Production of novel protein therapeutics to improve targeted cancer therapy Al-Qahtani, Alanod
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Publication date: 2019
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Al-Qahtani, A. (2019). Production of novel protein therapeutics to improve targeted cancer therapy. University of Groningen.
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Chapter 9:
ﻪ�ﻠبﻘﺘﺴﻤﻟا ﻪ�ؤﺮﻟاو ﺺﺨﻠﻤﻟا
225 ﻟاو ﺺﺨﻠﻤﻟا ﮫﯿﻠﺒﻘﺘﺴﻤﻟا ﮫﯾؤﺮ : ﻞﺧﺪﺘﻟا ﻰﻠﻋ ةرﺪﻘﻟا ﻊﻣ نﺎطﺮﺴﻠﻟ ةدﺎﻀﻤﻟا تﺎﺟﻼﻌﻟا ﻦﻣ ﺪﯾﺪﻌﻟا رﻮﺤﻣ ﺎﯿﻟﺎﺣ ﻲھ ﺔﻓﺪﮭﺘﺴﻤﻟا ﺔﯿﻧﺎطﺮﺴﻟا تﺎﺟﻼﻌﻟا ﻰﻠﻋ ءﺎﻘﺒﻟا وأ ﺔﯿﻧﺎطﺮﺴﻟا ﺎﯾﻼﺨﻟا ﻮﻤﻧ ﻲﻓ ﺔﻓﺪﮭﺘﺴﻤﻟا ﺔﯿﻧﺎطﺮﺴﻟا تﺎﺟﻼﻌﻟا ﻦﻣ ﺪﯾﺪﻌﻟا ﻰﻠﻋ ﺔﻘﻓاﻮﻤﻟا ﺖﻤﺗ .ةﺎﯿﺤﻟا ﺪﯿﻗ ) ءاوﺪﻟاو ءاﺬﻐﻟا ةرادإ ﻞﺒﻗ ﻦﻣ FDA برﺎﺠﺘﻟا ﻲﻓ ﺮﺧﻵا ﺾﻌﺒﻟا ﺔﺳارد ﻢﺘﺗ .نﺎطﺮﺴﻟا ﻦﻣ ﺔﻨﯿﻌﻣ عاﻮﻧأ جﻼﻌﻟ ( ﯿﻧﺎطﺮﺴﻟا ﺎﯾﻼﺨﻟا ﻰﻠﻋ ﺔﻓﺪﮭﺘﺴﻤﻟا تﺎﺟﻼﻌﻟا .