Chimeric antigen receptor CAR Technique - Creative Biolabs (Original Version)

hello everybody welcome to watch created by a lab video about immune system and immune therapy today we are going to share some basic knowledge about chimeric antigen receptor or car technology and its application on tumor therapy malignant tumor also known as cancer is one of the most deadly human diseases now with very high mortality and poor prognosis due to the higher current rate and metastasis normal cells will transform into tumor cells under the condition of gene damage or mutation at present there are several six strategies to treat cancer radioactive therapy and chemotherapy is conventional approach but both of them have obvious side effect due to the indiscriminate damage of normal cells for a large well-defined tumors surgically removal is a better choice however as there as is often as high recurrence rate due to the incompletely resection the latest idea is immunotherapy by artificially modulating and strengthening the patient's own immune system to target and eliminate tumor cells immunotherapy has great potential to cure cancer with very low side-effect anti-tumor elimination expectation to better understand how the immunotherapy works we should have some basic knowledge about our immune system there are mainly two different kinds of immune cells t-cells and b-cells they take in charge of cellular immunity and humoral immunity respectively among t-cells there are also two subtypes cd8 positive T cell and cd4 positive T cell cd8 positive T cell is also known as cytotoxic T cell it directly recognizes tumor cells and secrete cytokines to damage or cause programmed cell death of tumor cells cd4 positive T cell also named as helper T cell it help b-cell activate and differentiate into plasma cells which of the ability to massively produce antibodies to eliminate tumor cells these specific antibodies can target tumor cells and cause cell damage by a DCC effect or phagocytosis these are our immune system fight against tumor cells the ideas of immunotherapies including anti tumor monoclonal antibody drugs antibody drug conjugates as well as chimeric antigen receptor T or NK cells are basically based on the fundamentals of antibodies and cytotoxic cells since the immune system as the mechanism to surveil and clear tumor cells why do people still get cancer the reason is the tumor cells have multiple methods to avoid the immune surveillance and escape from being eliminated by our immune system immune escape mechanism is very complex to discuss such as immune suppressed tumor micro-environment antigen presenting cell disable down modulation of surface antigen presentation cd4 positive T cell tolerance and cd8 positive T cell dysfunction could all be involved in tumor escape process in brief we can simply believe that tumor cells have the ability to reduce the T cells recognition to avoid surveillance to better understand how tumor cells cause t-cell dysfunction we must know the TN tumor cell recognition mechanism firstly there are two different types of antigen presented on tumor cell surface 1 is membrane protein antigens which could be targeted by antibodies or b-cell receptors the other is peptide antigens which are presented with major histocompatibility complex molecule together as a complex and targeted by t-cell receptors t-cell recognize tumor cells is actually based on the recognition of t-cell receptor and peptide MHC complex in general TCR recognizes the presented peptide antigen of Taurus l as the first signalling along with other co-stimulatory molecules as binding such as cd28 and b7 as the second signalling this double signal pathway system leads to full activation of t-cell to kill tumor cells however tumor cells also of response actions such as down regulating the expression of specific peptide antigens down regulating the expression of MHC molecules and co-stimulatory molecules to inhibit t-cell recognition of tumor cells so that to avoid the immune attacks it is well known that the candidate markers recognized by antibody are much broader than those of TCR antibody recognition as MHC independent and it's binding affinity could be optimized by antibody affinity screening process in this case if we combine an antibody recognition domain with a TCR signaling motif to form a chimeric t-cell receptor it could form a more robust antigen receptor that has not only higher tumor recognition capability but also the ability to trigger T cell cytotoxicity effect this genetically engineered t-cell is what we call chimeric antigen receptor T cells or cart T technically there are several steps to construct a car T cell first of all an ideal target tumor antigen need to be chosen for affinity screening to identify the optimized antibody and obtain the gene sequence of selected antibody then according to the design of car construction car genes are synthesized and packaged into viral vectors after this car genes are delivered into T cells through virus transfection culture the trans genetic T cells and select those T cells with stable car expression finally test the quality of these newly created car T cells the proliferation ability car receptor expression cytotoxicity cytokine release an anti tumor function both in vitro and in vivo are all need to be evaluated and qualified before it can be used in clinical trials after years of development Carty technology has made great progress 'as the first generation car is simply constructed an antibody domain a single cd3 zeta domain this car t-cell only has a temporary anti-tumor activity the second generation car have an additional co-stimulatory signaling domains such as CT 28 or 41 BB to maintain a long-term effect compared to the first generation recent developments fuse the intracellular part of the second co-stimulatory molecules such as CM - in addition thus generating tripartite signaling car this third-generation car cells seem to have superior qualities such as higher level cytokine secretion significantly increased proliferation speed and survival rate the next-generation car will additionally be modified with a constitutive or inducible expression cassette for cytokines or herself withdrawal mechanism to modulate t-cell response besides the above car has a variety forms of construction linking two different antibody end-to-end together forms a tandem car expressing two kinds of antibody on the same T cell surface simultaneously forms of this specific car another kinds of physiological car use legand receptor which binds to the paired molecule on the surface of tumor cells instead of specific antibody it increases the ability of T cells to recognize tumor associated targets if we use a venom biotin labeled monoclonal antibody instead of normal antibody as the recognition part of the car the universal car could be formed which has the ability to recognize almost every target antigen according to the different monoclonal antibody being used Carty technology is considered as one of the most promising weapon to fight against cancer it's significant advantages to strengthen the anti-tumor immune response our remarkable car t-cells target the tumor cell in a plan restricted manner no protein antigens such as glycoprotein can also be recognized it overcomes some of the tumor immune escape issues such as MHC an endogenous antigens expression down-regulation by directly targeting the tumor cell surface antigen although this technique manifests such great potential there are still many problems hindering its clinical application as we all know many tumor markers are more or less expressed on healthy cells this may cause so-called on target of tumor toxicity moreover car t-cells have not successfully achieved self-regulation function so far the over expression of cytokines may also cause cytokine relief syndrome or cytokine storm that causes serious body damage or even life risk Carty is a novel technology and still has a long way to become a mature clinical therapeutic method it is performed very well on the treatment of female logical tumors such as leukemia in some cases but is still not effective enough on solid tumors recognition specificity proliferation and persistence tumor micro-environment and self-regulation control should be considered as the most important problems urgent to be addressed we help more and more researchers could join a ducati immunotherapy research and development and make this technology be used on tumor treatment and clinical as soon as possible created by a labs is a world-renowned service provider for immunotherapy our mission is to liberate customers creativity from cumbersome and repetitive experiment work and to help you burst out more innovative inspirations we have one of the world's largest collections of car products from different generations targeting various biomarkers and we are continuing to innovate the next-generation car technology to achieve even greater results based on advanced technologies and years of researches created by alabs offers high quality custom services covering the entire car T therapy development process to best suit your Technical Program and budget requirements which can greatly assist your research preclinical investigation and clinical stage development thank you for watching our video if you have any questions or need more detailed information about car technology please do not hesitate to contact us by email or visit our website we are more than happy to help you with your car project

Channel: Creative Biolabs

Views: 23,295

Rating: 4.7654724 out of 5

Keywords: immunology, immunotherapy, biotechnology, immunity, cancer therapy, tumor therapy, cell therapy, car-t, chimeric antigen receptor, biomedical

Id: HxYpz-b5a3U

Length: 9min 11sec (551 seconds)

Published: Tue May 02 2017