更新于：2024-04-29

Atezolizumab

阿替利珠单抗

更新于：2024-04-29

概要

概要

基本信息

药物类型

单克隆抗体

别名

Anti-PDL-1-Genentech/Roche、Atezolizumab (Genetical Recombination)、Atezolizumab (genetical recombination) (JAN)

+ [11]

靶点

PDL1

作用机制

PDL1抑制剂(程序性死亡配体1抑制剂)

治疗领域

肿瘤消化系统疾病呼吸系统疾病+ [12]

在研适应症

乳腺癌肺泡软组织肉瘤PD-L1阳性非小细胞肺癌+ [136]

非在研适应症

急性髓性白血病晚期乳腺癌晚期非小细胞肺癌+ [34]

原研机构

Genentech, Inc.Universitair Medisch Centrum Groningen

在研机构

Roche Registration GmbH

罗氏（中国）投资有限公司

Hoffmann-La Roche Ltd.

+ [12]

非在研机构

Rain Oncology, Inc.

香港大学

Pfizer Inc.

+ [5]

最高研发阶段批准上市

首次获批日期

美国 (2016-05-18),

尿路上皮癌

最高研发阶段(中国)批准上市

特殊审评突破性疗法 (美国)、快速通道 (美国)、加速批准 (美国)、孤儿药 (美国)、优先审评 (中国)、孤儿药 (澳大利亚)、优先审评 (澳大利亚)

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序列信息

Sequence Code 122091L

来源: *****

Sequence Code 4720027H

来源: *****

关联

849

项与阿替利珠单抗相关的临床试验

NCT05870800 / Not yet recruiting临床2期IIT

Phase II Open-Label Trial of Neoadjuvant Atezolizumab in Combination With CAPEOX for Resectable Non-Metastatic Proficient Mismatch Repair (PMMR) Colon Cancer

This is an open-label Phase II trial that will investigate the use of neoadjuvant CAPEOX chemotherapy with Atezolizumab followed by surgery and adjuvant chemotherapy for patients with localized resectable pMMR adenocarcinoma of the colon with a target accrual of 30 patients.
The investigators will explore if appropriately timed neoadjuvant CAPEOX with anti-PD-L1 mAb (Atezolizumab) can be administered safely and feasibly for 12 weeks, and that this combination will lead to improved clinical response associated with enhanced numbers of immune cells in surgically resected colon tumors.
Participants will receive 4 cycles of atezolizumab in combination with 4 cycles of CAPEOX (atezolizumab will be administered prior to chemotherapy) before standard of care surgical resection. Each cycle of neoadjuvant therapy is 3 weeks. Following surgery, participants still considered to be at high-risk of recurrence (per NCCN guidelines) will receive further adjuvant chemotherapy (mFOLFOX6 or CAPEOX),for 6 and 4 cycles respectively (for a total of 12 weeks), based on the discretion of the treating oncologist/investigator.
Participants will be followed up for an EFFICACY follow-up phase every 2 months during the first 6 months after surgery (months 1, 3, 6) and thereafter participants will enter a SURVIVAL follow-up phase and will be seen every 6 months starting at month 12 until month 36. During this the efficacy and survival follow up visits blood samples will be obtained for purposes of obtaining circulating DNA and stool and optional blood samples for storage for future exploratory analysis. Additionally, during these follow up visits, participants will be asked to complete quality of life questionnaires

开始日期2024-09-01

申办/合作机构

Baylor College of Medicine

[+1]

NCT06110572 / Recruiting临床1/2期IIT

(TESSERACT): Phase I/II Trial in ES-SCLC to Enhance Response to Atezolizumab Plus Chemotherapy With Total Body Irradiation (TBI)

This phase I/II trial studies the side effects, safety, and effectiveness of low dose radiation to the entire body (total body irradiation [TBI]) and higher dose radiation to known areas of cancer (hypofractionated radiation therapy [H-RT]) combined with atezolizumab and chemotherapy (carboplatin & etoposide) in treating patients with small cell lung cancer that has spread to disease sites outside of the lung (extensive stage). Extensive stage disease has historically been treated with chemotherapy alone with consideration of chest (thoracic) radiation therapy for those with response to chemotherapy, as well as consideration of preventative radiation therapy to the head (prophylactic cranial irradiation). Emerging evidence supports the synergistic interactions between immunotherapy and radiation therapy. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill tumor cells. Combining TBI and H-RT with atezolizumab and chemotherapy may improve response to treatment.