ﺔﯾﺮﯾﺮﺴﻟا ﻞﺒﻗ تارﺎﺒﺘﺧﻻا ﻲﻓ ﺎﮭﻨﻣ ﺪﯾﺪﻌﻟاو ، ﺔﯾﺮﯾﺮﺴﻟا ﺔ نﻮﻜﯾ ﺪﻗ دﻮﺟو مﺪﻋ وأ ، ﺔﯾودﻸﻟ ﺔﻣوﺎﻘﻣ ﻰﻠﻋ يﻮﻄﻨﺗ ﺎﻤﺑرو ، دﻮﯿﻗ ﺎﮭﻟ بﻮﻠﻄﻤﻟا ﺺﯿﺼﺨﺘﻟا ﻰﻠﻋ هﺎﻧدأ ﻞﺼﻓ ﻞﻛ ﺰﻛﺮﯾ . .ﮫﯿﻓ ﻲﻀﻤﻟا ﻦﻜﻤﯾ يﺬﻟا ﻲﻠﺒﻘﺘﺴﻤﻟا ﻞﻤﻌﻟا رﺎﮭظإو ﺎﮭﻠﺤﻟ ﻼﺋاﺪﺒﻟا ﺮﯿﻓﻮﺗو دﻮﯿﻘﻟا ﻲﻓ ﻲﻧﺎﺜﻟا ﻞﺼﻔﻟا ط ﺔﯿﺟﻼﻌﻟا ﺔﯾودﻷا جﺎﺘﻧﻹ ﺔﻔﻠﺘﺨﻣ تﺎﯿﺠﯿﺗاﺮﺘﺳﻻ ﺔﻌﺟاﺮﻣ ﺎﻨﯾﺮﺟأ ، ﻲﻓ لﻮﻌﻔﻤﻟا ﺔﻠﯾﻮ نﺎطﺮﺴﻟا لا ﺪﻌﯾو .تارﺪﺨﻤﻟا ﻢﯿﻠﺴﺘﻟ ﺎھﺪﺋاﻮﻓو ، PEGylation لﺎﺑ دﺎﺤﺗﻻا و Albumin يوذ ﻞﺜﻤﺗو ﺎﺻﺎﺧ اﺰﯿﻛﺮﺗ نﺎطﺮﺴﻟا جﻼﻋ ﻲﻓ ﺎﮭﻣاﺪﺨﺘﺳاو ﺔﯿﺟﻼﻌﻟا تﺎﻨﯿﺗوﺮﺒﻟا ﻲﻓ ﻦﯿﻠﻜﺸﻟا ماﺪﺨﺘﺳا نإ .ﺎﯿﻤﻠﻋ ﮫﺸﻗﺎﻨﻣو ﺎﻣاﺪﺨﺘﺳا ﺮﺜﻛﻷا ﺔﯿﺟﻼﻌﻟا ﻞﻣاﻮﻌﻟا نأ ﺖﺒﺛ ﺪﻗو .ﺔﯿﺟﻼﻌﻟا تﺎﻨﯿﺗوﺮﺒﻟا ﻞﺒﻘﺘﺴﻣ ﺎﻤھو ﺔﯾﻮﯿﺣ ﺔﯿﻤھأ ﺎﻤﮭﻟ ءاوﺪﻟا ﻞﯿﺻﻮﺗ ﻦﯿﺴﺤﺗو و ﻞﺼﻤﻟا ﺮﻤﻋ ﻒﺼﻧ ةﺮﺘﻓ ﻦﻣ تداز ﺪﻗ ﺔﻟﺪﻌﻤﻟا ظﺎﻔﺤﻟا ﻊﻣ ءاوﺪﻟا ﻞﯿﺻﻮﺗ ﻰﻠﻋ ةرﺪﻘﻟا ﻦﯿﺴﺤﺗو ، نﺎﺑوﺬﻟا ﺔﯿﻠﺑﺎﻗ ﻲﻤﺤﺗ ﺔﻘﯾﺮﻄﺑو فﺪﮭﺘﺴﻤﻟا نﺎطﺮﺴﻟا جﻼﻋ ﻲﻓ ﻚﻟﺬﻛو ﻲﻋﺎﻨﻤﻟا جﻼﻌﻟا ﻲﻓ راودأ ﺎﻨﺘﺳارد حﺮﺘﻘﺗ .