Department of Dermatology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany.
Comprehensive Cancer Center Erlangen European Metropolitan Area of Nuremberg (CCC ER-EMN), Erlangen, Germany.
Front Immunol. 2023 Sep 6;14:1248867. doi: 10.3389/fimmu.2023.1248867. eCollection 2023.
The treatment of cancer was revolutionized within the last two decades by utilizing the mechanism of the immune system against malignant tissue in so-called cancer immunotherapy. Two main developments boosted cancer immunotherapy: 1) the use of checkpoint inhibitors, which are characterized by a relatively high response rate mainly in solid tumors; however, at the cost of serious side effects, and 2) the use of chimeric antigen receptor (CAR)-T cells, which were shown to be very efficient in the treatment of hematologic malignancies, but failed to show high clinical effectiveness in solid tumors until now. In addition, active immunization against individual tumors is emerging, and the first products have reached clinical approval. These new treatment options are very cost-intensive and are not financially compensated by health insurance in many countries. Hence, strategies must be developed to make cancer immunotherapy affordable and to improve the cost-benefit ratio. In this review, we discuss the following strategies: 1) to leverage the antigenicity of "cold tumors" with affordable reagents, 2) to use microbiome-based products as markers or therapeutics, 3) to apply measures that make adoptive cell therapy (ACT) cheaper, e.g., the use of off-the-shelf products, 4) to use immunotherapies that offer cheaper platforms, such as RNA- or peptide-based vaccines and vaccines that use shared or common antigens instead of highly personal antigens, 5) to use a small set of predictive biomarkers instead of the "sequence everything" approach, and 6) to explore affordable immunohistochemistry markers that may direct individual therapies.
在过去的二十年中,通过利用免疫系统针对恶性组织的机制,即所谓的癌症免疫疗法,癌症的治疗发生了革命性的变化。两种主要的发展推动了癌症免疫疗法:1)使用检查点抑制剂,其特点是在实体瘤中主要具有相对较高的反应率,但代价是严重的副作用;2)使用嵌合抗原受体(CAR)-T 细胞,在治疗血液恶性肿瘤方面表现出非常高的效率,但迄今为止在实体瘤中尚未显示出高临床疗效。此外,针对个体肿瘤的主动免疫正在出现,第一批产品已获得临床批准。这些新的治疗选择非常昂贵,在许多国家的健康保险中都没有得到补偿。因此,必须制定策略使癌症免疫疗法负担得起,并提高成本效益比。在这篇综述中,我们讨论了以下策略:1)利用负担得起的试剂增强“冷肿瘤”的抗原性;2)使用基于微生物组的产品作为标志物或治疗剂;3)应用使过继细胞疗法(ACT)更便宜的措施,例如使用现成产品;4)使用提供更便宜平台的免疫疗法,例如基于 RNA 或肽的疫苗和使用共享或常见抗原而不是高度个性化抗原的疫苗;5)使用一小套预测性生物标志物代替“全面测序”方法;6)探索负担得起的免疫组织化学标志物,这些标志物可能指导个体化治疗。