Cellectis Publishes a Molecular Therapy Article on a SMART DUAL CAR T-cell Approach for Treating Recalcitrant Solid Tumors
Cellectis (NASDAQ: CLLS) has published an article in Molecular Therapy showcasing their innovative SMART DUAL CAR T-cell approach for treating solid tumors. Using TALEN® gene editing technology, Cellectis has developed allogeneic CAR T-cells that express:
1. A constitutive CAR targeting FAP+ cancer-associated fibroblasts (CAFs) in solid tumors
2. An inducible CAR, expressed only in the presence of FAP+ CAFs, targeting mesothelin
This strategy aims to overcome challenges in solid tumor treatment, including low T-cell infiltration, immunosuppressive microenvironment, and on-target off-tumor toxicity. In mice models, these SMART Dual CAR T-cells efficiently infiltrated and targeted triple-negative breast tumors without observable off-tumor toxicity.
Cellectis (NASDAQ: CLLS) ha pubblicato un articolo su Molecular Therapy che illustra il loro innovativo approccio SMART DUAL CAR T-cell per il trattamento dei tumori solidi. Utilizzando la tecnologia di editing genetico TALEN®, Cellectis ha sviluppato CAR T-cells allogeniche che esprimono:
1. Un CAR costitutivo che mira ai fibroblasti associati ai tumori (CAFs) FAP+ nei tumori solidi
2. Un CAR inducibile, espresso solo in presenza di CAFs FAP+, che mira alla mesotelina
Questa strategia punta a superare le sfide nel trattamento dei tumori solidi, tra cui la scarsa infiltrazione delle cellule T, l'ambiente microscopico immunosoppressivo e la tossicità on-target off-tumor. Nei modelli murini, queste CAR T-cell SMART Dual hanno infiltrato e mirato in modo efficiente ai tumori triplo-negativi al seno senza tossicità osservabile al di fuori del tumore.
Cellectis (NASDAQ: CLLS) ha publicado un artículo en Molecular Therapy que presenta su innovador enfoque SMART DUAL CAR T-cell para el tratamiento de tumores sólidos. Utilizando la tecnología de edición genética TALEN®, Cellectis ha desarrollado CAR T-cells alogénicas que expresan:
1. Un CAR constitutivo que se dirige a los fibroblastos asociados al cáncer (CAFs) FAP+ en tumores sólidos
2. Un CAR inducible, expresado solo en presencia de CAFs FAP+, dirigido a la mesotelina
Esta estrategia tiene como objetivo superar los desafíos en el tratamiento de tumores sólidos, incluido el bajo infiltrado de células T, el microambiente inmunosupresor y la toxicidad on-target off-tumor. En modelos de ratones, estas CAR T-cells SMART Dual infiltraron y dirigieron de manera eficiente a los tumores de mama triple negativos sin toxicidad observable fuera del tumor.
Cellectis(NASDAQ: CLLS)는 Molecular Therapy에 혁신적인 SMART DUAL CAR T-cell 접근 방식을 통해 고형종양 치료를 위한 논문을 발표했습니다. TALEN® 유전자 편집 기술를 활용하여 Cellectis는 다음을 발현하는 동종 CAR T세포를 개발했습니다:
1. 고형 종양 내 FAP+ 암 관련 섬유아세포(CAFs)를 표적으로 하는 지속적인 CAR
2. FAP+ CAFs가 존재할 때만 발현되는 유도 CAR로, 메소텔린을 표적으로 합니다.
이 전략은 낮은 T세포 침투, 면역 억제 미세환경, 그리고 목표 공격 외 종양 독성 같은 고형 종양 치료의 과제를 극복하는 것을 목표로 합니다. 생쥐 모델에서 이 SMART Dual CAR T세포는 관찰 가능한 외부 종양 독성 없이 효과적으로 침투하고 삼중 음성 유방 종양을 표적으로 했습니다.
Cellectis (NASDAQ: CLLS) a publié un article dans Molecular Therapy présentant leur approche innovante SMART DUAL CAR T-cell pour le traitement des tumeurs solides. En utilisant la technologie d'édition génique TALEN®, Cellectis a développé des CAR T-cells allogéniques qui expriment :
1. Un CAR constitutif ciblant les fibroblastes associés aux cancers (CAFs) FAP+ dans les tumeurs solides
2. Un CAR inductible, exprimé uniquement en présence de CAFs FAP+, ciblant la mésothelin
Cette stratégie vise à surmonter les défis liés au traitement des tumeurs solides, notamment la faible infiltration des cellules T, le microenvironnement immunosuppresseur et la toxicité on-target off-tumor. Dans des modèles murins, ces CAR T-cells SMART Dual ont efficacement infiltré et ciblé des tumeurs du sein triple-négatives sans toxicité observable hors du tumor.
Cellectis (NASDAQ: CLLS) hat einen Artikel in Molecular Therapy veröffentlicht, der ihren innovativen Ansatz SMART DUAL CAR T-cell zur Behandlung von soliden Tumoren präsentiert. Durch den Einsatz der TALEN®-Gentechnologie hat Cellectis allogene CAR T-Zellen entwickelt, die Folgendes exprimieren:
1. Ein konstitutives CAR, das FAP+ krebsassoziierte Fibroblasten (CAFs) in soliden Tumoren anspricht
2. Ein induzierbares CAR, das nur in Anwesenheit von FAP+ CAFs exprimiert wird und mesothelin anspricht
Diese Strategie zielt darauf ab, Herausforderungen in der Behandlung von soliden Tumoren zu überwinden, einschließlich niedriger T-Zell-Infiltration, immunologisch unterdrückendem Mikroumfeld und on-target off-tumor Toxizität. In Mäusemodellen infiltrierten und zielten diese SMART Dual CAR T-Zellen effizient auf triple-negative Brusttumoren ohne beobachtbare off-tumor Toxizität.
