Cellectis Unveils Innovative SMART DUAL CAR T-cell Therapy
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Cellectis Unveils Innovative SMART DUAL CAR T-cell Therapy
Cellectis (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company, has recently published an article highlighting a groundbreaking approach in the realm of cell and gene therapies. This publication details the company's SMART DUAL CAR T-cell strategy, which utilizes TALEN® gene editing technology to address the ongoing challenges faced in treating recalcitrant solid tumors. The innovative design of these CAR T-cells targets resistant tumor types while significantly mitigating safety concerns.
Understanding the Recalcitrance of Solid Tumors
Adoptive cell therapy, particularly CAR T-cell therapy, has been a lifeline for numerous cancer patients. However, the application of this therapy has predominantly been limited to specific malignancies, with solid tumors proving particularly difficult to treat. Several factors hinder the effective targeting of these tumors, notably the role of cancer-associated fibroblasts (CAFs).
CAFs play a pivotal role in creating a tumor microenvironment (TME) that restricts T cell infiltration and promotes T cell dysfunction. The absence of tumor-specific antigens (TSAs), coupled with tumor-associated antigens (TAAs) being expressed on normal tissues, often leads to on-target off-tumor cytotoxicity. This raises significant safety concerns that can deter the effective application of traditional CAR T-cell therapies.
Innovative CAR T-cell Engineering Strategy
Cellectis' SMART DUAL CAR T-cell technology is designed to overcome these limitations. Utilizing TALEN® gene editing technology, the company has engineered allogeneic SMART CAR T-cells with dual targeting capabilities. These T-cells express a constitutive CAR that specifically targets FAP+ CAFs found within solid tumors. Additionally, they incorporate an inducible CAR that activates only in the presence of FAP+ CAFs, targeting the tumor-associated antigen mesothelin.
This dual-targeting approach has shown promising results. In preclinical models, SMART Dual CAR T-cells demonstrated a remarkable ability to infiltrate and effectively target triple-negative breast tumors, with no detectable instances of on-target off-tumor toxicity. These findings suggest a significant leap forward in the quest for effective therapies against solid tumors.
Implications for Future Cancer Therapies
Dr. Shipra Das, Associate Director of Immuno-Oncology and Innovation Program Management at Cellectis, remarked on the potential of this strategy. "This approach could effectively address several critical issues associated with CAR T-cell therapy for solid tumors, such as low CAR T-cell infiltration, immunosuppressive microenvironments, antigen heterogeneity, and safety concerns regarding on-target off-tumor cytotoxicity. It holds considerable promise for the successful therapeutic development of CAR T-cells targeted towards solid tumors," she stated.
About Cellectis
Cellectis is a pioneering clinical-stage biotechnology company dedicated to creating transformative cell and gene therapies. Leveraging their advanced gene-editing platform, Cellectis focuses on developing off-the-shelf, allogeneic CAR T-cell therapies aimed at treating various cancers. The company is at the forefront of therapeutic gene editing in hematopoietic stem cells, showcasing its commitment to addressing unmet medical needs with innovative solutions.
With a strong foundation of 25 years of expertise in gene editing, Cellectis continues to utilize its TALEN® technology and the PulseAgile electroporation system. This commitment to harnessing the immune system's power reflects the company’s goal to revolutionize cancer treatment and improve patient outcomes. Cellectis maintains its headquarters in Paris, France, with additional offices in New York and Raleigh.
Frequently Asked Questions
What is the SMART DUAL CAR T-cell approach?
The SMART DUAL CAR T-cell approach involves engineering CAR T-cells to target specific cancer-associated fibroblasts while also allowing for the targeting of tumor-associated antigens in a highly selective manner, reducing potential safety risks.
Why are solid tumors difficult to treat with CAR T-cell therapy?
Solid tumors present challenges due to the immunosuppressive tumor microenvironment, low levels of tumor-specific antigens, and the presence of tumor-associated antigens on normal tissues, which can lead to off-target effects.
What technology does Cellectis use for gene editing?
Cellectis employs TALEN® gene editing technology to engineer its CAR T-cells, enabling the creation of precise and effective therapeutic candidates targeting solid tumors.
How does the inducible CAR work in the SMART Dual CAR T-cell?
The inducible CAR is activated only in the presence of specific markers on CAFs, allowing targeted therapy that minimizes the potential for damage to surrounding healthy tissues.
What are Cellectis' main objectives in gene therapy?
Cellectis aims to develop effective and innovative cell and gene therapies that improve patient outcomes by addressing unmet medical needs and enhancing cancer treatment options.
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