同步自体过继T细胞免疫治疗对活动性COVID-19感染癌症患者化疗的临床影响

IF 2.8 2区 医学 Q3 IMMUNOLOGY
Congcong Li, Dazhao Xu, Linyao Lu, Shu Peng, Haiyang Zhao, Chuxiong Zeng, Lina Hu, Xianzhi Guo, Li Liu, Feifei Huo, Xiumei Rong, Zhenying Geng, Ping Lin, Xinna Zhou, Xiaoli Wang, Amy Hobeika, Michael A Morse, Herbert Kim Lyerly, Jun Ren
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引用次数: 0

摘要

背景:晚期癌症患者同时存在COVID-19感染,由于免疫功能受损不可避免地加重,死亡率增加。在这种情况下,用于抗癌治疗的自体过继T细胞免疫疗法(ACT)的作用和临床影响尚不清楚。同时使用ACT治疗晚期癌症患者活动性COVID-19感染的安全性和潜在的免疫重建尚不清楚。总结ACT输注对症状严重程度表现的影响。方法:在本临床观察研究中,根据常规治疗方案,分别从两个中心非随机入组患者,包括IV期癌症患者进行计划的ACT,化疗,有症状的COVID-19但未进行ACT的癌症患者,非癌症或非ACT但有症状的COVID-19感染病例。我们采用年龄调整的Charlson合并症指数(aCCI)来比较三组患者的预后。所有患者计划进行预定的标准抗癌治疗考虑,化疗加ACT计划以及支持治疗。主要目的是记录ACT对肿瘤患者外周血采血、树突状细胞(DC)和细胞因子诱导的杀伤T细胞(CIK-T)输注及随后共存的COVID-19感染后3个月内的临床疗效和影响。收集同期未进行ACT治疗和其他治疗的癌症病例,分别比较其严重程度和死亡率。结果:123例患者(ACT患者35例,非ACT患者23例,非癌患者65例)具有相似的aCCI。调整后入院的重症病例中,非癌症(26.2%,17/65)和非act癌症(52.2%,12/23)的COVID-19住院病死率与先前报道的数据相似。在ACT治疗期间,即使存在活动性COVID-19感染,也几乎没有重叠的不良反应。当暴露于ACT方案时,没有发生死亡病例(0/35)。接受ACT治疗的癌症患者的平均症状缓解时间比未接受ACT治疗和未接受ACT治疗的患者短(分别为4.46天比16.88天和17.90天),症状严重程度发生率也较低(P = 0.0010)。注射ACT对外周血计数无显著影响,而CD3-CD16+CD56+ NK细胞数量增加(P = 0.0017)。ACT输注量有利于增加症状由重向轻转变的可能性。结论:这些数据表明ACT输注活动性COVID-19患者的临床安全性。ACT对癌症患者的干预可产生症状缓解和恢复时间延长的益处。在这种传染性大流行期间,晚期癌症患者同时接受ACT治疗,可能同时利用和降低随后化疗并发症的免疫受损情况的风险。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Clinical impact of concurrent autologous adoptive T cells immunotherapy in active COVID-19 infected cancer patients for chemotherapy.

Clinical impact of concurrent autologous adoptive T cells immunotherapy in active COVID-19 infected cancer patients for chemotherapy.

Clinical impact of concurrent autologous adoptive T cells immunotherapy in active COVID-19 infected cancer patients for chemotherapy.

Clinical impact of concurrent autologous adoptive T cells immunotherapy in active COVID-19 infected cancer patients for chemotherapy.

Background: The concurrent presence of COVID-19 infection in advanced cancer patients has increased the mortality since the compromised immunity was inevitably worsen. The role and clinical impact of autologous adoptive T cell immunotherapy (ACT) designed for anti-cancer treatment were not known in such circumstances. The safety and potential immune reconstitution of concurrent ACT in advanced cancer patients with active COVID-19 infection have yet unknown as well. The effect of infused ACT on the symptom severity manifestation should be summarized.

Methods: In this respectively clinical observation study, patients were non-randomized enrolled from the two centers according to the regular therapeutic plans including stage IV cancer patients for scheduled ACT, chemotherapy, cancer patients with symptomatic COVID-19 but without ACT, neither cancer or non-ACT but symptomatic cases of COVID-19 infection. We have incorporated the age-adjusted Charlson comorbidity index (aCCI) for each patient to compare the prognosis of the three groups. All patients were planned for the scheduled standard anti-cancer therapeutic considerations, chemotherapy plus ACT as planned as well as the supportive care.The clinical efficacy and impact of ACT on cancer patients within the 3 months from the peripheral blood apheresis, dendritic cell (DC) and cytokine induced killer T cell (CIK-T ) infusion and subsequent co-existence of COVID-19 infection were recorded as the primary objective. During the same period, the cancer cases without ACT and others were collected to compare the occurrence of both severe and death rate respectively.

Results: There were 123 patients (35 of ACT, 23 of non-ACT, 65 of non-cancer) with similar aCCI. There were similar cohort-level COVID-19 in-hospital case fatality rates consistent with previously reported data for non-cancer (26.2%, 17/65) and non-ACT cancer (52.2%, 12/23) among those admitted severe cases after the adjustment.There were little overlapped adverse reactions during the ACT therapeutic period even in the presence of active COVID-19 infection. No death case was occurred (0/35) when those exposed to ACT regimen. Cancer patients receiving ACT had a shorter mean time to alleviation of symptoms compared with non-ACT and non-cancer (4.46 versus 16.88 and 17.90 days respectively) as well as the lowered severity incidence of symptoms (P = 0.0010). The infused ACT has not significant impact on peripheral blood count whereas the amount of CD3-CD16+CD56+ NK cells increased (P = 0.0017). The quantity of infused ACT was favorable for augmentation of possibility of severe to mild symptom shift.

Conclusions: These data demonstrate the clinical safety profiles while ACT infusions with active COVID-19 infection.The intervention of ACT for cancer patients could generate the benefit for symptom alleviation with improved recovery time. The concurrent ACT for advanced cancer patients during such infectious pandemic might simultaneously leverage and reduce the risk of immune compromised situation for subsequent chemotherapy complications.

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来源期刊
Infectious Agents and Cancer
Infectious Agents and Cancer ONCOLOGY-IMMUNOLOGY
CiteScore
5.80
自引率
2.70%
发文量
54
期刊介绍: Infectious Agents and Cancer is an open access, peer-reviewed online journal that encompasses all aspects of basic, clinical, epidemiological and translational research providing an insight into the association between chronic infections and cancer. The journal welcomes submissions in the pathogen-related cancer areas and other related topics, in particular: • HPV and anogenital cancers, as well as head and neck cancers; • EBV and Burkitt lymphoma; • HCV/HBV and hepatocellular carcinoma as well as lymphoproliferative diseases; • HHV8 and Kaposi sarcoma; • HTLV and leukemia; • Cancers in Low- and Middle-income countries. The link between infection and cancer has become well established over the past 50 years, and infection-associated cancer contribute up to 16% of cancers in developed countries and 33% in less developed countries. Preventive vaccines have been developed for only two cancer-causing viruses, highlighting both the opportunity to prevent infection-associated cancers by vaccination and the gaps that remain before vaccines can be developed for other cancer-causing agents. These gaps are due to incomplete understanding of the basic biology, natural history, epidemiology of many of the pathogens that cause cancer, the mechanisms they exploit to cause cancer, and how to interrupt progression to cancer in human populations. Early diagnosis or identification of lesions at high risk of progression represent the current most critical research area of the field supported by recent advances in genomics and proteomics technologies.
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