- Innovative SMART DUAL CAR T-cell approach for treating solid tumors
- Efficient targeting of triple-negative breast tumors in mice models
- No observable on-target, off-tumor toxicity in preclinical studies
- Potential to overcome key challenges in solid tumor CAR T-cell therapy
- Results are based on preclinical studies, clinical efficacy in humans yet to be proven
- Solid tumors remain challenging targets for CAR T-cell therapy
Insights
This publication in Molecular Therapy showcases Cellectis' innovative approach to tackling solid tumors, a significant challenge in CAR T-cell therapy. The SMART DUAL CAR T-cell design addresses key limitations: tumor infiltration, immunosuppressive microenvironment and on-target off-tumor toxicity. By targeting both FAP+ cancer-associated fibroblasts (CAFs) and the tumor antigen mesothelin, this approach could potentially improve efficacy and safety in solid tumor treatment.
The use of TALEN® gene editing to create an inducible CAR system is particularly clever, as it may reduce off-tumor effects. While promising, it's important to note that this research is still preclinical. The true test will be in human trials, where we'll see if these engineered T-cells can overcome the complex barriers of solid tumors in patients. If successful, this could significantly expand the application of CAR T-cell therapy beyond hematological cancers.
Cellectis' SMART DUAL CAR T-cell approach is an intriguing development in solid tumor immunotherapy. The strategy of targeting FAP+ cancer-associated fibroblasts (CAFs) to modulate the tumor microenvironment, combined with an inducible CAR for the tumor antigen mesothelin, is scientifically sound. This dual-targeting method could potentially address the heterogeneity of solid tumors and the immunosuppressive microenvironment, two major hurdles in current CAR T-cell therapies.
The reported efficacy against triple-negative breast tumors in mouse models is encouraging, but caution is warranted. Many promising preclinical results fail to translate to human studies. The key will be whether this approach can demonstrate similar efficacy and safety in clinical trials, particularly in managing potential cytokine release syndrome or neurotoxicity. If successful, this could represent a significant advance in solid tumor treatment, potentially expanding CAR T-cell therapy beyond its current indications.
NEW YORK, Aug. 26, 2024 (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, today published an article in Molecular Therapy demonstrating TALEN®-mediated gene editing capabilities for design of SMART DUAL CAR T-cells, which efficiently target immunotherapy recalcitrant solid tumors while mitigating potential safety risks.
Adoptive cell therapy based on CAR T cells has proven to be lifesaving for many cancer patients. However, its therapeutic efficacy has so far been restricted to only a few malignancies, with solid tumors proving to be especially recalcitrant to efficient therapy.
One key factor for this are cancer-associated fibroblasts (CAFs), that modulate the tumor microenvironment (TME) to inhibit T cell infiltration and induce T cell dysfunction. Additionally, the sparsity of tumor-specific antigens (TSA) and expression of CAR-directed tumor-associated antigens (TAA) on normal tissues often results in on-target off-tumor cytotoxicity, raising safety concerns.
Using TALEN® gene editing technology, Cellectis presents an innovative CAR T cell engineering strategy designed to overcome these challenges. Our allogeneic SMART CAR T-cells are designed to express a constitutive CAR, targeting FAP+ CAFs in solid tumors, and a second inducible CAR, expressed only in the presence of FAP+ CAFs and targeting the tumor associated antigen (TAA) named mesothelin. The resultant SMART Dual CAR T-cells efficiently infiltrate and efficiently target triple-negative breast tumors in physiologically relevant mice models, with no observable on-target, off-tumor toxicity.
“The adaptations of this approach could resolve several key challenges for CAR T-cell therapy against solid tumor-low CAR T-cell infiltration, immuno-suppressive microenvironment, antigen heterogeneity as well as on target, off-tumor toxicity. This strategy thus has significant implications for successful therapeutic development of CAR T-cells against solid tumors” said Shipra Das, Ph.D., Associate Director Immuno-Oncology and Innovation Program Management at Cellectis.
The article is available on Molecular Therapy website by clicking on this link: https://www.sciencedirect.com/science/article/pii/S1525001624005409?utm_campaign=STMJ_219742_AUTH_SERV_PA&utm_medium=email&utm_acid=300123771&SIS_ID=&dgcid=STMJ_219742_AUTH_SERV_PA&CMX_ID=&utm_in=DM500444&utm_source=AC_
About Cellectis
Cellectis is a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies. Cellectis 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 make therapeutic gene editing in hemopoietic stem cells for various diseases. As a clinical-stage biopharmaceutical company with 25 years of experience and expertise in gene editing, Cellectis is developing life-changing product candidates utilizing TALEN®, its gene editing technology, and PulseAgile, its pioneering electroporation system to harness the power of the immune system in order to treat diseases with unmet medical needs. Cellectis’ headquarters are in Paris, France, with locations in New York, New York and Raleigh, North Carolina. Cellectis is listed on the Nasdaq Global Market (ticker: CLLS) and on Euronext Growth (ticker: ALCLS).
Forward-looking Statements
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 “designed to,” and “could” or the negative of these and similar expressions. These forward-looking statements, which 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 research and development programs of the Company. 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 biopharmaceutical product candidate development. With respect to our cash runway, our operating plans, including product development plans, may change as a result of various factors, including factors currently unknown to us. Furthermore, many other important factors, including those described in our Annual Report on Form 20-F and the 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, 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, Interim Chief Financial Officer, +1 (347) 809 5980, investors@cellectis.com
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FAQ
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