开始日期2024-07-31

申办/合作机构

The Vanderbilt-Ingram Cancer Center

[+1]

NCT06362252 / Not yet recruiting临床1/2期

A Phase 1b/2, Multicenter, Open-label Study of Ifinatamab Deruxtecan (I-DXd), a B7-H3 Antibody-Drug Conjugate (ADC), in Combination With Atezolizumab With or Without Carboplatin as First-line Induction or Maintenance, in Subjects With Extensive-stage Small Cell Lung Cancer (ES-SCLC) (IDeate-Lung03)

This study is designed to evaluate the safety and efficacy of ifinatamab deruxtecan (I-DXd) in combination with immune checkpoint inhibitor (ICI) atezolizumab with or without carboplatin in participants with extensive stage-small cell lung cancer (ES-SCLC) in the first-line (1L) setting.

开始日期2024-06-17

申办/合作机构

Daiichi Sankyo Co., Ltd.

[+1]

100 项与阿替利珠单抗相关的临床结果

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100 项与阿替利珠单抗相关的转化医学

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100 项与阿替利珠单抗相关的专利（医药）

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2,844

项与阿替利珠单抗相关的文献（医药）

2024-03-15·International Journal of Cancer

α‐FAtE: A new predictive score of response to atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma

Article

作者: Cascinu, Stefano ; Niizeki, Takashi ; Finkelmeier, Fabian ; Montes, Margarida ; Yasuda, Satoshi ; Ochi, Hironori ; Hiasa, Yoichi ; Tsuji, Kunihiko ; Kawata, Kazuhito ; Naganuma, Atsushi ; Itobayashi, Ei ; Presa, José ; Piscaglia, Fabio ; Kakizaki, Satoru ; Kariyama, Kazuya ; Okubo, Tomomi ; Vitiello, Francesco ; Nishimura, Takashi ; Casadei-Gardini, Andrea ; Scartozzi, Mario ; Takaguchi, Koichi ; Soldà, Caterina ; Bergamo, Francesca ; Hirooka, Masashi ; Lim, Ho Yeong ; Itokawa, Norio ; Toyoda, Hidenori ; Suda, Goki ; Vivaldi, Caterina ; Hatanaka, Takeshi ; Sakamoto, Naoya ; Amadeo, Elisabeth ; Nagano, Takuya ; Kosaka, Hisashi ; Nakamura, Shinichiro ; Steup, Christoph ; Morishita, Asahiro ; Kudo, Masatoshi ; Shimada, Noritomo ; Imai, Michitaka ; Kumada, Takashi ; Sho, Takuya ; Tada, Toshifumi ; Tada, Fujimasa ; Himmelsbach, Vera ; Iwamoto, Hideki ; Chon, Hong Jae ; Nishida, Naoshi ; Nouso, Kazuhiro ; Burgio, Valentina ; Kaibori, Masaki ; Koizumi, Yohei ; Rimini, Margherita ; Tani, Joji ; Persano, Mara ; Ohama, Hideko ; Tsutsui, Akemi ; Cheon, Jaekyung ; Tajiri, Kazuto ; Masi, Gianluca ; Shimose, Shigeo ; Fukunishi, Shinya ; Iavarone, Massimo ; Iijima, Hiroko ; Cabibbo, Giuseppe ; Hiraoka, Atsushi ; Aoki, Tomoko ; Atsukawa, Masanori ; Foschi, Francesco Giuseppe ; Rossari, Federico ; Ishikawa, Toru ; Yoo, Changhoon ; Ogawa, Chikara

Abstract:

Atezolizumab plus bevacizumab (AB) and lenvatinib can be alternatively used as first‐line systemic treatment of unresectable hepatocellular carcinoma (HCC). However, no direct comparison of the two regimens has been performed in randomized clinical trials, making the identification of baseline differential predictors of response of major relevance to tailor the best therapeutic option to each patient. Baseline clinical and laboratory characteristics of real‐world AB‐treated HCC patients were analyzed in uni‐ and multivariate analyses to find potential prognostic factors of overall survival (OS). Significant variables were incorporated in a composite score (α‐FAtE) and it was tested for specificity and sensitivity in receiver operating characteristic (ROC) curve and in multivariate analysis for OS. The score was applied in uni‐ and multivariate analyses for OS of a comparable lenvatinib‐treated HCC population. Finally, comparison between treatments was performed in patients with low and high α‐FAtE scores and predictivity estimated by interaction analysis. Time‐to‐progression (TTP) was a secondary endpoint. OS of AB‐treated HCC patients was statistically longer in those with α‐fetoprotein <400 ng/mL (HR 0.62, p = .0407), alkaline phosphatase (ALP) <125 IU/L (HR 0.52, p = .0189) and eosinophil count ≥70/μL (HR 0.46, p = .0013). The α‐FAtE score was generated by the sum of single points attributed to each variable among the above reported. In ROC curve analysis, superior sensitivity and specificity were achieved by the score compared to individual variables (AUC 0.794, p < .02). Patients with high score had longer OS (HR 0.44, p = .0009) and TTP (HR 0.34, p < .0001) compared to low score if treated with AB, but not with lenvatinib. Overall, AB was superior to lenvatinib in high score patients (HR 0.55, p = .0043) and inferior in low score ones (HR 1.75, p = .0227). At interaction test, low α‐FAtE score resulted as negative predictive factor of response to AB (p = .0004). In conclusion, α‐FAtE is a novel prognostic and predictive score of response to first‐line AB for HCC patients that, if validated in prospective studies, could drive therapeutic choice between lenvatinib and AB.

2024-02-01·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Pan-cancer analysis of PLAU indicates its potential prognostic value and correlation with neutrophil infiltration in BLCA

Article

作者: Zhang, Xiulan ; Jiang, Li ; Zhou, Jianda ; Yan, Wenguang ; Zhang, Jiaqi ; Shi, Ke ; Li, Man

BACKGROUND:

PLAU is known as a selected serine protease converting plasminogen to plasmin. The role of PLAU in the development of pan-cancer, especially bladder urothelial carcinoma (BLCA) remains unclear.

METHOD:

A variety of online tools and cancer databases, including TCGA, GETx, HPA database, GSCALite, UALCAN, ESTIMATE, CIBERSORT, ssGSEA algorithms and SangerBox website, were applied to investigate the associations between PLAU expression and prognosis, genetic alterations, pathway activation, and tumor immunity in pan-cancer. Through cBioPortal and STITCH platforms, the oncogenic role of PLAU and related targeting medicines in BLCA were also explored. We verified the expression of PLAU in pan-cancer cells and its function in bladder cancer cell lines using wet-lab experiments.

RESULTS:

PLAU expression levels were significantly higher in most cancer tissues. PLAU had a certain accuracy in the diagnosis of various types of cancers (90 % AUC > 0.700). In BLCA, PLAU has abundant methylated sites and showed statistical differences in clinical features. PLAU was involved in tumor immune infiltration, and especially positively correlated with neutrophil infiltration. High-expressed PLAU indicated poorer prognosis in the BLCA patients receiving Atezolizumab. A high mRNA and protein expression levels of PLAU were observed in pan-cancer cell lines, especially BLCA cells. Knockdown of PLAU inhibited the invasive, proliferative, and aggressive phenotypes of bladder cancer cells. Immunohistochemical staining validated PLAU's higher expression in BLCA tissues than in adjacent non-cancerous tissues. And overexpression of PLAU was associated with more advanced TNM stage, and high infiltrating depth.

CONCLUSION:

Our study revealed that PLAU can serve as a potential therapeutic target and prognostic marker for various malignancies, especially BLCA.

