A biodegradable killer microparticle to selectively deplete antigen-specific T cells in vitro and in vivo

• Published in: Oncotarget 2016-03, Vol.7 (11), p.12176-12190
• Main Authors: Wang, Wei, Fang, Kun, Li, Miao-Chen, Chang, Di, Shahzad, Khawar Ali, Xu, Tao, Zhang, Lei, Gu, Ning, Shen, Chuan-Lai
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal; Epitopes, T-Lymphocyte - administration & dosage; Epitopes, T-Lymphocyte - chemistry; Epitopes, T-Lymphocyte - immunology; Graft Rejection - immunology; Graft Rejection - prevention & control; Graft Survival - immunology; Lactic Acid - administration & dosage; Lactic Acid - chemistry; Lactic Acid - immunology; Lymphocyte Depletion - methods; Major Histocompatibility Complex - immunology; Male; Mice; Mice, Inbred C57BL; Microspheres; Ovalbumin - administration & dosage; Ovalbumin - chemistry; Ovalbumin - immunology; Polyglycolic Acid - administration & dosage; Polyglycolic Acid - chemistry; Research Paper: Immunology; T-Lymphocytes - cytology; T-Lymphocytes - immunology
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.7519

The specific eradication of pathogenic T cells for the treatment of allograft rejections and autoimmune disorders without impairment of overall immune function is a fundamental goal. Here, cell-sized poly(lactic-co-glycolic acid) microparticles (PLGA MPs) were prepared as a scaffold to co-display the peptide/major histocompatibility complex (pMHC, target antigen) and anti-Fas monoclonal antibody (apoptosis-inducing molecule) for the generation of biodegradable killer MPs. Ovalbumin (OVA) antigen-targeted killer MPs significantly depleted OVA-specific CD8+ T cells in an antigen-specific manner, both in vitro and in OT-1 mice. After intravenous administration, the killer MPs predominantly accumulated in the liver, lungs, and gut of OT-1 mice with a retention time of up to 48 hours. The killing effects exerted by killer MPs persisted for 4 days after two injections. Moreover, the H-2Kb alloantigen-targeted killer MPs were able to eliminate low-frequency alloreactive T cells and prolong alloskin graft survival for 41.5 days in bm1 mice. Our data indicate that PLGA-based killer MPs are capable of specifically depleting pathogenic T cells, which highlights their therapeutic potential for treating allograft rejection and autoimmune disorders.