首次CAR - T治疗晚期前列腺癌人体试验

用免疫疗法治疗前列腺癌目前很难做到。

Treating prostate cancer with immunotherapy is currently difficult to do.

但是，根据发表在《自然医学》杂志上的一期试验研究，美国最大的癌症研究和治疗机构之一City of Hope的研究人员开发的一种嵌合抗原受体(CAR) T细胞疗法的首次人体一期试验结果显示，晚期前列腺癌患者可以安全地使用细胞免疫疗法治疗，治疗效果良好。

But results from a first in-human phase 1 trial using a chimeric antigen receptor (CAR) T cell therapy developed by researchers from City of Hope, one of the largest cancer research and treatment organizations in the United States, showed that patients with advanced prostate cancer can be treated safely with the cellular immunotherapy with promising therapeutic activity, according to the phase 1 trial study published today in Nature Medicine.

该试验使用CAR - T细胞疗法治疗了14名前列腺干细胞抗原(PSCA)阳性的转移性去势抵抗性前列腺癌(mCRPC)患者，这些患者已经扩散到前列腺之外，对激素治疗不再有反应。

The trial treated 14 prostate stem cell antigen (PSCA)-positive patients who had metastatic castration resistant prostate cancer (mCRPC), which had spread beyond the prostate and no longer responded to hormone treatment, using CAR T cell therapy.

在美国，每年有超过34000名男性死于这种类型的前列腺癌。

More than 34,000 men with this type of prostate cancer die each year in the United States.

前列腺癌被称为免疫沙漠，很难用免疫疗法来治疗，因为肿瘤内部没有很多T细胞。

Prostate cancer has been called an immune desert; the tumor microenvironment is difficult to treat with immunotherapies because you don't get a lot of T cells inside the tumor.

患者接受了1亿个CAR - T细胞的单次输注，之前没有进行淋巴细胞清除化疗。由于这是首次人体CAR - T细胞试验，因此单独评估CAR - T细胞在患者中的安全性非常重要。

Patients received a single infusion of 100 million CAR T cells without prior lymphodepletion chemotherapy. Since this was a first-in-human CAR T cell trial, it was important to assess the safety of CAR T cells alone in patients.

在相同的CAR - T细胞剂量和淋巴细胞清除的情况下，存在膀胱炎或膀胱刺激的剂量限制性毒性副作用。多尔夫解释说，PSCA也存在于膀胱中，因此CAR - T细胞很可能会攻击膀胱细胞，引起炎症。

At that same CAR T cell dose and with lymphodepletion, there was a side effect of dose-limiting toxicity of cystitis, or irritation of the bladder. Dorff explained that PSCA is also found in the bladder so the CAR T cells most likely attacked the bladder cells, causing inflammation.

研究人员随后在研究中加入了一个新的队列，使用部分淋巴细胞清除的方法来减轻这种毒性。

Researchers then added a new cohort to the study using reduced lymphodepletion, which mitigated this toxicity.

14名患者中有4名患者的PSA水平下降，PSA水平是前列腺癌患者疾病进展的血清标志物，其中一名患者PSA水平明显下降。影像显示在一部分接受治疗的患者中有治疗反应。

Four out of 14 patients had declines in their PSA levels, which is a serum marker of disease progression in people with prostate cancer, including one patient with a significant decline. Imaging showed therapeutic responses in a subset of treated patients.

14例患者中有5例有轻度或中度细胞因子释放综合征。

Five out of 14 patients had mild or moderate cytokine release syndrome.

在28天的监测期内，CAR - T细胞并没有维持在高水平，这限制了治疗的有效性。这在实体肿瘤CAR - T细胞领域的一个共同的挑战。

CAR T cells did not persist at high levels beyond the 28-day monitoring period, which limits the therapy's effectiveness. This presented a common challenge in the solid tumor CAR T cell field .

Journal reference:

Dorff, T. B., et al. (2024). PSCA-CAR T cell therapy in metastatic castration-resistant prostate cancer: a phase 1 trial. Nature Medicine. doi.org/10.1038/s41591-024-02979-8.