Journal of Mazandaran University of Medical Sciences
مجله دانشگاه علوم پزشکی مازندران
J Mazandaran Univ Med Sci
Medical Sciences
http://jmums.mazums.ac.ir
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2022
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بررسی اثر anti-CD3/CD28 Dynabeads و allogeneic PBMCs بر میزان تکثیر سلول های T حاوی گیرنده کایمریک علیه MUC1
Effect of Anti-CD3/CD28 Dynabeads and Allogeneic PBMCs on Expansion of Anti-MUC1 Chimeric Receptor T Cells
ايمونولوژي
Immunology
پژوهشي-کامل
Research(Original)
<span style="font-size:12pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:95%"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:"Times New Roman","serif""><span lang="FA" style="line-height:95%"><span style="font-family:"B Koodak""><span style="color:black"><span style="letter-spacing:-.1pt">سابقه</span></span></span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Koodak""><span style="color:black"><span style="letter-spacing:-.1pt"> و هدف:</span></span></span></span> <span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">در سال</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">های اخیر ایمونوتراپی با استفاده از سلول</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">های </span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:95%">T</span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar""> مهندسی شده دارای گیرنده کایمریک </span></span><br>
<span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">(</span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:95%">CAR T cells</span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">)، به عنوان درمانی نوین و امیدبخش برای برخی بیماری</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">ها بویژه سرطان مورد توجه قرار گرفته است. فرایند تولید سلول </span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:95%">CAR T</span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar""> یک فرآیند چند مرحله</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">ای، پیچیده، زمانبر و هزینه</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">بر می</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">باشد. یکی از مراحل مهم در تولید سلول </span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:95%">CAR T</span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar""> تکثیر این سلول</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">ها به میزان مناسب برای تزریق می</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">باشد. از این رو هدف مطالعه حاضر بررسی روش</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">های تکثیر سلول</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">های </span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:95%">CAR T</span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar""> انسانی در شرایط برون</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">تنی (</span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:95%">ex vivo</span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">) بود.<span style="color:#0e101a"></span></span></span></span></span></span></span></span></span></span><br>
<span style="font-size:12pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:95%"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:"Times New Roman","serif""><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Koodak""><span style="color:black"><span style="letter-spacing:-.1pt">مواد و روش</span></span></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar""><span style="color:black"><span style="letter-spacing:-.1pt"></span></span></span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Koodak""><span style="color:black"><span style="letter-spacing:-.1pt">ها:</span></span></span></span> <span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">در این مطالعه پس از تهیه سلول</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">های مهندسی شده </span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:95%">CAR T</span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar""> اختصاصی علیه آنتی</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">ژن توموری </span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:95%">MUC1</span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">، این سلول</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">ها با استفاده از </span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:95%">rIL-2</span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">، </span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:95%">anti-CD3/C28 Dynadeads</span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar""> و </span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:95%">allogeneic PBMC</span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar""> (روش تکثیر سریع:</span></span> <span dir="LTR" style="font-size:10.0pt"><span style="line-height:95%">REP</span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">) در مدت 14 روز تکثیر شده و با یکدیگر مقایسه شدند.<span style="color:black"></span></span></span></span></span></span></span></span></span></span><br>
<span style="font-size:12pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:95%"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:"Times New Roman","serif""><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Koodak""><span style="color:black"><span style="letter-spacing:-.2pt">یافته</span></span></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar""><span style="color:black"><span style="letter-spacing:-.2pt"></span></span></span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Koodak""><span style="color:black"><span style="letter-spacing:-.2pt">ها:</span></span></span></span> <span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">نتایج نشان داد استفاده از آنتی</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">بادی</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">های </span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:95%">anti-CD3/CD28</span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar""> در نسبت</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">های موثر 1:1 و 1:3 (بید:سلول) به همراه (</span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:95%">IU</span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">100) </span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:95%">rIL-2</span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar""> منجر به افزایش 27/5 برابری در تعداد سلول</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">ها شد، ولی استفاده از </span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:95%">rIL-2</span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar""> به تنهایی و یا</span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:95%">allogeneic PBMC</span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar""> نهایتا منجر به افزایش (بهترتیب) حدود 4/5 و 9 برابری شدند.<span style="color:black"></span></span></span></span></span></span></span></span></span></span><br>