ﺎﮭطﺎﺸﻧ ﻰﻠﻋ .ﻲﻋﺎﻨﻤﻟا زﺎﮭﺠﻟا ﻦﻣ ﻢﯾﺰﻧإ / ﻦﯿﺗوﺮﺒﻟا ﻲﻓ ﺚﻟﺎﺜﻟا ﻞﺼﻔﻟا ﻞﻟ ﺪﯾﺪﺟﺮﯿﻐﺘﻣ لﺰﻋ ﻲﻓ ﺎﻨﺤﺠﻧ ﻒﯿﻛ ﺶﻗﺎﻨﻧ ، CPG2 ﻏﺮﻟا ﻰﻠﻋ . ﻦﯿﺑ ﻖﯿﺛﻮﻟا ﮫﺑﺎﺸﺘﻟا ﻦﻣ ﻢ ﻦﻣ هدﺎﻀﻤﻟا ﻢﺴﺟﻷا ﻞﻋﺎﻔﺘﯾ ﻢﻟ ، يﺪﯿﻠﻘﺘﻟاو ﺪﯾﺪﺠﻟا ﻢﯾﺰﻧﻹا CPG2 لا ﻊﻣ ﺪﯾﺪﺠﻟا CPG2 ﻦﻣ Pseudomonas sp ﺔﻟﻼﺳ . RS-16 تﺎﻤﯾﺰﻧﻻا نأ ﻰﻠﻋ لﺪﯾ اﺬھ .يﺮﯾﺮﺴﻟا ماﺪﺨﺘﺳﻻا ﻲﻓ ﺎﯿﻟﺎﺣ ﻲھ ﻲﺘﻟا لوﺎﻨﺗ نأ ﻲﻓ ﺎﯾاﺰﻣ ةﺰﯿﻤﻟا هﺬﮭﻟ نﻮﻜﯾ ﺪﻗ .فﺮﺼﺘﻟﺎﺑ ﻦﯿﻠﻘﺘﺴﻣ ﻦﯿﻨﺛﻻا لﻮﻛﻮﺗوﺮﺑ ﻲﻓ ﻲﻟاﻮﺘﻟا ﻰﻠﻋ ﻦﯿﺋاود ADEPT ﻊﻣ ﺔﯿﻟﺎﺤﻟا ﺔﺠﻟﺎﻌﻤﻠﻟ ةرﺮﻜﺘﻤﻟا تﺎﻋﺮﺠﻟا ﻖﯿﻌﺗ ﻲﺘﻟا ةدﺎﻀﻤﻟا مﺎﺴﺟﻷا تﺎﺑﺎﺠﺘﺳا ﻦﻣ ﻞﻠﻘﯾ نأ ﻦﻜﻤﯾ Ps CPG2 لا ﺮﻓﻮﺗ نإ . CPG2 جﻼﻋ ﻲﻓ ﺔﯿﺟﻼﻌﻟا ﮫﺗﺪﺋﺎﻓ ﻦﯿﺴﺤﺗ ﻲﻓ ةﺮﯿﺒﻛ ﺔﯿﻤھأ وذ نﻮﻜﯾ نأ ﻦﻜﻤﯾ ﺪﯾﺪﺠﻟا
ﺘﻟا ﺔﻋﺮﺠﻟا تﺎﺳارﺪﻟ ﺔﺻﺮﻓ ﺮﻓﻮﯿﺳو نﺎطﺮﺴﻟا جﻼﻌﻟ ﺖﯿﺴﻜﯾﺮﺗﻮﺜﯿﻤﻟا تﺎﻋﺮﺟ ﺪﯿﻌﺼﺗ ﻰﻟإ ﺎھروﺪﺑ يدﺆﺗ ﺪﻗ ﻲ ﻦﯾﺬﻟا ﻰﺿﺮﻤﻟا ﻦﻣ ةدﺎﻀﻤﻟا مﺎﺴﺟﻷا ﻞﻋﺎﻔﺗ ىﺪﻣ ﻲﻓ ﺚﺤﺒﺗ نأ ﺔﯿﻠﺒﻘﺘﺴﻤﻟا تﺎﺳارﺪﻟا ﻰﻠﻋ ﺐﺠﯾ .