基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
过继性自然杀伤(NK)细胞疗法是治疗三阴性乳腺癌的一种有前景的策略,但其疗效往往受到瘤内持久性差以及在免疫抑制性肿瘤微环境中功能耗竭的限制。
英文原题:Tumor-infiltrating lymphocyte transfusion in a patient with treatment refractory triple negative breast cancer.
该病例在所选治疗方式上具有独特性和特殊性,因为患者所患疾病极为难治。
背景:三阴性乳腺癌(TNBC)具有侵袭性,常采用化疗治疗。近年来,治疗方案中加入了程序性死亡蛋白1(PD-1)抑制剂和抗体药物偶联物,但转移性疾病仍致命。采用TIL(肿瘤浸润淋巴细胞)的过继性细胞治疗(ACT)在黑色素瘤中已有充分研究,但在其他实体瘤中的数据较少。 病例:本文介绍一例31岁患者,诊断为BRCA1阳性TNBC。患者在标准治疗期间疾病迅速进展。因此,研究者进一步对肿瘤进行基因检测,发现BRCA1杂合性缺失、TP53双重突变和MYC扩增。由于对常规治疗耐药,患者于2021年11月在Hadassah大学医学中心接受了使用TIL的实验性治疗。治疗期间,患者自述临床状况有所改善,包括一个月无需住院。然而,患者最终离世,推测与白细胞介素2(IL-2)毒性有关。 结论:该病例因患者疾病极度难治及所选治疗方式而具有独特性。标准治疗迅速失败后,尝试输注TIL进行过继性细胞治疗。该治疗已证实对黑色素瘤有效,但其他实体瘤(包括TNBC)的数据极其有限。尽管患者最终可能因治疗副作用离世,但曾出现短暂临床获益。仍需进一步研究。
BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive form of breast cancer that is treated with chemotherapy. Recently, programmed death 1 (PD1) inhibition, as well as antibody-drug conjugates, have been added to the available treatment regimen, yet metastatic disease is fatal. Adoptive cell therapy (ACT) using tumor infiltrating lymphocytes (TILs) has been well described in melanoma, but less data is available on other solid malignancies. CASE: Herein, we present a case of a 31-year-old patient diagnosed with Breast Cancer gene 1 (BRCA1) positive, TNBC. The patient's disease rapidly progressed while under standard treatment protocols. As a result, additional genetic testing of the tumor was carried out and revealed loss of BRCA1 heterozygosity, a double Tumor Protein 53 (TP53) mutation, and MYC amplification. Due to resistance to conventional therapy, an experimental approach was attempted using tumor-infiltrating lymphocytes in November 2021 at Hadassah University Medical Center. While receiving this treatment, the patient exhibited a reported subjective clinical improvement including a month spent out of the hospital. However, the final result, presumably due to Interleukin 2 (IL-2) toxicity, was the patient's passing. CONCLUSION: This case is unique and peculiar regarding the treatment modality chosen, due to the extremely refractory disease the patient suffered from. After standard therapies rapidly failed, adoptive cell therapy was attempted with the infusion of TILs. This treatment has been shown effective in melanoma, however, there is an extreme paucity of data on other solid tumors, including TNBC. Although the patient ultimately demised presumably due to treatment side effects, brief clinical benefit was apparent. Further studies are warranted.
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