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



Alimohammadi R1 ; Alibeigi R2 ; Nikpoor AR3 ; Chalbatani GM4 ; Jwebster T5 ; Jaafari MR6, 7 ; Jalali SA1
Authors
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Authors Affiliations
  1. 1. Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  2. 2. Department of Immunology, School of Medicine, Mashhad University of Medical Sciences, Tehran, Iran
  3. 3. Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
  4. 4. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Chemical Engineering, Northeastern University, Boston, 02115, MA, United States
  6. 6. Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
  7. 7. Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Source: International Journal of Nanomedicine Published:2020


Abstract

Introduction: 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. © 2020 Alimohammadi et al.
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