ﺔﯿﻟﺎﻌﻓ ﺮﺜﻛأ ـﻟﺎﺑ اﻮﺠﻟﻮﻋ PSG2 ـﻟ ﺪﯾﺪﺠﻟا ﻞﻜﺸﻟا ﻊﻣ ﻞﻋﺎﻔﺘﺗ ﻻ وأ ﺔﻔﻠﺘﺨﻣ ﺔﻘﯾﺮﻄﺑ CPG2 ﺎﯾاﺰﻣ ﻚﻠﺘﻤﺗ ﻲﻟﺎﺘﻟﺎﺑو ، ﮫﯿﻜﯿﻨﯿﻠﻜﻟا . ﻲﻓ ﻔﻟا ﻊﺑاﺮﻟا ﻞﺼ يوﻮﻨﻟا ﺾﻤﺤﻟا ﻂﻠﺧ ﻖﯾﺮط ﻦﻋ ﺎﻨﻤﻗ ﻒﯿﻛ ﺎﻨﺸﻗﺎﻧ ، DNA ـﻟ ةﺪﯾﺪﺟ تاﺮﯿﻐﺘﻣ ءﺎﺸﻧﺈﺑ CPG2 ﻦﻣ ﺮﺜﻛأ ﺎًطﺎﺸﻧ ﺖﺠﺘﻧأ تاﺮﻔط ﻊﻣ 110 -200 ٪ لا ﻦﻣ CPG2 ﻰﻟإ ﺎﻧﺪﻟا تﻼﺴﻠﺴﺗ ﻞﯿﻠﺤﺗ ﺮﯿﺸﯾ .مﺪﺨﺘﺴﻤﻟا ﻲﻨﯿﻣﻷا ﺾﻤﺤﻟا لاﺪﺒﺘﺳا ﺐﺒﺴﯾ ﺮﯿﻐﺘﻣ ﻞﻛ ﻲﻓ ﺔﻄﻘﻨﻟا ﺔﯾدﺎﺣأ ةﺮﻔط ثوﺪﺣ I100T و T239A و G123S . لا ﺔﺳارد تﺮﮭظأ CD ـﻟا ﻦﻣ CPG2 اﺬھ ﺮﯿﺸﯾو .مﺪﺨﺘﺴﻤﻟا عﻮﻨﻟا ﻦﻣ ﻰﻠﻋأ ﺎﻔﻟأ ﺐﻟﻮﻠﻟا ىﻮﺘﺤﻣ نأ ﻂﻠﺘﺨﻤﻟا ﻲﻓ ﻞﻤﺘﺤﻤﻟا ماﺪﺨﺘﺳﻼﻟ ﺪﯾﺪﺠﻟا ﻒﻠﺗﺆﻤﻟا زاﺪﯿﺑرﺎﻛﻮﻠﻐﻟ يدﺎﺼﺘﻗﻻا جﺎﺘﻧﻺﻟ سﺎﺳأ ﻰﻟإ ﻞﻤﻌﻟا ADEPT وأ / و لا ﻖﯿﺒﻄﺗ ﻊﯿﺳﻮﺗ ﻦﻜﻤﯾ .تارﺪﺨﻤﻟا ﻦﻣ مﻮﻤﺴﻟا ﺔﻟازإ CPG2 ﮫﯿﻜﯿﻨﯿﻠﻛا تﺎﻘﯿﺒﻄﺗ ﻞﻤﺸﯿﻟ ﺎًﺜﯾﺪﺣ ﮫﻨﯾﻮﻜﺗ ﻢﺗ يﺬﻟا ﻲﻓ ﮫﻟﺰﻋ ﻢﺗ يﺬﻟا ﻰﻠﻋﻷا طﺎﺸﻨﻟا وذ ﺪﯾﺪﺠﻟا ﺰﯾﺪﯿﺑرﺎﻛﻮﻠﺠﻠﻟ ﻦﻜﻤﯾ .نﺎطﺮﺴﻟا ﺮﯿﻏ ىﺮﺧأ ﺚﻟﺎﺜﻟا ﻞﺼﻔﻟا أ نﻮﻜﯾ ن ﻮھ ﺎﻤﻛ) ﺔﻟﺪﻌﻤﻟا ﺮﯿﻗﺎﻘﻌﻟا ﻖﯿﺒﻄﺗ ﻦﻜﻤﯾ .