Encapsulated Checkpoint Blocker Before Chemotherapy: The Optimal Sequence of Anti-CTLA-4 and Doxil Combination Therapy

Reza Alimohammadi,1 Razieh Alibeigi,2 Amin Reza Nikpoor,3 Ghanbar Mahmoodi Chalbatani,4 Thomas J Webster,5 Mahmoud Reza Jaafari,6,7,* Seyed Amir Jalali1,* 1Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Immunology, School of...

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Autores principales:	Alimohammadi R, Alibeigi R, Nikpoor AR, Chalbatani GM, Webster TJ, Jaafari MR, Jalali SA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	chemotherapy anti-ctla-4 checkpoint blockers immunotherapy liposome. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/616033c683e348ebb5acf406b16f9771
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spelling	oai:doaj.org-article:616033c683e348ebb5acf406b16f97712021-12-02T05:22:56ZEncapsulated Checkpoint Blocker Before Chemotherapy: The Optimal Sequence of Anti-CTLA-4 and Doxil Combination Therapy1178-2013https://doaj.org/article/616033c683e348ebb5acf406b16f97712020-07-01T00:00:00Zhttps://www.dovepress.com/encapsulated-checkpoint-blocker-before-chemotherapy-the-optimal-sequen-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Reza Alimohammadi,1 Razieh Alibeigi,2 Amin Reza Nikpoor,3 Ghanbar Mahmoodi Chalbatani,4 Thomas J Webster,5 Mahmoud Reza Jaafari,6,7,* Seyed Amir Jalali1,* 1Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Immunology, School of Medicine, Mashhad University of Medical Sciences, Tehran, Iran; 3Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran; 4Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; 5Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA; 6Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; 7Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran*These authors contributed equally to this workCorrespondence: Seyed Amir JalaliDepartment of Immunology, Medical School, Shahid Beheshti University of Medical Sciences, Tehran 198571-7443, IranTel +98 21-238 725 45Fax + 98 21-224 399 70Email jalalia@sbmu.ac.irMahmoud Reza JaafariBiotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 91775-1365, IranTel +98 51-38823255Fax +98 51-38823251Email Jafarimr@mums.ac.irIntroduction: Today, a new paradigm has emerged for cancer treatment introducing combination therapies. Doxil, a liposomal doxorubicin serving as a chemotherapeutic agent, is an effective immunogenic killer of cancer cells. Anti-CTLA-4 has been approved for the treatment of some cancers, including melanoma, but side effects have limited its therapeutic potential.Methods: In this study, two approaches were utilized to increase treatment efficiency and decrease the side effects of anti-CTLA-4, combining it with chemotherapy and encapsulation in a PEGylated liposome. A different sequence of anti-CTLA-4 and Doxil was assessed in combination therapy using non-liposomal and liposomal anti-CTLA-4.Results: Our results showed that liposomal anti-CTLA-4 reduced the size of established tumors and increased survival in comparison with non-liposomal anti-CTLA-4 in a well-established B16 mouse melanoma model. In combination therapy with Doxil, only the administration of anti-CTLA-4 before Doxil showed synergism in both non-liposomal and liposomal form and increased the CD8+/regulatory T cell ratio.Discussion: In summary, our results demonstrate the potential of utilizing a nanocarrier system for the delivery of checkpoint blockers, such as anti-CTLA-4 which further showed potential in a combination therapy, especially when administered before chemotherapy.Keywords: chemotherapy, anti-CTLA-4, checkpoint blockers, immunotherapy, liposomeAlimohammadi RAlibeigi RNikpoor ARChalbatani GMWebster TJJaafari MRJalali SADove Medical Pressarticlechemotherapyanti-ctla-4checkpoint blockersimmunotherapyliposome.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 5279-5288 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	chemotherapy anti-ctla-4 checkpoint blockers immunotherapy liposome. Medicine (General) R5-920
