CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Vaccine-like nanomedicine for cancer immunotherapy.
Vaccine-like nanomedicine for cancer immunotherapy.
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免疫检查点阻断(ICB)和CAR-T 细胞疗法的成功临床应用引发了对免疫疗法的广泛关注;然而,这些疗法特异性和持续性有限且具有毒性,未达到高效癌症治疗的预期。治疗性癌症疫苗可指导免疫系统捕获肿瘤特异性抗原、产生长期免疫记忆并特异性清除癌细胞,正逐渐成为最有前景的肿瘤根除策略。但部分现有疫苗免疫原性弱、体内稳定性不足,限制了其发展。近期纳米技术被用于疫苗制备,在癌症免疫治疗中显示出良好效果。纳米颗粒可提高疫苗稳定性;其纳米级尺寸促进吞噬细胞内化抗原,从而增强抗原识别和呈递。表面修饰靶向单元还可使疫苗递送至特定细胞。
同时,具有佐剂效应的纳米载体可提高疫苗疗效。除由抗原和佐剂组成的经典疫苗外,纳米颗粒介导的化疗、放疗及某些其他疗法可诱导肿瘤抗原原位释放,从而有效模拟抗肿瘤免疫应答。这类类疫苗纳米药物不仅能杀伤原发肿瘤,还可预防肿瘤复发并帮助清除转移瘤。本文介绍用于抗原递送和原位抗肿瘤疫苗接种的纳米颗粒递送系统最新进展,并讨论纳米疫苗在癌症治疗临床转化中的机遇和挑战。
The successful clinical application of immune checkpoint blockade (ICB) and chimeric antigen receptor T cells (CAR-T) therapeutics has attracted extensive attention to immunotherapy, however, their drawbacks such as limited specificity, persistence and toxicity haven't met the high expectations on efficient cancer treatments.
Therapeutic cancer vaccines which instruct the immune system to capture tumor specific antigens, generate long-term immune memory and specifically eliminate cancer cells gradually become the most promising strategies to eradicate tumor.
However, the disadvantages of some existing vaccines such as weak immunogenicity and in vivo instability have restricted their development. Nanotechnology has been recently incorporated into vaccine fabrication and exhibited promising results for cancer immunotherapy.
Nanoparticles promote the stability of vaccines, as well as enhance antigen recognition and presentation owing to their nanometer size which promotes internalization of antigens by phagocytic cells. The surface modification with targeting units further permits the delivery of vaccines to specific cells. Meanwhile, nanocarriers with adjuvant effect can improve the efficacy of vaccines.
In addition to classic vaccines composed of antigens and adjuvants, the nanoparticle-mediated chemotherapy, radiotherapy and certain other therapeutics could induce the release of tumor antigens in situ, which therefore effectively simulate antitumor immune responses. Such vaccine-like nanomedicine not only kills primary tumors, but also prevents tumor recurrence and helps eliminate metastatic tumors.
Herein, we introduce recent developments in nanoparticle-based delivery systems for antigen delivery and in situ antitumor vaccination.
We will also discuss the remaining opportunities and challenges of nanovaccine in clinical translation towards cancer treatment.
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