Division of Early Drug Development and Innovative Therapy, European Institute of Oncology IRCCS, Milan, Italy.
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Expert Opin Investig Drugs. 2022 Jun;31(6):499-513. doi: 10.1080/13543784.2021.1972968. Epub 2021 Sep 26.
Immunotherapy through the blockade of PD1-PDL1 axis has shown to improve outcomes in advanced and early triple negative breast cancer (TNBC). To further enhance immune-stimulation, and ultimately improve patient outcomes, a wide variety of next-generation immunotherapies (NGIO) is being developed for this disease.
In the present article, we discuss the immune landscape of TNBC and recapitulate the rationale and available clinical evidence of NGIO under early phase development for TNBC, highlighting challenges and opportunities in this emerging field of research.
Multiple immunotherapeutic strategies beyond PD-(L)1 blockade have been tested for TNBC, including the targeting of further inhibitory checkpoints, the agonism of costimulatory molecules, the intratumoral administration of immunotherapies and cancer vaccines. Most of these strategies have demonstrated to be safe in early clinical trials, with some exhibiting early signs of antitumor activity. To optimally harness the potential of NGIO, a refined patient selection based on emerging immune biomarkers will be required, through an adaptation of immunotherapeutic strategies based on patient and tumor characteristics. More mature data from ongoing clinical trials, added to the progressively increasing knowledge on breast cancer immune landscape, will hopefully clarify the role of NGIO for the treatment of TNBC.
通过阻断 PD1-PDL1 轴的免疫疗法已显示出可改善晚期和早期三阴性乳腺癌(TNBC)的疗效。为了进一步增强免疫刺激,最终改善患者的预后,正在为这种疾病开发各种下一代免疫疗法(NGIO)。
在本文中,我们讨论了 TNBC 的免疫景观,并回顾了处于早期开发阶段的用于 TNBC 的 NGIO 的原理和现有临床证据,强调了这一新兴研究领域的挑战和机遇。
除了 PD-(L)1 阻断之外,已经针对 TNBC 测试了多种免疫治疗策略,包括针对进一步抑制性检查点的靶向治疗、共刺激分子的激动剂、免疫疗法和癌症疫苗的肿瘤内给药。这些策略中的大多数在早期临床试验中已被证明是安全的,其中一些显示出早期抗肿瘤活性的迹象。为了最大限度地发挥 NGIO 的潜力,需要根据新兴的免疫生物标志物对患者进行精细选择,通过基于患者和肿瘤特征的免疫治疗策略的适应性调整。来自正在进行的临床试验的更成熟数据,加上对乳腺癌免疫景观的不断增加的知识,有望阐明 NGIO 在治疗 TNBC 中的作用。