Programmable and multi-targeted CARs: a new breakthrough in cancer CAR-T cell therapy

CAR-T cell therapy, as a novel immunotherapy approach, has indicated successful results in the treatment of hematological malignancies; however, distinct results have been achieved regarding solid tumors. Tumor immunosuppressive microenvironment has been identified as the most critical barrier in CAR-T cell therapy of solid tumors. Developing novel strategies to augment the safety and efficacy of CAR-T cells could be useful to overcome the solid tumor hurdles. Similar to other cancer treatments, CAR-T cell therapy can cause some side effects, which can disturb the healthy tissues. In the current review, we will discuss the practical breakthroughs in CAR-T cell therapy using the multi-targeted and programmable CARs instead of conventional types. These superior types of CAR-T cells have been developed to increase the function and safety of T cells in a controllable manner, which would diminish the incidence of relevant side effects. Moreover, we will describe the capability of these powerful CARs in targeting multiple tumor antigens, redirecting the CAR-T cells to specific target cells, incrementing the safety of CARs, and other advantages that lead to promising outcomes in cancer CAR-T cell therapy (AU)

Programmable and multi-targeted CARs: a new breakthrough in cancer CAR-T cell therapy.

CAR-T cell therapy, as a novel immunotherapy approach, has indicated successful results in the treatment of hematological malignancies; however, distinct results have been achieved regarding solid tumors. Tumor immunosuppressive microenvironment has been identified as the most critical barrier in CAR-T cell therapy of solid tumors. Developing novel strategies to augment the safety and efficacy of CAR-T cells could be useful to overcome the solid tumor hurdles. Similar to other cancer treatments, CAR-T cell therapy can cause some side effects, which can disturb the healthy tissues. In the current review, we will discuss the practical breakthroughs in CAR-T cell therapy using the multi-targeted and programmable CARs instead of conventional types. These superior types of CAR-T cells have been developed to increase the function and safety of T cells in a controllable manner, which would diminish the incidence of relevant side effects. Moreover, we will describe the capability of these powerful CARs in targeting multiple tumor antigens, redirecting the CAR-T cells to specific target cells, incrementing the safety of CARs, and other advantages that lead to promising outcomes in cancer CAR-T cell therapy.

E3 ubiquitin ligase Casitas B lineage lymphoma-b and its potential therapeutic implications for immunotherapy.

The distinction of self from non-self is crucial to prevent autoreactivity and ensure protection from infectious agents and tumors. Maintaining the balance between immunity and tolerance of immune cells is strongly controlled by several sophisticated regulatory mechanisms of the immune system. Among these, the E3 ligase ubiquitin Casitas B cell lymphoma-b (Cbl-b) is a newly identified component in the ubiquitin-dependent protein degradation system, which is thought to be an important negative regulator of immune cells. An update on the current knowledge and new concepts of the relevant immune homeostasis program co-ordinated by Cbl-b in different cell populations could pave the way for future immunomodulatory therapies of various diseases, such as autoimmune and allergic diseases, infections, cancers and other immunopathological conditions. In the present review, the latest findings are comprehensively summarized on the molecular structural basis of Cbl-b and the suppressive signaling mechanisms of Cbl-b in physiological and pathological immune responses, as well as its emerging potential therapeutic implications for immunotherapy in animal models and human diseases.