Cellectis Presents Pre-Clinical Evidence of MUC1 CAR T-cells Reducing Triple-Negative Breast Cancer While Preserving Safety
Cellectis, a clinical-stage biotechnology company, has published a scientific article in Science Advances showcasing promising pre-clinical results for treating triple-negative breast cancer (TNBC) using TALEN®-edited MUC1 CAR T-cells. The study demonstrates that multi-armored CAR T-cells, engineered with PD1KO, tumor-specific IL12 release, and TGFBR2KO attributes, showed enhanced cytotoxic activity against TNBC in mouse models.
Notably, intratumoral treatment effectively reduced both local and distant tumors using low doses of the engineered CAR T-cells, suggesting potential efficacy against metastasis. The research highlights the capabilities of multiplex editing in improving both efficacy and safety of CAR T-cell therapies for solid tumors, offering hope for advanced-stage TNBC patients with treatment options.
Cellectis, un'azienda biotecnologica in fase clinica, ha pubblicato un articolo scientifico su Science Advances che presenta risultati preclinici promettenti per il trattamento del carcinoma mammario triplo negativo (TNBC) utilizzando cellule CAR T modificati con TALEN® per MUC1. Lo studio dimostra che le cellule CAR T multi-armate, ingegnerizzate con caratteristiche di PD1KO, rilascio tumorale specifico di IL12 e TGFBR2KO, hanno mostrato attività citotossica potenziata contro il TNBC in modelli murini.
In particolare, il trattamento intratumorale ha ridotto efficacemente sia i tumori locali che quelli distanti utilizzando basse dosi delle cellule CAR T ingegnerizzate, suggerendo un potenziale di efficacia contro la metastasi. La ricerca evidenzia le capacità dell'editing multiplex nel migliorare sia l'efficacia che la sicurezza delle terapie con cellule CAR T per tumori solidi, offrendo speranza ai pazienti con TNBC in stadio avanzato riguardo alle opzioni di trattamento.
Cellectis, una empresa biotecnológica en etapa clínica, ha publicado un artículo científico en Science Advances que muestra resultados preclínicos prometedores para tratar el cáncer de mama triple negativo (TNBC) utilizando células CAR T editadas con TALEN® para MUC1. El estudio demuestra que las células CAR T multilaterales, ingeniadas con características de PD1KO, liberación de IL12 específica del tumor y TGFBR2KO, mostraron actividad citotóxica mejorada contra el TNBC en modelos de ratón.
Notablemente, el tratamiento intratumoral redujo efectivamente tanto los tumores locales como los distantes utilizando dosis bajas de las células CAR T ingenierizadas, lo que sugiere una potencial eficacia contra la metástasis. La investigación destaca las capacidades de la edición multipunta para mejorar tanto la eficacia como la seguridad de las terapias con células CAR T para tumores sólidos, ofreciendo esperanza a los pacientes con TNBC en etapa avanzada con opciones de tratamiento.
Cellectis는 임상 단계의 생명공학 회사로, TALEN®로 편집된 MUC1 CAR T 세포를 사용하여 삼중 음성 유방암 (TNBC) 치료를 위한 유망한 전임상 결과를 보여주는 과학 기사를 Science Advances에 발표했습니다. 이 연구는 PD1KO, 종양 특이적 IL12 방출, TGFBR2KO 속성을 가진 다중 장착 CAR T 세포가 생쥐 모델에서 TNBC에 대한 향상된 세포 독성 활성을 보였음을 입증합니다.
특히, 종양 내 치료는 저용량의 엔지니어링된 CAR T 세포를 사용하여 국소 및 원거리 종양을 효과적으로 감소시켰으며, 전이 방지에 대한 잠재적인 효능을 나타냅니다. 이 연구는 고형 종양에 대한 CAR T 세포 치료의 효과와 안전성을 개선하기 위한 다중 편집의 능력을 강조하며, 진행 단계의 TNBC 환자에게 치료 옵션을 제공하는 희망을 제시합니다.
Cellectis, une entreprise de biotechnologie en phase clinique, a publié un article scientifique dans Science Advances présentant des résultats précliniques prometteurs pour le traitement du cancer du sein triple négatif (TNBC) à l'aide de cellules CAR T éditées avec TALEN® pour MUC1. L'étude démontre que les cellules CAR T multi-armées, ingénierées avec des caractéristiques de PD1KO, de libération spécifique de l'IL12 et de TGFBR2KO, ont montré une activité cytotoxique améliorée contre le TNBC dans des modèles murins.
Notamment, le traitement intratumoral a réduit efficacement à la fois les tumeurs locales et distantes en utilisant de faibles doses de cellules CAR T modifiées, ce qui suggère un potentiel d'efficacité contre les métastases. La recherche souligne les capacités de l'édition multiplex dans l'amélioration à la fois de l'efficacité et de la sécurité des thérapies CAR T pour les tumeurs solides, offrant de l'espoir aux patients à un stade avancé de TNBC concernant les options de traitement.
Cellectis, ein biopharmazeutisches Unternehmen in der klinischen Phase, hat einen wissenschaftlichen Artikel in Science Advances veröffentlicht, der vielversprechende präklinische Ergebnisse für die Behandlung von dreifach negativem Brustkrebs (TNBC) mit TALEN®-bearbeiteten MUC1 CAR-T-Zellen zeigt. Die Studie zeigt, dass mehrarmige CAR-T-Zellen, die mit PD1KO, tumor-spezifischer IL12-Freisetzung und TGFBR2KO-Merkmalen ausgestattet sind, verbesserte zytotoxische Aktivität gegen TNBC in Mausmodellen zeigten.
