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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| Format: | Article |
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Dove Medical Press
2020-07-01
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| Series: | International Journal of Nanomedicine |
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| Online Access: | https://www.dovepress.com/encapsulated-checkpoint-blocker-before-chemotherapy-the-optimal-sequen-peer-reviewed-article-IJN |
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| 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 |
| collection | DOAJ |
| 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 |
| first_indexed | 2024-12-14T13:46:12Z |
| format | Article |
| id | doaj.art-616033c683e348ebb5acf406b16f9771 |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-12-14T13:46:12Z |
| publishDate | 2020-07-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-616033c683e348ebb5acf406b16f97712022-12-21T22:59:19ZengDove Medical PressInternational Journal of Nanomedicine1178-20132020-07-01Volume 155279528855640Encapsulated Checkpoint Blocker Before Chemotherapy: The Optimal Sequence of Anti-CTLA-4 and Doxil Combination TherapyAlimohammadi RAlibeigi RNikpoor ARChalbatani GMWebster TJJaafari MRJalali SAReza 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, liposomehttps://www.dovepress.com/encapsulated-checkpoint-blocker-before-chemotherapy-the-optimal-sequen-peer-reviewed-article-IJNchemotherapyanti-ctla-4checkpoint blockersimmunotherapyliposome. |
| spellingShingle | 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 International Journal of Nanomedicine chemotherapy anti-ctla-4 checkpoint blockers immunotherapy liposome. |
| title | 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_short | 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 |
| topic | chemotherapy anti-ctla-4 checkpoint blockers immunotherapy liposome. |
| url | https://www.dovepress.com/encapsulated-checkpoint-blocker-before-chemotherapy-the-optimal-sequen-peer-reviewed-article-IJN |
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