ﺖﯿﺴﻜﯾﺮﺗﻮﺜﯿﻤﻟا ﻦﻣ ةﺪﺋاز ﺔﻋﺮﺟ تﻻﺎﺣ ﻲﻓ مﻮﻤﺴﻟا ﺔﻟازإ ﻲﻓ ﺔﻤﯿﻗ اذ ﻲﻓ هﺎﻧدأ ﺢﺿﻮﻣ ﻞﺼﻔﻟا ﺲﻣﺎﺨﻟا .ﻰﻠﻋأ طﺎﺸﻧ ﻊﻣ ﮫﯿﻠﻋﺎﻔﻟا ﻞﯾﻮط ءاود جﺎﺘﻧﻹ ةﺪﯾﺪﺠﻟا ﺔﻄﻠﺘﺨﻤﻟا تاﺮﯿﻐﺘﻤﻟا ﻲﻠﻋ ( ﻲﻓ ﻞﺼﻔﻟا ﺲﻣﺎﺨﻟا جﺎﺘﻧإ ﻮھ فﺪﮭﻟا نﺎﻛ ، CPG2 ﻟا ﻞﯾﻮط ﮫﯿﻠﻋﺎﻔ ﻦﻣ ﻦﯿﻠﻜﺷ ﺎﻧﺄﺸﻧﺈﺑ ﺎﻤﺤﺠﻧ . CPG2 : CPG2 لا ﻊﻣ ﺎﯾدﺎﺣأ ﻂﺒﺗﺮﻣ PEG و ، CPG2 ﻊﻣ ﺪﺤﺘﻣ HSA ﻟاو ﺔﯿﺋﺎﯿﻤﯿﻛﻮﯿﺒﻟا تﻼﯿﻠﺤﺘﻟا ترﺎﺷأ . يﻮﯿﺤﻟا طﺎﺸﻨ اوﺮﮭظأ ﺎﻤﻛ .زاﺪﯿﺑرﺎﻛﻮﻠﺠﻠﻟ ﺔﯿﻔﯿظﻮﻟا ﺔﻄﺸﻧﻷا ﻰﻠﻋ ظﺎﻔﺤﻟا ﻢﺗو ، ﻦّﺴﺤﻣ ﻒﺼﻧ ﺮﻤﻋ ﮫﻟ نﺎﻛ ﻞﻜﺷ ﻞﻛ نأ ﻰﻟإ لا ﻦﻣ نﺎﺴﻧﻹا ﺰﯿﺗوﺮﺒﻟ ﺔﻣوﺎﻘﻣ ﺮﺜﻛأ اﻮﻧﺎﻛو يﺮﺸﺒﻟا مﺪﻟا ﻞﺼﻣ ﻲﻓ ﺎًﯿﻟﺎﻋ ﺎًﺗﺎﺒﺛ CPG2 ﻰﻠﻋ .مﺪﺨﺘﺴﻤﻟا ﻲﻠﺻﻷا ا يﻮﺘﺴﻣ ﻲﻠﻋ ﺎﮭﻋﻮﻧ ﻦﻣ لوأ ﻲھ ﺔﺳارﺪﻟا هﺬھ ، ﺎﻨﻤﻠﻋ ﺪﺣ ل CPG2 ﻦﻣ ﺔﻣاﺪﺘﺳا ﻞﻗأو ﺮﻘﺘﺴﻣ ﮫﻧﺄﺑ ﺖﺒﺛاو لا ﻦﯿﻠﻜﺸﻟا PEGylated ﻟاو ﺤﺘﻤ لﺎﺑ ﺪ HSA ﺮﺒﻛأ ﺔﯿﻟﺎﻌﻓ ﺎﮭﻟ نﻮﻜﯾ ﺪﻗ نأ ﺎﮭﯿﻟإ ﺎﻨﻠﺻﻮﺗ ﻲﺘﻟا ﺞﺋﺎﺘﻨﻟا ﺮﯿﺸﺗو . و ﺮﯿﻗﺎﻘﻌﻟا ﻦﻣ مﻮﻤﺴﻟا ﺔﻟازإ ﻲﻓ ADEPT ، جﻼﻌﻟا ةرود ﺔﻟﺎطﻹ ﻲﻟاﻮﺘﻟا ﻰﻠﻋ ﺾﯾﺮﻤﻠﻟ ﻦﯿﻠﻜﺸﻟا ءﺎﻄﻋإ ﻦﻜﻤﯾ .
