Smolarska Anna, Kokoszka Zuzanna, Naliwajko Marcelina, Strupczewska Julia, Tondera Jędrzej, Wiater Maja, Orzechowska Roksana
Center of Cellular Immunotherapies, Warsaw University of Life Sciences, 02-787 Warsaw, Poland.
Faculty of Biology and Biotechnology, Warsaw University of Life Sciences, 02-787 Warsaw, Poland.
Int J Mol Sci. 2025 Jun 9;26(12):5524. doi: 10.3390/ijms26125524.
Solid tumors pose significant therapeutic challenges due to their resistance to conventional treatments and the complexity of the tumor microenvironment. Cell-based immunotherapies offer a promising approach, enabling precise, personalized treatment through immune system modulation. This review explores several emerging cellular therapies for solid tumors, including tumor-infiltrating lymphocytes, T cell receptor-engineered T cells, CAR T cells, CAR natural killer cells, and macrophages. Tumor-infiltrating lymphocytes and their modified versions, T cell receptor-engineered T cells and CAR T cells, provide personalized immune responses, although their effectiveness can be limited by factors like variation in tumor antigens and the suppressive nature of the tumor environment. Natural killer cells engineered with chimeric receptors offer safer, non-major histocompatibility complex-restricted targeting, while modified macrophages exploit their natural ability to enter tumors and reshape the immune landscape. CAR-modified macrophages and macrophages conjugated with drugs are also considered as therapy for solid tumors. The review also examines the implications of autologous versus allogeneic cell sources. Autologous therapies ensure immunologic compatibility but are limited by scalability and manufacturing constraints. Allogeneic approaches offer "off-the-shelf" potential but require gene editing to avoid immune rejection. Integrating synthetic biology, gene editing, and combinatorial strategies will be essential to enhance efficacy and expand the clinical utility of cellular immunotherapies for solid tumors.
实体瘤由于对传统治疗具有抗性以及肿瘤微环境的复杂性，给治疗带来了重大挑战。基于细胞的免疫疗法提供了一种有前景的方法，能够通过调节免疫系统实现精确的个性化治疗。本文综述探讨了几种针对实体瘤的新兴细胞疗法，包括肿瘤浸润淋巴细胞、T细胞受体工程化T细胞、嵌合抗原受体T细胞（CAR T细胞）、CAR自然杀伤细胞和巨噬细胞。肿瘤浸润淋巴细胞及其改良版本，即T细胞受体工程化T细胞和CAR T细胞，可提供个性化免疫反应，尽管其有效性可能会受到肿瘤抗原变异和肿瘤环境抑制性等因素的限制。经嵌合受体工程改造的自然杀伤细胞提供了更安全的、不受主要组织相容性复合体限制的靶向作用，而经过改造的巨噬细胞则利用其进入肿瘤并重塑免疫格局的天然能力。CAR修饰的巨噬细胞以及与药物偶联的巨噬细胞也被视为实体瘤的治疗方法。本文综述还探讨了自体与异体细胞来源的影响。自体疗法可确保免疫相容性，但受到可扩展性和生产限制的制约。异体方法具有“现货供应”的潜力，但需要基因编辑以避免免疫排斥。整合合成生物学、基因编辑和联合策略对于提高实体瘤细胞免疫疗法的疗效并扩大其临床应用至关重要。
