विवरण
CAR T-cell therapy is a groundbreaking approach in cancer gene therapy that harnesses a patient’s immune cells to target and destroy cancer cells. In this technique, T-cells are genetically modified to express chimeric antigen receptors (CARs) that specifically recognize cancer cells. Once reintroduced into the patient, these CAR T-cells seek out and eliminate cancer cells with high precision. This therapy has shown remarkable success in treating certain types of blood cancers, such as leukemia and lymphoma, and is being explored for solid tumors. CAR T-cell therapy offers a promising personalized treatment, with ongoing research aimed at enhancing its safety, effectiveness, and applicability to a wider range of cancers.
सारांश
- The speaker introduces their diagnostics portfolio, highlighting liquid biopsy as the flagship product, alongside therapeutic efforts focused on immuno-oncology, particularly cell-based immunotherapies like CAR-T cells. Other therapies mentioned include CAR-NK cells, macrophages, T-regs, and tumor-infiltrating lymphocytes, but the main focus is on CAR-T cells due to their clinical approval and market presence.
- Cancer immunotherapy hinges on understanding the tumor microenvironment, categorizing tumors as "hot" (T-cell infiltration, immunotherapy benefits) or "cold" (no immune recognition, poor responders). Success stories are mainly in hot tumors, while cold tumors pose challenges. Strategies for cold tumors involve exposing antigens through mRNA-based therapies and oncolytic viruses.
- Tumor heterogeneity is significant, with drug-sensitive clones being killed by treatments, leaving resistant clones that contribute to minimal residual disease (MRD). Hot tumors are characterized by CD4 and CD8 positive T-cell infiltration, along with regulatory T-cells (T-regs) and M features. Liquid biopsy is presented as a sensitive tool for monitoring patients, particularly for MRD.
- Conventional pathology through biopsy is insufficient for comprehensive monitoring of tumors. Liquid biopsy provides a means to understand patient suitability for expensive immunotherapies with toxicities. It involves whole blood collection, plasma extraction, circulating tumor DNA sequencing, and utilizes Nano Pro sequencing for epigenetic changes and fragment distributions without PCR.
- T-cells, NK cells, macrophages, and tumors engage in crosstalk, and immune checkpoint inhibitors (PD-1, PDL-1) are utilized. Tumors employ "do not eat me" signals to evade the immune system and suppress T-cells. The speaker reviews the history of CAR-T cell therapy, noting the progression from first-generation cells (limited success) to second-generation (significant improvement) and third-generation cells.
- CAR-T cell therapy involves modifying T-cells with artificial receptors targeting tumor antigens. While cd19 is a common target, there is a trend toward specific biomarkers to only kill tumor cells. The fifth generation mainly involves on-off switch mechanisms and other forms of control to regulate activity and prevent toxicity.
- Miltenyi Biotec's CliniMACS Prodigy system is highlighted for CAR-T cell manufacturing. The closed, automated system facilitates T-cell isolation, transduction, and expansion. The entire process takes roughly 14-21 days and uses centrifugal incubation.
- Flow cytometry, using reagents from Miltenyi, is crucial for monitoring cell populations and activation markers (CD69, CD25). CFSE is used to measure proliferation, and the company also offers antibodies that provide good signal and binding quality. Miltenyi also has expansion agents.
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