227 ﻦﻣ ﺔﻟﺪﻌﻤﻟا ةﺪﯾﺪﺠﻟا لﺎﻜﺷأﻻا هﺬھ ماﺪﺨﺘﺳﺎﺑ ﺔﯾﺮﯾﺮﺴﻟا CPG2 نإ .ﺮﯿﻗﺎﻘﻌﻟا ﻦﻣ مﻮﻤﺴﻟا ﺔﻟازإو نﺎطﺮﺴﻟا جﻼﻌﻟ ﻰﻟإ ﺔﻔﻠﺘﺨﻣ تﻻِﺪَﻌُﻣ جﺎﺘﻧإ CPG2 لا ﻦﻣ ةﺪﯾﺪﺟ لﺎﻜﺷأ جﺎﺘﻧﺈﺑ ةﺪﯾﺪﺠﻟا ﮫﺗاﺮﯿﻐﺘﻣو CPG2 ﻤﻟ تارود ﻦﻣ ﺪﯾﺰ ءاﺮﺟﺈﺑ ﺢﻤﺴﯾو ، ﮫﯿﻜﯿﻨﯿﻠﻜﻟا تﺎﺳارﺪﻠﻟ ًﺎﻤﺳﺎﺣ ًاﺮﺴﺟ تﺎﻧاﻮﯿﺤﻟا رﺎﺒﺘﺧا نﻮﻜﯿﺳ .ﺎﯿﻋﻮﺒﺳا ﻞﻗا تﺎﯿﻤﻜﺑ ﮫﯿﺟﻼﻌﻟا ـﻠﻟ ﺔﻔﻠﺘﺨﻤﻟا لﺎﻜﺷﻷا ﺮﻤﻋ ﻒﺼﻨﻟ ﻲﻟوأ ﻢﯿﯿﻘﺗ CPG2 .ﺎھراﺮﻘﺘﺳاو ﺎﮭﺘﺑﺎﺠﺘﺳاو ، ﻲﺤﻟا ﻢﺴﺠﻟا ﻲﻓ ﻲﻓ سدﺎﺴﻟا ﻞﺼﻔﻟا ،نﺎطﺮﺴﻟا جﻼﻌﻟ ﺔﻔﻠﺘﺨﻣ تﺎﺌﯾﺰﺟ ﺎﻨﻣﺪﺨﺘﺳا ، superantigens ﺪﯾﺪﺤﺗ ﻮھ فﺪﮭﻟا . ﻞﻟ ﺔﯿﺒﻧﺎﺠﻟا رﺎﺛﻵا ﺪﺣأ هرﺎﺒﺘﻋﺎﺑ مﺪﻟا ﻂﻐﺿ ضﺎﻔﺨﻧا ﺐﺒﺴﺗ ﻲﺘﻟا تﺎﺌﯾﺰﺠﻟا هﺬھ ﻰﻠﻋ (ﻖطﺎﻨﻤﻟا) ﺔﻘﻄﻨﻤﻟا superantigen جﺎﺘﻧإ ﻰﻟإ ﻚﻟذ يدﺆﯿﺳو . superantigen ﻞﻗأ ﻊﻣ ﻖطﺎﻨﻤﻟا هﺬھ ﺔﻟازإ ﻖﯾﺮط ﻦﻋ ﺔﻟﺪﻌﻤﻟا ـﻟا ﮫﻨﺴﺤﻣ ﻖطﺎﻨﻣ ﺔﻌﺑرأ ﻦﻣ ﺮﺜﻛأ ﺎﻨﻟﺰﻋ ﺪﻘﻟ .