经皮给药的乳腺癌疫苗的评估。

Evaluation of a Particulate Breast Cancer Vaccine Delivered via Skin.

机构信息

Department of Pharmaceutical Science, Wegmans School of Pharmacy, St. John Fisher College, 3690 East Ave., Rochester, New York, 14618, USA.

Research and Development, Nexus Pharmaceuticals, Vernon Hills, Illinois, 60061, USA.

出版信息

AAPS J. 2019 Jan 2;21(2):12. doi: 10.1208/s12248-018-0285-7.

Abstract

Breast cancer impacts female population globally and is the second most common cancer for females. With various limitations and adverse effects of current therapies, several immunotherapies are being explored. Development of an effective breast cancer vaccine can be a groundbreaking immunotherapeutic approach. Such approaches are being evaluated by several clinical trials currently. On similar lines, our research study aims to evaluate a particulate breast cancer vaccine delivered via skin. This particulate breast cancer vaccine was prepared by spray drying technique and utilized murine breast cancer whole cell lysate as a source of tumor-associated antigens. The average size of the particulate vaccine was 1.5 μm, which resembled the pathogenic species, thereby assisting in phagocytosis and antigen presentation leading to further activation of the immune response. The particulate vaccine was delivered via skin using commercially available metal microneedles. Methylene blue staining and confocal microscopy were used to visualize the microchannels. The results showed that microneedles created aqueous conduits of 50 ± 10 μm to deliver the microparticulate vaccine to the skin layers. Further, an in vivo comparison of immune response depicted significantly higher concentration of serum IgG, IgG2a, and B and T cell (CD4+ and CD8+) populations in the vaccinated animals than the control animals (p < 0.001). Upon challenge with live murine breast cancer cells, the vaccinated animals showed five times more tumor suppression than the control animals confirming the immune response activation and protection (p < 0.001). This research paves a way for individualized immunotherapy following surgical tumor removal to prolong relapse episodes.

摘要

乳腺癌影响着全球女性群体,是女性中第二常见的癌症。由于当前疗法存在各种局限性和不良反应,因此正在探索几种免疫疗法。开发有效的乳腺癌疫苗可以是一种具有开创性的免疫治疗方法。目前正在进行几项临床试验来评估这种方法。类似地,我们的研究旨在评估一种通过皮肤传递的颗粒状乳腺癌疫苗。这种颗粒状乳腺癌疫苗是通过喷雾干燥技术制备的,利用鼠乳腺癌全细胞裂解物作为肿瘤相关抗原的来源。颗粒状疫苗的平均粒径为 1.5μm,类似于病原体,从而有助于吞噬和抗原呈递,进而进一步激活免疫反应。使用市售的金属微针通过皮肤传递颗粒状疫苗。使用亚甲蓝染色和共聚焦显微镜来可视化微通道。结果表明,微针在皮肤层中创建了 50±10μm 的水导通道来传递微颗粒疫苗。此外,体内免疫反应比较表明,接种疫苗的动物血清 IgG、IgG2a 和 B 和 T 细胞(CD4+和 CD8+)群体的浓度明显高于对照组(p<0.001)。在受到活鼠乳腺癌细胞的挑战时,接种疫苗的动物比对照组动物显示出五倍的肿瘤抑制作用,证实了免疫反应的激活和保护(p<0.001)。这项研究为手术后肿瘤切除后的个体化免疫疗法铺平了道路,以延长复发期。

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