2024-02-01·JHEP Reports

A meta-analysis and real-world cohort study on the sex-related differences in efficacy and safety of immunotherapy for hepatocellular carcinoma

Article

作者: Masi, Gianluca ; Ulahannan, Susanna V ; Phen, Samuel ; Bettinger, Dominik ; Stauber, Rudolf ; von Felden, Johann ; Pinter, Matthias ; Singal, Amit G ; Che, Jaekyung ; Vogel, Arndt ; Pressiani, Tiziana ; Itani, Aleena ; Saeed, Anwaar ; Cammarota, Antonella ; Ang, Celina ; Chamseddine, Shadi ; Wege, Henning ; Huang, Yi-Hsiang ; Trauner, Michael ; Salani, Francesca ; Pomej, Katharina ; D'Alessio, Antonio ; Cortellini, Alessio ; Roig, Marta Bofill ; Kaseb, Ahmed ; Rimassa, Lorenza ; Fulgenzi, Claudia Angela Maria ; Pinato, David J ; Silletta, Marianna ; Wietharn, Brooke ; Kudo, Masatoshi ; Balcar, Lorenz ; Schulze, Kornelius ; Parikh, Neehar D ; Wu, Linda ; Parisi, Alessandro ; Nishida, Naoshi ; Lee, Pei-Chang ; Chon, Hong Jae ; Krall, Anja ; Samson, Adel ; Piscaglia, Fabio ; Abugabal, Yehia I ; Vivaldi, Caterina ; Galle, Peter R ; Meyer, Elias Laurin ; Stefanini, Bernardo ; Scheiner, Bernhard

Background & Aims:

Sex-related differences in the immune pathogenesis of hepatocellular carcinoma (HCC), particularly related to oestrogen-dependent secretion of pro-tumourigenic cytokines, are well-known. Whether sex influences the efficacy and safety of immunotherapy is not known.

Methods:

We performed a restricted maximum likelihood random effects meta-analysis of five phase III trials that evaluated immune checkpoint inhibitors (ICIs) in advanced HCC and reported overall survival (OS) hazard ratios (HRs) stratified by sex to evaluate sex-related differences in OS. In a real-world cohort of 840 patients with HCC from 22 centres included between 2018 and 2023, we directly compared the efficacy and safety of atezolizumab + bevacizumab (A+B) between sexes. Radiological response was reported according to RECIST v1.1. Uni- and multivariable Cox regression analyses were performed for OS and progression-free survival (PFS).

Results:

In the meta-analysis, immunotherapy was associated with a significant OS benefit only in male (pooled HR 0.79; 95% CI 0.73-0.86) but not in female (pooled HR 0.85; 95% CI 0.70-1.03) patients with HCC. When directly comparing model estimates, no differences in the treatment effect between sexes were observed. Among 840 patients, 677 (81%) were male (mean age 66 ± 11 years), and 163 (19%) were female (mean age 67 ± 12 years). Type and severity of adverse events were similar between the two groups. OS and PFS were comparable between males and females upon uni- and multivariable analyses (aHR for OS and PFS: 0.79, 95% CI 0.59-1.04; 1.02, 95% CI 0.80-1.30, respectively). Objective response rates (24%/22%) and disease control rates (59%/59%) were also similar between sexes.

Conclusion:

Female phase III trial participants experienced smaller OS benefit following ICI therapy for advanced HCC, while outcomes following A+B treatment were comparable between sexes in a large real-world database. Based on the ambiguous sex-related differences in survival observed here, further investigation of sex-specific clinical and biologic determinants of responsiveness and survival following ICIs are warranted.

Impact and implications:

While immune checkpoint inhibitors have emerged as standard of care for the treatment of hepatocellular carcinoma, there are conflicting reports on whether the efficacy of cancer immunotherapy differs between females and males. Our study suggests ambiguous sex-related differences in outcomes from immunotherapy in hepatocellular carcinoma. Further investigation of sex-specific clustering in clinicopathologic and immunologic determinants of responsiveness to immune checkpoint inhibitor therapy should be prioritised.

Systematic review registration:

PROSPERO CRD42023429625.