ﺔﯿﺒﻧﺎﺠﻟا رﺎﺛﻵا codon لا ﻲﻠﻋ SEA و SEB و TSST-1 و SPEA ﻞﻗﻷا ﻰﻠﻋ ﺎﻣ ﺪﺣ ﻰﻟإ ﺔﯿﺋﺎﺘﻟا ﺎﯾﻼﺨﻟا ﻂﯿﺸﻨﺗ ﻰﻠﻋ ةرﺪﻘﻟا ﻢﮭﯾﺪﻟ ﮫﻌﺑرﻻا ءﻻﺆھ . 66 ٪ لا ﻦﻣ SEB ىﺪﻟ نﺎﻛ .ﺔﺣﺎﺘﻤﻟا superantigens ﺔﯿﻧﺎطﺮﺴﻟا ﺎﯾﻼﺨﻟا ﻞﺘﻗ ﻰﻠﻋ ةرﺪﻘﻟا DLD1 ﻊﻣ ﮫﺟﺰﻣ ﺪﻨﻋ PBMCs ﻦﻣ ﻦﯿﻨﺛا ماﺪﺨﺘﺳﺎﺑ ، ﺎﻧﺮﮭظأ .تﺎﻨﯿﻛﻮﺘﯿﺴﻟا جﺎﺘﻧإ ﻰﻟإ يدﺆﺗو ﺔﯿﺋﺎﺘﻟا ﺎﯾﻼﺨﻟا ﻂﺸﻨﺗ ﻲﺘﻟا superantigens ، SEA و SPEA نﻮﻜﯾ نأ ﻦﻜﻤﯾ اﺬھو ، مﺪﻟا ﻂﻐﺿ ضﺎﻔﺨﻧا ﻰﻟإ يدﺆﺗ نأ ﻦﻜﻤﯾ ﻲﺘﻟا ﺔﯿﻋوﻷا ﻊﺳﻮﺗ ﺐﺒﺴﺗ ﺎﮭﻧأ ﻵا ﺪﺣأ ﻦﻣ ﻞﺧاﺪﺘﻣ ﺪﯿﺘﺒﺑ ﺮﺸﻋ ﺔﻌﺴﺗ ﻒﯿﻟﻮﺗو ﻢﯿﻤﺼﺘﺑ ﺎﻨﻤﻗ ﻢﺛ .ﺎﮭﯿﻓ بﻮﻏﺮﻤﻟا ﺮﯿﻏ ﺔﯿﺒﻧﺎﺠﻟا رﺎﺛ SPEA ﺎﻨﻨﻜﻤﺗو ، ﺎھﺪﯾﺪﺤﺗ ﻢﺗ ﻲﺘﻟا ﺔﯿﻨﯿﻣﻷا ضﺎﻤﺣﻷا ﺔﻟازإ .ﺚﺤﺘﺴﻤﻟا مﺪﻟا ﻂﻐﺿ ضﺎﻔﺨﻧا ﻲﻓ ﻢھﺎﺴﺗ ﻲﺘﻟا تاﺪﯿﺘﺒﺒﻟا ﺪﯾﺪﺤﺗ ﻦﻣ ﻟا تﺎﻧﺎﻜﻣﻹا تاذ ﺎﯾﻼﺨﻟا ﻦﻣ ﺔﻔﻠﺘﺨﻣ عاﻮﻧأ جﺎﺘﻧﻹ ﻖﯾﺮﻄﻟا ﺪﮭﻤﺗ نأ ﺐﺠﯾ ﺔﯿﻋوﻷا ﻊﺳﻮﺘﻟ ﻲﺒﻧﺎﺠﻟا ﺮﺛﻸﻟ ﺔﻀﻔﺨﻨﻤ .