<span style="font-size:12pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:95%"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:"Times New Roman","serif""><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Koodak""><span style="color:black"><span style="letter-spacing:-.2pt">استنتاج:</span></span></span></span> <span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">استفاده از </span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:95%">anti-CD3/CD28</span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar""> به همراه </span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:95%">rIL-2</span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar""> می</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">تواند هر سه سیگنال مورد نیاز برای فعال</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">سازی و تکثیر سلول</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">های </span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:95%">T</span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar""> را فراهم آورد، که می</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">تواند جایگزین مناسبی برای روش</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">های تکثیر پرهزینه و نیازمند تجیهزات گران سلول</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""></span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar"">های </span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:95%">CAR T</span></span><span lang="FA" style="line-height:95%"><span style="font-family:"B Zar""> برای مطالعات حیوانی و انسانی باشد.</span></span><span lang="AR-SA" style="line-height:95%"><span style="font-family:"B Zar""><span style="color:black"><span style="letter-spacing:-.2pt"></span></span></span></span></span></span></span></span></span></span></span>
<span style="font-size:12pt"><span style="line-height:150%"><span style="font-family:"Times New Roman","serif""><b><span style="font-size:10.0pt"><span style="line-height:150%"><span style="font-family:"Arial","sans-serif""><span style="letter-spacing:-.2pt">Background and purpose:</span></span></span></span></b> <span style="font-size:10.0pt"><span style="line-height:150%">In recent years, immunotherapy using chimeric antigen receptor T cells (CAR T cells) has been considered as a novel and promising treatment for some diseases, especially cancer. The CAR T cell production is a multi-step, complex, time-consuming, and costly process. One of the most important steps in production of CAR T cells is expansion of these cells at appropriate numbers for injection. Therefore, the aim of this study was to investigate the methods of expansion for human CAR T cells in ex vivo.</span></span></span></span></span><br>
<span style="font-size:12pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:150%"><span style="text-autospace:none"><span style="font-family:"Times New Roman","serif""><b><span style="font-size:10.0pt"><span style="line-height:150%"><span style="font-family:"Arial","sans-serif"">Materials and methods:</span></span></span></b><b> </b><span style="font-size:10.0pt"><span style="line-height:150%">In this study, specifically engineered CAR T cells against the MUC1 tumor antigen were prepared. The cells were then treated with rIL-2, anti-CD3/C28 Dynadeads, and allogeneic PBMC (Rapid expansion protocol (REP)) for 14 days.</span></span></span></span></span></span></span></span><br>
<span style="font-size:12pt"><span style="line-height:150%"><span style="font-family:"Times New Roman","serif""><b><span style="font-size:10.0pt"><span style="line-height:150%"><span style="font-family:"Arial","sans-serif"">Results:</span></span></span></b><b> </b><span style="font-size:10.0pt"><span style="line-height:150%">The results showed that using anti-CD3/CD28 antibodies in effective ratios; 1: 1 and 1: 3 (bead: cell) along with (IU100) rIL-2 resulted in a 27.5-fold increase in the number of cells. However, the use of rIL-2 alone or allogeneic PBMC eventually resulted in 4.5-fold increase and 9-fold increase, respectively.</span></span></span></span></span><br>
<span style="font-size:12pt"><span style="line-height:150%"><span style="vertical-align:top"><span style="font-family:"Times New Roman","serif""><b><span style="font-size:10.0pt"><span style="line-height:150%"><span style="font-family:"Arial","sans-serif"">Conclusion:</span></span></span></b><span style="font-size:10.0pt"><span style="line-height:150%"> Anti-CD3/CD28 in combination with rIL-2 can provide all three signals required for T cell activation and proliferation which can be a suitable alternative to costly and expensive cell proliferation techniques for animal or human CAR T cell studies.<i></i></span></span></span></span></span></span><br>
<span style="font-size:12pt"><span style="line-height:135%"><span style="tab-stops:121.45pt"><span style="font-family:"Times New Roman","serif""><b><i><span style="font-size:10.0pt"><span style="line-height:135%"></span></span></i></b></span></span></span></span>
ایمونوتراپی, CAR T cell, تکثیر سلولی, سرطان
immunotherapy, CAR T cell, cell proliferation, cancer
1
12
http://jmums.mazums.ac.ir/browse.php?a_code=A-10-14597-1&slc_lang=fa&sid=1
Alireza
Rajabzadeh
علیرضا
رجب زاده
rajabzadeh-a@kaums.ac.ir