Bemerkenswerterweise reduzierte die intratumorale Behandlung sowohl lokale als auch distale Tumoren effektiv durch die Verwendung von niedrigen Dosen der konstruierten CAR-T-Zellen, was auf ein potenzielles Ansprechen gegen Metastasen hindeutet. Die Forschung hebt die Fähigkeiten der Multiplex-Bearbeitung zur Verbesserung sowohl der Wirksamkeit als auch der Sicherheit von CAR-T-Zelltherapien für solide Tumoren hervor und bietet Hoffnung für Patienten mit fortgeschrittenem TNBC hinsichtlich von Behandlungsmöglichkeiten.
- Pre-clinical evidence shows TALEN®-edited MUC1 CAR T-cells effectively reduce triple-negative breast cancer tumors
- Multi-armored CAR T-cells demonstrate enhanced cytotoxic activity in mouse models
- Intratumoral treatment effectively reduced both local and distant tumors using low doses
- Potential to address metastasis with local administration of CAR T-cells
- Unexpected cooperation between edits increased safety, highlighting multiplex editing capabilities
- None.
This pre-clinical study on MUC1 CAR T-cells for triple-negative breast cancer (TNBC) is a significant step forward in solid tumor immunotherapy. The research demonstrates enhanced efficacy through multi-layered engineering, including PD1KO, tumor-specific IL12 release and TGFBR2KO. Notably, the intratumoral administration showed promise in reducing both local and distant tumors, suggesting potential for metastasis treatment.
The study's innovative approach using TALEN®-mediated multiplex editing not only improved anti-tumor responses but also revealed unexpected safety benefits. This dual advantage could be a game-changer for TNBC patients who currently have treatment options. However, it's important to note that translating pre-clinical success to human trials often faces challenges and further research is needed to confirm these promising results in clinical settings.
The potential of MUC1 CAR T-cell therapy for TNBC is exciting, especially given the aggressive nature of this cancer subtype. The multi-armored approach addresses key challenges in solid tumor immunotherapy, particularly the immunosuppressive tumor microenvironment. The ability to reduce distant tumors with local administration is particularly promising for managing metastatic disease, a critical factor in TNBC prognosis.
However, we must temper enthusiasm with caution. While pre-clinical results are encouraging, the complex tumor biology in humans may present unforeseen challenges. The safety profile will be important to monitor in future clinical trials, as CAR T-cell therapies can have significant side effects. If successful, this approach could offer hope to TNBC patients who currently face and often ineffective treatment options.
Cellectis' advancement in CAR T-cell therapy for solid tumors could significantly impact the company's market position. The multi-armored approach and TALEN® gene-editing platform demonstrate Cellectis' innovative capabilities, potentially differentiating them in the competitive immuno-oncology field. The intratumoral administration method could also offer a unique selling point, possibly reducing treatment costs and improving patient outcomes.
However, investors should note that commercialization is still distant. The path from pre-clinical to approved therapy is long and costly, with many potential pitfalls. Cellectis will need substantial resources to progress this therapy through clinical trials. While this research enhances Cellectis' pipeline value, it's important to consider the company's financial position and ability to fund further development. The potential market for a successful TNBC therapy is substantial, but realization of this potential remains uncertain at this early stage.
NEW YORK, Sept. 03, 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 a scientific article in Science Advances suggesting that TALEN®-edited MUC1 CAR T-cells could be a potential treatment option for advance-stage triple negative breast cancer (TNBC) patients with limited therapeutic options.
Globally, breast cancer continues to be the most prevalent malignancy in women. Among all subtypes, triple-negative breast cancer (TNBC) stands out as the most aggressive form with high metastatic potential and poor survival rates.
Despite a few emerging targeted therapies under investigation, surgery, chemotherapy and radiation therapy continue to be the standard of care, and their success remains limited. As an alternative, Chimeric Antigen Receptor (CAR) T-cell therapies could hold promise for advance-stage TNBC patients as tumor-associated MUC1 antigen is overexpressed in a large number of patients thus offering a distinct target for treatment.
In this article, Cellectis described its multi-layered CAR T-cell engineering strategy using TALEN® and synthetic biology to multi-armor CAR T-cells with synergistic functionalities to overcome the immunosuppressive tumor microenvironment (TME) of solid tumors. With this strategy, Cellectis demonstrates enhanced cytotoxic activity of MUC1 CAR T-cells armored with PD1KO, tumor-specific IL12 release and TGFBR2KO attributes, all of them catered towards the TNBC TME, in intravenous and intratumoral mouse models.
“Complexity of solid tumors decreases the efficacy of CAR T-cell therapies. With this pre-clinical study, we showed that TALEN®-mediated multiplex editing can support CAR T-cells in effectively mounting an anti-tumor response to clear breast tumors, and that we can further decrease the dose of the treatment by injecting the CAR T cells intratumorally while still treating distant tumors. This innovative approach also allowed us to discover an unexpected cooperation between the edits in increasing safety, highlighting the potential capabilities of multiplex editing” said Piril Erler, PhD, Scientist II at Cellectis.
Importantly, intratumoral treatment effectively reduced local and distant tumors of large size using low doses of multi-armored MUC1 CAR T-cells. This pre-clinical data suggests that the benefits of antigen recognition are maintained at distant sites and highlights the potential to address metastasis with local administration.
The article is available on Science Advances’ website by clicking on this link: https://www.science.org/doi/10.1126/sciadv.adn9857
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).
To find out more, visit our website: www.cellectis.com
Follow Cellectis on social networks @cellectis on LinkedIn and X (formerly Twitter)
TALEN® is a registered trademark owned by Cellectis.
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 “"can,” “possibility,” and “suggest” 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, include statements about the potential of the product candidate MUC1, and reproducibility of these preclinical data on humans. 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. 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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