enhance CAR T cell efficacy against solid tumors, at the American Association for Cancer Research – Immuno-oncology (AACR-IO), taking place on February 23-26, 2025 in Los Angeles, CA.
The data are presented in a poster:
CAR induced expression of synthetically engineered FAP-IL2v immunocytokine boosts persistent anti-tumor activity of TALEN-edited allogeneic CAR T-cells without associated IL-2 toxicity
Presenter: Shipra Das, Ph.D., Associate Director Immuno-Oncology, at Cellectis.
Date/Time: February 25, 2025, 1:45-4:45 p.m. PT
Session: Poster Session B
- CAR T-cell therapies have transformed the treatment landscape for specific hematological malignancies and have shown promising preliminary efficacy in solid tumors.
- Recent studies suggest a link between the in vivo expansion and persistence of CAR-T cells and enhanced therapeutic outcomes in patients. The co-administration of interleukin-2 (IL-2) has been demonstrated to improve CAR T-cell engraftment, expansion, and functionality in preclinical models but poses toxicity risks at high doses.
- Using Cellectis’ TALEN® gene editing technology, we developed ‘Smart CAR T cells’ with the ability to express a CAR-inducible IL-2 variant (IL-2v) immunocytokine, potentiated by tumor-specific cues for localized activity within the solid tumor microenvironment (TME).
- CAR-inducible expression of this recombinant FAPscFv-IL2v boosts anti-tumor activity of engineered CAR T-cells both in vitro and in vivo. Notably, the enhancement of CAR T-cell activity mediated by IL-2v relies on its anchoring to the FAP protein, which is uniquely present in the TME, thus minimizing the systemic toxicity typically associated with circulating free IL-2 cytokines.
- This proposed cellular engineering strategy would represent an effective and safe method to substantially improve CAR T cell expansion and anti-tumor activity, while confining IL-2 activity to the tumor microenvironment.
The poster is published on Cellectis’ website.
About Cellectis
Cellectis is a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies. The company utilizes an allogeneic approach for CAR T immunotherapies in oncology, pioneering the concept of off-the-shelf and ready-to-use gene-edited CAR T-cells to treat cancer patients, and a platform to develop gene therapies in other therapeutic indications. With its in-house manufacturing capabilities, Cellectis is one of the few end-to-end gene editing companies that controls the cell and gene therapy value chain from start to finish.
Cellectis’ headquarters are in Paris, France, with locations in New York and Raleigh, NC. Cellectis is listed on the Nasdaq Global Market (ticker: CLLS) and on Euronext Growth (ticker: ALCLS). To find out more, visit www.cellectis.com and follow Cellectis on LinkedIn and X.
TALEN® is a registered trademark owned by Cellectis.
Cautionary Statement
This press release contains “forward-looking” statements within the meaning of applicable securities laws, including the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by words such as “with the objective to,” and “would,” or the negative of these and similar expressions. These forward-looking statements are based on our management’s current expectations and assumptions and on information currently available to management. Forward-looking statements include statements about the potential of the Company’s research and development programs. These forward-looking statements are made in light of information currently available to us and are subject to numerous risks and uncertainties, including with respect to the numerous risks associated with market conditions, and our ability to satisfy the conditions precedent under the Finance Contract. Furthermore, many other important factors, including those described in our Annual Report on Form 20-F as amended and in our annual financial report (including the management report) for the year ended December 31, 2023 and subsequent filings Cellectis makes with the Securities Exchange Commission from time to time, which are available on the SEC’s website at www.sec.gov, as well as other known and unknown risks and uncertainties may adversely affect such forward-looking statements and cause our actual results, performance or achievements to be materially different from those expressed or implied by the forward-looking statements. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future.
For further information on Cellectis, please contact:
Media contacts:
Pascalyne Wilson, Director, Communications, + 33 (0)7 76 99 14 33, media@cellectis.com
Patricia Sosa Navarro, Chief of Staff to the CEO, +33 (0)7 76 77 46 93
Investor Relations contact:
Arthur Stril, Chief Financial Officer & Chief Business Officer, investors@cellectis.com
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FAQ
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