决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:CAR-T cell therapy in triple-negative breast cancer: Hunting the invisible devil.
三阴性乳腺癌(TNBC)被认为是乳腺癌中最复杂、最难治疗的亚型。
三阴性乳腺癌(TNBC)被认为是乳腺癌中最复杂、最难治疗的亚型。TNBC细胞不表达其他乳腺癌亚型所表达的众所周知的雌激素受体、孕激素受体和人表皮生长因子受体2(HER2)。这一现象使得包括内分泌治疗和HER2特异性抗体治疗在内的新型治疗方法无从下手。迄今为止,手术、放疗和全身化疗仍然是TNBC治疗的主要选择。然而,在许多病例中,这些方法要么临床获益甚微,要么无效,导致疾病复发和预后不良。如今,CAR-T 细胞疗法正日益成为治疗各种类型血液系统恶性肿瘤的一种选择。CAR-T是经过基因工程改造的T淋巴细胞,利用机体免疫系统机制选择性识别表达目标肿瘤相关抗原(TAA)的癌细胞并将其有效清除。然而,尽管CAR-T疗法在血液系统肿瘤中取得了临床成功,但CAR-T疗法在包括TNBC在内的实体瘤中面临的挑战要大得多。在这篇综述中,我们将讨论CAR-T疗法在血液系统肿瘤中的成功及其在实体瘤中的不足,然后总结在不同研究阶段中TNBC潜在的CAR-T可靶向TAA。
Triple-negative breast cancer (TNBC) is known as the most intricate and hard-to-treat subtype of breast cancer. TNBC cells do not express the well-known estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expressed by other breast cancer subtypes. This phenomenon leaves no room for novel treatment approaches including endocrine and HER2-specific antibody therapies. To date, surgery, radiotherapy, and systemic chemotherapy remain the principal therapy options for TNBC treatment. However, in numerous cases, these approaches either result in minimal clinical benefit or are nonfunctional, resulting in disease recurrence and poor prognosis. Nowadays, chimeric antigen receptor T cell (CAR-T) therapy is becoming more established as an option for the treatment of various types of hematologic malignancies. CAR-Ts are genetically engineered T lymphocytes that employ the body's immune system mechanisms to selectively recognize cancer cells expressing tumor-associated antigens (TAAs) of interest and efficiently eliminate them. However, despite the clinical triumph of CAR-T therapy in hematologic neoplasms, CAR-T therapy of solid tumors, including TNBC, has been much more challenging. In this review, we will discuss the success of CAR-T therapy in hematological neoplasms and its caveats in solid tumors, and then we summarize the potential CAR-T targetable TAAs in TNBC studied in different investigational stages.
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