Description
Recent advancements in surgical approaches to oral cancer have emphasized precision and minimally invasive techniques. Robotic-assisted surgery and transoral laser microsurgery allow for enhanced accuracy, reducing damage to surrounding tissues. Surgeons also increasingly use image-guided technology, which enhances visualization and helps remove tumors more effectively. Sentinel lymph node biopsy has become a standard for early-stage oral cancer, enabling better staging with minimal invasiveness. These advancements contribute to faster recovery times, reduced complications, and improved overall outcomes for patients.
Résumé
- The speaker, who has a background in infectious diseases and cancer research, discusses CAR T-cell therapy as a rapidly evolving field. He mentions his involvement with companies like Therosys (now Onomics) and Epistem Genomics, highlighting their research in CAR T-cells. He clarifies his role as having taken an exit from the company but not a financial one, emphasizing the current struggles faced by startups, especially big ones like biocon. The company is currently looking for somebody to buy their intellectual property and as a temporary measure has merged with one of their another company Epistem Genomics.
- CAR T-cell therapy, a type of biologic therapy, involves genetically engineering a patient's T cells to target cancer cells. This differs from traditional small molecule pharmaceuticals and falls under the category of cell and gene therapies (CGT). The genetically engineered cells, known as living drugs, have unique properties that enable them to attack and destroy cancer cells. This approach is primarily used for hematological cancers (blood cancers) due to the availability of biomarkers like CD19, which is commonly expressed in B-cell malignancies.
- CAR T-cells are engineered using viral vectors, most commonly retroviruses and lentiviruses, to deliver the genetic material into the T cells. However, concerns about the potential for secondary cancers associated with viral integration have led to a push toward non-viral approaches. A typical CAR T-cell construct includes a single-chain variable fragment (ScFv) for target recognition, a hinge region for flexibility, a transmembrane domain, and cytoplasmic domains (e.g., 4-1BB from Kymriah and CD28 from Yescarta) for signaling and activation.
- The speaker notes that while viral vectors are convenient, there is concern of secondary cancers due to this and they wish to move to non-viral approach. Each component plays a crucial role in the CAR T-cell's ability to bind to cancer cells, activate the T cell, and initiate cell death. The cytoplasmic domains, derived from different proteins, simulate the immunological synapse, mimicking natural T cell activation. The selection of co-stimulatory domains like 4-1BB and CD28 impacts the duration and intensity of the T cell response, with 4-1BB providing a more sustained effect and CD28 offering a faster, quicker response.
- Approved CAR T-cell therapies, such as Kymriah and Yescarta, are primarily used for lymphomas and leukemias. CAR T cell therapy approvals are for B cell leukemias and lymphomas and the B cells only. The naming conventions for cell and gene therapies follow a specific pattern, with the brand name being easier to remember. While initially used as a last line of defense, CAR T-cell therapies are increasingly being considered as a first-line treatment for certain conditions.
- The speaker highlights the importance of minimizing pre-treatment with chemotherapy to ensure the T cells are not weakened before CAR T-cell engineering. He describes some reasons why the treamtment might fail and how the company is refunding to the patients in such cases. The success of CAR T-cell therapy is highly dependent on the patient's individual condition, and some patients respond better than others. The cost involved can be a barrier, this is why he suggests indigenous treatment is important to bring cost down.
- One of the main challenges of CAR T-cell therapy is cytokine release syndrome (CRS), an inflammatory response that can cause systemic organ damage. Treatments like tocilizumab, which targets IL-6, are used to manage CRS. Other potential issues include neurotoxicity and antigen loss, where the cancer cells alter their surface markers, rendering the CAR T-cells ineffective. Several strategies, including gamma delta T cells and regulatory T cells, are being explored to address these challenges.
- Future directions in CAR T-cell therapy include the development of armored CARs, which enhance the efficiency of the T cells, and the exploration of new target antigens beyond CD19 and BCMA. Additionally, researchers are investigating on/off switch mechanisms to control CAR T-cell activity and minimize toxicity. Other technological advances include mRNA in vivo technologies, using crisper technology to genetically modify the cells, making the treatment more effective and less costly and eliminating the need for taking out T cells from the body.
- Despite the success in treating blood cancers, CAR T-cell therapy faces significant challenges in solid tumors due to the immunosuppressive nature of the tumor microenvironment. New approaches, such as combining CAR T-cell therapy with immune checkpoint inhibitors, are being investigated to overcome this limitation. India is emerging as a potential manufacturing hub for cell and gene therapies, offering a cost-effective alternative to countries like the US and Europe, which are hesitant to work with China due to intellectual property concerns.
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À propos des intervenants
Dr Abhimanyu Kadapathri
Consultant en oncologie chirurgicale de la tête et du cou, hôpital Paras Yash Kothari, Kanpur
Divulgation financière
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