Details

Autor(en) / Beteiligte

• Moghanloo, Ehsan
• Mollanoori, Hasan
• Talebi, Mohsen
• Pashangzadeh, Salar
• Faraji, Fatemeh
• Hadjilooei, Farimah
• Mahmoodzadeh, Habibollah

Titel

Remote controlling of CAR-T cells and toxicity management: Molecular switches and next generation CARs

Ist Teil von

• Translational oncology, 2021-06, Vol.14 (6), p.101070, Article 101070

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• •The emergence of CAR-T cell therapy with its exciting results attained in patients with relapsed and refractory hematological malignancies is considered as the biggest advance in cellular cancer immunotherapy. However, severe side effects and toxicity stir concerns regarding the safety of CAR-T cell treatments.Most of CAR-T cell therapies are currently autologous small-scale treatments for patients suffering from B cell malignancies due to the safety concerns about the potential development of a GVHD in allogeneic therapies. So, allogeneic therapies have been less effective than autologous ones. High cost and highly variable manufacturing processes are other limitations on the way of CAR-T cell therapy. In contrast to the unprecedented responses achieved through using CD19-CAR-T cells in the treatment of ALL, this type of treatment has not shown the same results in the battle against solid tumors that is partly related to different characteristics and microenvironment of solid tumors that limit the success of CAR-T cell therapies in patients with solid tumors. Immune checkpoint therapies with previously reported reproducible beneficial effects in 20–30% of patients with different incurable cancers have serious side effects and considerable cost of repeated administration. Also, recently most patients have not responded effectively to these therapies. In contrast, CAR-T cell therapy has two characteristics that may compensate for the limitations of immune checkpoint therapies. Firstly, only one administration of the engineered T cells is needed for long lasting effectiveness of the therapy. Secondly, more than 90% of patients suffering from ALL respond to CAR-T cell therapy, a result which is not obtained through administration of the immune checkpoints. Future development of CAR-T cell technology should address concerns related to the safety of the treatment and improve toxicity management. Also, it should extend the application of technology in diseases where its effectiveness has been demonstrated and opt for more targets and cancers. Cell-based immunotherapies have been selected for the front-line cancer treatment approaches. Among them, CAR-T cells have shown extraordinary effects in hematologic diseases including chemotherapy-resistant acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (NHL). In this approach, autologous T cells isolated from the patient's body genetically engineered to express a tumor specific synthetic receptor against a tumor antigen, then these cells expanded ex vivo and re-infusion back to the patient body. Recently, significant clinical response and high rates of complete remission of CAR T cell therapy in B-cell malignancies led to the approval of Kymriah and Yescarta (CD19-directed CAR-T cells) were by FDA for treatment of acute lymphoblastic leukemia and diffuse large B-cell lymphoma. Despite promising therapeutic outcomes, CAR T cells also can elicit the immune-pathologic effects, such as Cytokine Release Syndrome (CRS), Tumor Lysis Syndrome (TLS), and on-target off-tumor toxicity, that hampered its application. Ineffective control of these highly potent synthetic cells causes discussed potentially life-threatening toxicities, so researchers have developed several mechanisms to remote control CAR T cells. In this paper, we briefly review the introduced toxicities of CAR-T cells, then describe currently existing control approaches and review their procedure, pros, and cons.