Anti-ctla4 car t cell: auxiliary treatment in cancers
Alieh Fazeli,
1 Mehran bahreini,
2 Gholam hossein tammadon,
3,*
1. Shiraz university of medical sciences
2. Iran university of medical sciences
3. Shiraz university of medical sciences
Abstract
Introduction
Based on this point that some of cancers do not respond well to conventional therapy or the possibility of the relapse, immunotherapy is currently under investigation. this is also potentially reduces systemic toxicities and late effects. one of its new branches is treatment with t cells that change their receptor(car t cell). the research on these cells is generally according to design a receptor against a specific tumor antigen. but this review attempts to show that by targeting the treg, as an important immune cell in the tumor microenvironment, can see good effects.
Methods
This review article has been prepared with electronic search based on key words related with the aim of this paper. we use the scientific databases such as scholar, pubmed, science direct, medline and springer. almost all the articles that were used, are for the last 5 years.
Results
According to the studies, changes in tumor environment which inhibits immunsystem are caused the proliferation of malignant cells. one of the immune cells that are beneficial for the progression of the tumor is treg. for this purpose, car t cell is recommended to be designed. at first the leukocytes must be collected by leukopheresis method and then t cell isolated to design car t on them. car is a construct that expresses the receptor against a specific antigen in the tumor. it is difficult way to car t cell design so tils can be isolated from the beginning using existing methods. then these cells are grown in vitro and they will have a receptor against the tumor antigen and will therefore directly affect them. anti-ctla4 receptor in tils alone or in conjunction with an anti-nrp1 receptor are placed which requires their simultaneous expression in tils so that only special types of them that do not produce ifn-γ are detected. in addition to the above mentioned, a receptor ccr4 anti-chemokine ccl17, ccl22 within the tumor environment is reguired. after that, cloning and transferring to lentiviruses,then transferring this anti-ctla4 and anti-nrp1 to memory t cd8 + must be done. functionality, cytotoxicity, persistanse and prolifration assay should be evaluated. finally this car t into a patient with a solid tumor injected and simultaneous an anti-pd1 antibody or other drugs that is needed, administered.
Conclusion
Tumor environment factors can be the most important factors in the progression of tumor, metastasis, and suppression of immunity and resistance therapies. therefore, in the method therapeutic care should pay attention to the tumor environment. chemokines are also important factors that can influence tumor immune cell infiltration and regulate angiogenesis, proliferation, and survival of tumor cells. the targeting of chemokines, if accompanied by existing treatments for cancer, can have synergistic effects for immune responses. there are new methods of immunotherapy, including the use of checkpoint inhibitors, bispecific antibodies, and car t cell, each of which can be used in certain conditions.
in this review, we try to introduce the effective methods with respect to the tumor and its environment, as a new type of car t cell that will have higher efficacy.
many characteristics of the car t cell, such as its sustainability, are being investigated. to improve the stability of t and overcome the t cell exhaustion, it can be used t memory that has better stability and the patient is protected for a longer period against recurring diseases. il-15 and il-12 result in memory phenotypes and increased susceptibility. checkpoint inhibitors against pd1-pdl1 or ctla4 can also be used to further stabilize the t cell within the body. in this study, it is also thought that durability of car t may be high due to the use of t-memory and drug-resistant checkpoint. also toxicity would decrease significantly when the icas9 system was designed to prevent the hyperactivation of t cells. because of the bi-specificity of the receptor, the probability of binding to the non-specific antigen was low.
of course, some of the problems with such a treatment are definitely its design, that its probably a lot of cost, because there are certainly many problems with the many factors involved in making a drug.
Keywords
Chimeric antigen receptor, immunotherapy, regulatory t cell, ctla4
