肿瘤细胞治疗研究
英文原题：In Vivo CAR-T Therapy for Cancer Treatment: Mechanisms, Technological Advances, and Clinical Translation.
In Vivo CAR-T Therapy for Cancer Treatment: Mechanisms, Technological Advances, and Clinical Translation.
体内嵌合抗原受体（CAR）-T细胞疗法直接在体内重编程患者自身的T细胞，绕过了复杂且昂贵的传统制造过程。
体内嵌合抗原受体（CAR）-T细胞疗法直接在体内重编程患者自身的T细胞，绕过了复杂且昂贵的传统制造过程。这是通过系统性递送病毒或非病毒载体来实现的，这些载体对内源性T淋巴细胞进行基因修饰，从而从头产生功能性CAR-T细胞。通过消除体外细胞处理，该策略可以简化工作流程、降低成本、提高可及性，并实现更快的治疗。关键递送平台包括工程化慢病毒和腺相关病毒（AAV）载体，用于实现持久的CAR表达，以及靶向脂质纳米颗粒（LNPs），用于瞬时mRNA递送。生物材料支架和超声刺激等新兴技术进一步使局部和时空可控的T细胞工程成为可能。在临床上，复发/难治性多发性骨髓瘤和B细胞恶性肿瘤的早期试验已显示出强烈的抗肿瘤反应，即使没有预处理化疗。剩余挑战包括实现精确的T细胞靶向、克服免疫抑制性肿瘤微环境、防止抗原逃逸，以及管理载体基因毒性或LNP反应原性等安全风险。未来的转化将取决于联合协同方案、优化载体设计以及实施可调控的安全控制。本研究旨在强调体内CAR-T疗法如何从概念演变为临床现实，并有望将过继细胞疗法重新定义为一种可扩展且广泛适用的药理学干预措施。
In vivo Chimeric Antigen Receptor (CAR)-T cell therapy reprograms a patient's own T cells directly inside the body, bypassing the complex and costly traditional manufacturing process. This is achieved by systemically delivering viral or non-viral vectors that genetically modify endogenous T lymphocytes to produce functional CAR-T cells de novo . By eliminating ex vivo cell processing, this strategy can simplify workflows, reduce costs, improve accessibility, and allow faster treatment. Key delivery platforms include engineered lentiviral and adeno-associated viral (AAV) vectors for lasting CAR expression and targeted lipid nanoparticles (LNPs) for transient mRNA delivery. Emerging technologies like biomaterial scaffolds and ultrasound stimulation further enable localized and spatiotemporally controlled T cell engineering. Clinically, early trials in relapsed/refractory multiple myeloma and B-cell malignancies have shown strong antitumor responses, even without preconditioning chemotherapy. Remaining challenges comprise achieving precise T cell targeting, overcoming the immunosuppressive tumor microenvironment, preventing antigen escape, and managing safety risks such as vector genotoxicity or LNP reactogenicity. Future translation will depend on combining synergistic regimens, refining vector design, and implementing tunable safety controls. The aim of the study is to highlight how in vivo CAR-T therapy is evolving from concept to clinical reality, poised to redefine adoptive cell therapy as a scalable and widely applicable pharmacologic intervention.
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