spellingShingle	chemotherapy anti-ctla-4 checkpoint blockers immunotherapy liposome. Medicine (General) R5-920 Alimohammadi R Alibeigi R Nikpoor AR Chalbatani GM Webster TJ Jaafari MR Jalali SA Encapsulated Checkpoint Blocker Before Chemotherapy: The Optimal Sequence of Anti-CTLA-4 and Doxil Combination Therapy
description	Reza Alimohammadi,1 Razieh Alibeigi,2 Amin Reza Nikpoor,3 Ghanbar Mahmoodi Chalbatani,4 Thomas J Webster,5 Mahmoud Reza Jaafari,6,7,* Seyed Amir Jalali1,* 1Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Immunology, School of Medicine, Mashhad University of Medical Sciences, Tehran, Iran; 3Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran; 4Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; 5Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA; 6Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; 7Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran*These authors contributed equally to this workCorrespondence: Seyed Amir JalaliDepartment of Immunology, Medical School, Shahid Beheshti University of Medical Sciences, Tehran 198571-7443, IranTel +98 21-238 725 45Fax + 98 21-224 399 70Email jalalia@sbmu.ac.irMahmoud Reza JaafariBiotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 91775-1365, IranTel +98 51-38823255Fax +98 51-38823251Email Jafarimr@mums.ac.irIntroduction: Today, a new paradigm has emerged for cancer treatment introducing combination therapies. Doxil, a liposomal doxorubicin serving as a chemotherapeutic agent, is an effective immunogenic killer of cancer cells. Anti-CTLA-4 has been approved for the treatment of some cancers, including melanoma, but side effects have limited its therapeutic potential.Methods: In this study, two approaches were utilized to increase treatment efficiency and decrease the side effects of anti-CTLA-4, combining it with chemotherapy and encapsulation in a PEGylated liposome. A different sequence of anti-CTLA-4 and Doxil was assessed in combination therapy using non-liposomal and liposomal anti-CTLA-4.Results: Our results showed that liposomal anti-CTLA-4 reduced the size of established tumors and increased survival in comparison with non-liposomal anti-CTLA-4 in a well-established B16 mouse melanoma model. In combination therapy with Doxil, only the administration of anti-CTLA-4 before Doxil showed synergism in both non-liposomal and liposomal form and increased the CD8+/regulatory T cell ratio.Discussion: In summary, our results demonstrate the potential of utilizing a nanocarrier system for the delivery of checkpoint blockers, such as anti-CTLA-4 which further showed potential in a combination therapy, especially when administered before chemotherapy.Keywords: chemotherapy, anti-CTLA-4, checkpoint blockers, immunotherapy, liposome
format	article
author	Alimohammadi R Alibeigi R Nikpoor AR Chalbatani GM Webster TJ Jaafari MR Jalali SA
author_facet	Alimohammadi R Alibeigi R Nikpoor AR Chalbatani GM Webster TJ Jaafari MR Jalali SA
author_sort	Alimohammadi R
title	Encapsulated Checkpoint Blocker Before Chemotherapy: The Optimal Sequence of Anti-CTLA-4 and Doxil Combination Therapy
title_short	Encapsulated Checkpoint Blocker Before Chemotherapy: The Optimal Sequence of Anti-CTLA-4 and Doxil Combination Therapy
title_full	Encapsulated Checkpoint Blocker Before Chemotherapy: The Optimal Sequence of Anti-CTLA-4 and Doxil Combination Therapy
title_fullStr	Encapsulated Checkpoint Blocker Before Chemotherapy: The Optimal Sequence of Anti-CTLA-4 and Doxil Combination Therapy
title_full_unstemmed	Encapsulated Checkpoint Blocker Before Chemotherapy: The Optimal Sequence of Anti-CTLA-4 and Doxil Combination Therapy
title_sort	encapsulated checkpoint blocker before chemotherapy: the optimal sequence of anti-ctla-4 and doxil combination therapy
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/616033c683e348ebb5acf406b16f9771
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Encapsulated Checkpoint Blocker Before Chemotherapy: The Optimal Sequence of Anti-CTLA-4 and Doxil Combination Therapy

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