1,527

项与阿替利珠单抗相关的新闻（医药）

2024-04-25

·今日头条

胰腺癌生存期延长至6年！新型癌症疫苗有望根除微转移，预防复发

科学家成功研制出一款有潜力的治疗性疫苗，一名幸运的患者在接受这种全新的个体化 mRNA 疫苗后，迄今为止 3 年没有癌症协议！ 2020年9月，当芭芭拉·布里格姆（Barbara Brigham）被诊断出重症胰腺癌时，她的病情并不乐观。医生说：胰腺癌是最致命也是最难治疗的恶性肿瘤之一，5年总生存率约为8-10%，虽然早期患者可以手术切除，但 90% 的患者会在 7-9个月内大多数患者在放化疗或抑制免疫治疗后，生命进入倒计时！幸运的是，他的主治医生Balachandran博士现场推出了一种新型治疗性mRNA癌症疫苗的临床试验，当注射疫苗后，会训练身体免疫系统对癌细胞保持清醒。这可能会降低她的癌症的癌症风险。芭芭拉毫不犹豫地参加了这项临床试验，她和家人认为这是获得生存期最好的选择。 2020年10月，她接受了手术切除，手术后的肿瘤组织被送往实验室，研究人员进行了全面的基因测序，并筛选出最有效的目标基因，之后为芭芭拉“精准定制”了个性化的mRNA疫苗。芭芭拉共接受了9次疫苗注射，抗PD-L1疫苗atezolizumab以及6个月的化疗。芭芭拉也因此成为了这一重大获的国际最新研究成果的集体纪念者和参与者之一。幸运的是，在完成最后一次疫苗注射后的扫描结果显示：没有胰腺癌。在接受疫苗治疗三年后，这位77岁的老人激动地说“我感觉很好，目前还没有发现癌症，我非常感激能够接受它。机会和时机非常完美。它帮助了我，我希望它也能帮助别人。 ”最近目睹了她的大孙子大学毕业——她认为自己可能无法活着看到这一刻。胰腺癌患者保持3年无癌！新型mRNA癌症疫苗取得重大突破！ Autogene cevumeran是一种基于针对肿瘤患者个体化定制的个体化肿瘤疫苗。它是美国BioNTech公司强大的技术平台生成的个体化新产品疫苗，可以编码工件个体化新产品，可以激发人体针对肿瘤患者细胞产生全面的免疫反应，防止肿瘤细胞逃避免疫系统的攻击。最近I期临床试验是在美国纪念斯隆凯瑟琳癌症中心进行的，2023年5月10日公布了1.5年中位显示数据，并发表在国际重磅期刊《Nature》上引起巨大轰动。 2024年AACR大会上更新的3年认知数据持续显示，胰腺癌患者在手术后注射个体化mRNA癌症疫苗 Autogene cevumeran（代号为BNT122、RO7198457）进行辅助治疗，可延迟胰腺癌，研究还表明，在单次疫苗加强补充后，中位使用寿命可延长至6年！从2019年12月到2021年8月，共招募了34名胰腺癌患者，其中28名患者接受了手术。19名患者接受了atezolizumab治疗，其中16名患者接受了自体mRNA新疫苗cevumeran。 16名患者中有 15 名还接受了后续的 mFOLFIRINOX 化疗。结果显示：接受疫苗的 16 名患者中有 8 名 (50%) 产生了 T 细胞反应，并被认为是 mRNA 新疫苗cevumeran 的反应者。这意味着，疫苗接种了他们的免疫系统如何识别和清除免疫力，预防肿瘤。在有免疫反应的患者中，药物后3年内仍可检测到超过 80% 的疫苗诱导的新的提示T细胞。与无反应者（13.4个月）相比，这些患者的中位无载体生存期（达到达到）持续显着延长。对自体cevumeran有免疫反应的8名患者中有6名在三年内保持无疾病状态，而在试验期间对治疗没有免疫反应的8名患者有7名出现肿瘤血管。在血液测试中，所有8名反应者都产生了针对其肿瘤的T细胞，虽然进行了后续化疗，但这些被激活的、杀伤功能强大的T细胞在体内至少持续了2年。值得振奋的是，29号患者在第一次疫苗治疗后发现冠状转移病灶，但很快在第2次疫苗治疗后的影像检查中就消失了，这表明根据患者自身重组生产的mRNA新疫苗cevumeran可能具有根除肿瘤转移病灶的能力。