Car-T Hücre Tedavi Sistemi
Authors: Batar Bahadır , Çeker Dilek Demircan , Turgut Burhan , Yılmaz Ahsen Morva , Oran Mustafa , Tekin Şaban , Karadağ Abdullah 
Published: April 2023

The growth, survival, and spread of cancer cells evolve depending on the interaction with the surrounding microenvironment (TME). The primary treatment option for many early-stage cancers includes conventional methods such as surgery or radiotherapy. However, in recent years, chemotherapy, newly designed biological agents, and immunotherapy strategies have been preferred for late-stage cancers characterized by non-controlled cell dissemination. Nowadays, conventional therapy options have been gradually replaced by targeted biological agents and immunotherapy methods to cure hematological malignancies such as leukemia, lymphoma, and multiple myeloma. In most cancers, resistance develops over time against chemotherapeutic and biological agents, and thus, the prognosis is adversely affected. Recently, cell-based therapies targeting the immune system by the infusion of monoclonal antibody-based biopharmaceuticals became popular and an effective alternative treatment option for patients resistant to conventional methods. One of the next-generation therapeutic approaches with minimum side effects and maximum safety is the creation of a genetically engineered chimeric antigen receptor (CAR) on T cells within a synthetic biology approach. CAR-T cells carrying the engineered receptor against a specific tumor antigen were first tested in hematological malignancies and presented encouraging results. During the development process, CAR structures were updated with costimulatory agents such as CD28, 4-IBB, OX-40, and cytokine supplements such as IL-2, IL-7, IL-15 to provide a long-term immune response. The molecular structure of the CAR-T receptor, immunological characterization of CAR-T cells, and post-infusion side effects are the key parameters to be considered for clinical validation of this product. In addition to the GMP requirement, the potency, safety, purity, and authentication steps based on the relevant guidelines are imperatives to validate the drug candidate for high-quality production. CAR-T treatment has been applied with satisfaction to patients presenting an advanced stage profile or with cancer recurrence, developing significant drug resistance, and having limited treatment options. However, toxic side effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, which are compatible with the post-infusion morbidity/mortality rate, especially in the first period applications have also been reported. Due to the improvements made in the CAR structure over time, control of these side-effects and life extension of CAR-T cells are relatively performable. CAR-T cell production technology, which has left its infancy behind, is considered a groundbreaking improvement option in cancer treatment. However, personalized CAR-T cell therapy is a costly system. Efforts continue intensively to reduce costs to the levels that healthcare systems can afford. Despite several financial and medical obstacles, the field of CAR-based immune cells offers promising results and will undoubtedly gain a well-supported place among the new generation treatment systems.