Kim Hyemin, Seong Keum-Yong, Lee Jung Ho, Park Wonchan, Yang Seung Yun, Hahn Sei Kwang
PHI Biomed Co., 175 Yeoksam-ro, Gangnam-gu, Seoul 06247, Republic of Korea.
Department of Biomaterials Science, Life and Industry Convergence Institute, Pusan National University, 1268-50 Samnangjin-ro, Miryang, Gyeongnam 50463, Republic of Korea.
ACS Biomater Sci Eng. 2019 Oct 14;5(10):5150-5158. doi: 10.1021/acsbiomaterials.9b00961. Epub 2019 Sep 4.
Antigenic peptide-delivery systems have been extensively investigated to harness the immune system for cancer therapy. Cytotoxic T-cell epitope peptide can induce an antigen-specific CD8 T-cell response, which subsequently inhibits the growth of antigen-bearing tumors. However, there are only a few facile tailored delivery systems of antigenic peptide for effective cancer immunotherapy. Here, we developed a biodegradable microneedle patch delivering a hyaluronate (HA)-antigenic peptide conjugate for prophylactic cancer immunotherapy. Cytotoxic T-cell epitope peptide (SIINFEKL) was conjugated to HA, which was loaded into a biodegradable HA microneedle (MN) patch to efficiently deliver an antigen to the immune system in the skin. HA could act as a transdermal vaccine carrier eliciting strong immune responses by the efficient stimulation of immunocompetent cells. The HA-SIINFEKL conjugates loaded into biodegradable MNs were localized near the MN administration site, exhibiting long-term residence for more than 24 h post-administration. Remarkably, a single transdermal vaccination with the MN patch containing HA-SIINFEKL conjugates resulted in a statistically significant inhibition of tumor growth in B16 melanoma model mice by enhancing antigen-specific cytotoxic T-cell responses.
为利用免疫系统进行癌症治疗，人们对抗原肽递送系统进行了广泛研究。细胞毒性T细胞表位肽可诱导抗原特异性CD8 T细胞应答，进而抑制携带抗原的肿瘤生长。然而，用于有效的癌症免疫治疗的抗原肽简易定制递送系统却为数不多。在此，我们开发了一种可生物降解的微针贴片，用于预防性癌症免疫治疗，该贴片可递送透明质酸（HA）-抗原肽偶联物。将细胞毒性T细胞表位肽（SIINFEKL）与HA偶联，然后将其载入可生物降解的HA微针（MN）贴片中，以有效地将抗原递送至皮肤中的免疫系统。HA可作为经皮疫苗载体，通过有效刺激免疫活性细胞引发强烈的免疫应答。载入可生物降解MNs的HA-SIINFEKL偶联物定位于MN给药部位附近，给药后24小时以上仍能长期留存。值得注意的是，用含有HA-SIINFEKL偶联物的MN贴片进行单次经皮接种，通过增强抗原特异性细胞毒性T细胞应答，在B16黑色素瘤模型小鼠中对肿瘤生长产生了具有统计学意义的抑制作用。
