SYNTHESIS OF CHIMERIC T CELL RECEPTOR WITH OX40 CO-STIMULATORY RECEPTOR TARGETED AGAINST BREAST CANCER CELLS

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KHALEGHI SEPIDEH; RAHBARIZADEH FATEMEH; AZADMANESH KEYHAN; RASAEE MOHAMMADJAVAD; JAFARI FARNOUSH

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Journal: DANESHVAR MEDICINE Year:2011 | Volume:19 | Issue:95 Page(s): 1-8

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Title

SYNTHESIS OF CHIMERIC T CELL RECEPTOR WITH OX40 CO-STIMULATORY RECEPTOR TARGETED AGAINST BREAST CANCER CELLS

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Keywords

CHIMERIC T CELL RECEPTORQ2

NANOBODYQ2

OX40Q2

T LYMPHOCYTEQ2

Abstract

Background and Objective: Chimeric antigen T cell receptors provide a good approach for adoptive immunotherapy of cancer. In this new kind of CHIMERIC T CELL RECEPTOR, nanobodies are replaced as variable fragment of T cell receptor. Nanobodies (VHH) are the smallest fragments of antibodies that have great homology to human VH and low immunogenic potential. VHH-hing-CD28-CD3, construct was made in our laboratory. Tumor cells rarely provide costimulatory signals and hence CAR receptors that transmit just a CD3, signal can only initiate target cell killing and interferon γ release and fail to induce full activation. Although incorporation of a CD28 component results in IL-2 (Interlukin 2) release and limited proliferation, T cell activation remains incomplete. To optimize CAR signaling, tripartite endodomains were constructed which consist of CD28-OX40-CD3z. During T cell activation, OX40 transmits a potent and prolonged T cell activation signal and it is crucial for maintaining an immunological response.Materials and Methods: We designed overlapping primers that contain 60% of OX40 sequence, then, CD28-Ox40-CD3z region was synthesized by SOE-PCR. Consequently, it was replaced with CD28-CD3z region in VHH-Hing-CD28-CD3z construct. Then, this construct was transfected in Jurkat T cells, so IL-2 secretion and T cells proliferation were increased.Results: CD28-OX40-CD3z tripartite cytoplasmic domain provided a full complement of activation, proliferation, and survival signals for enhanced anti-tumor activity.Conclusion: With IL-2 and semi-quantitative RT PCR, it is concluded that mRNA expression of pCDNA-1-hinge-CAR-OX40 and pCDNA-2- hinge-CAR-OX40 constructs are the same but the function of pCDNA-2- hinge-CAR-OX40 construct is more than the others.

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APA: Copy

KHALEGHI, SEPIDEH, RAHBARIZADEH, FATEMEH, AZADMANESH, KEYHAN, RASAEE, MOHAMMADJAVAD, & JAFARI, FARNOUSH. (2011). SYNTHESIS OF CHIMERIC T CELL RECEPTOR WITH OX40 CO-STIMULATORY RECEPTOR TARGETED AGAINST BREAST CANCER CELLS. DANESHVAR MEDICINE, 19(95), 1-8. SID. https://sid.ir/paper/30628/en

Vancouver: Copy

KHALEGHI SEPIDEH, RAHBARIZADEH FATEMEH, AZADMANESH KEYHAN, RASAEE MOHAMMADJAVAD, JAFARI FARNOUSH. SYNTHESIS OF CHIMERIC T CELL RECEPTOR WITH OX40 CO-STIMULATORY RECEPTOR TARGETED AGAINST BREAST CANCER CELLS. DANESHVAR MEDICINE[Internet]. 2011;19(95):1-8. Available from: https://sid.ir/paper/30628/en

IEEE: Copy

SEPIDEH KHALEGHI, FATEMEH RAHBARIZADEH, KEYHAN AZADMANESH, MOHAMMADJAVAD RASAEE, and FARNOUSH JAFARI, “SYNTHESIS OF CHIMERIC T CELL RECEPTOR WITH OX40 CO-STIMULATORY RECEPTOR TARGETED AGAINST BREAST CANCER CELLS,” DANESHVAR MEDICINE, vol. 19, no. 95, pp. 1–8, 2011, [Online]. Available: https://sid.ir/paper/30628/en

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