最近由每周发起的研究还显示，在最初的 8 次启动剂量后，疫苗诱导的 T 细胞的中位数消耗量约为 1 年。然而，在单次疫苗接种加强后，这一中位数消耗量将延长至6年，研究人员表示，这只是一项小型研究，第一阶段只有16名患者。所以必须在更大规模的临床试验中检验因果关系。我们期待这款疫苗能有更卓越的数据出炉，早日上市让更多的癌症来自病人的噩梦。全球癌症疫苗遍地开花！终将成为人类攻克癌症的一把利剑！除了上述这款振奋人心的 mRNA 疫苗非常值得期待之外，特别值得一提的是目前均已大量晚期癌症患者开始接受癌症药物，甚至有一些患者在接受癌症药物治疗后，全身的转移灶完全消退。 2024年，全球癌症疫苗研发遍地开花，并取得了令人振奋的临床数据，已经引发新的关注一波肿瘤免疫治疗浪潮，有望成为新的抗癌利器，帮助无数患者战胜癌症！以下3款疫苗值得所有肿瘤患者关注：美国：癌症化疗及死亡风险降低44%！个体化癌症疫苗mRNA-4157启动Ⅲ期临床实验国际上大名鼎鼎的现代公司研发的在国际上皇冠的新型个体化癌症疫苗mRNA-4157是目前全球最值得期待的疫苗。这一款基于mRNA的疫苗类似国内研发的由编码多达34种新合成的mRNA组成，是一种针对晚期患者肿瘤定制的个体化肿瘤疫苗。最新临床数据显示：接受癌症疫苗mRNA-4157/V940联合PD-1（K药）作为辅助治疗，可将吊或死亡风险显着降低44% ！中国：晚期延迟完全持久缓解，国研癌症疫苗Neo-MoDC取得重大突破 2022年6月，国际重磅期刊《Nature》子刊上公布的一项新药品研究引起了巨大轰动。全新癌症疫苗是一种个性化的载有新药品的单核细胞衍生的树突状细胞疫苗，称为Neo-MoDC。一位晚期转移性患者首次接受了Neo-MoDC（个性化新抗原负载树突状细胞）疫苗和PD-1治疗后，病灶完全消失并持续长达数千年25个月，这是已知的第一个在中断中通过基于新的DC疫苗和PD-1治疗肿瘤实现完全和持久消退的研究成果，具有里程碑意义的里程碑！细胞疫苗取得重大突破！晚期癌症患者获得持久完全缓解！古巴：肺癌Cimavax疫苗有望延长生存期，预防预防！肺癌疫苗CIMAvax-EGF是由古巴分子免疫学中心经过25年，穷尽了第一代科学家的心血成功自主研发的全球首个注册的用于晚期非小细胞肺癌的治疗性疫苗，到底是来自美国全面封锁的就医压力，自主研发的疫苗，自给自足就够了，无意到一问世引起了全世界的轰动。 2023年4月，权威肿瘤学期刊《癌症》杂志上最新公布了肺癌疫苗作为晚期非小细胞肺癌患者治疗的真实世界研究数据，引起轰动！肺癌疫苗CIMAvax-EGF作为一种可耗竭肺癌EGF的免疫治疗对非小细胞肺癌患者中安全有效，显着延长了患者的生存期。好消息是国内患者现在可通过全球肿瘤医生网医学部向中国、日本或古巴医疗机构申请相关疫苗，标准配合延长治疗生存期，提高生活质量！目前癌症疫苗治疗是癌症免疫治疗领域最热门的研究方向，全球有数百个研究小组在组织攻关中，相信这些全新的个体化免疫治疗终将成为攻克人类癌症的新希望！参考资料： Rojas, LA、Sethna, Z.、Soares, KC 等人。个性化 RNA 新抗原疫苗可刺激胰腺癌中的 T 细胞。自然（2023）。 https://doi.org/10.1038/s41586-023-06063-y https://investors.biontech.de/news-releases/news-release-details/third-year-phase-1-follow-data-mrna-based-individualized/ https://www.aacr.org/about-the-aacr/newsroom/news-releases/immune-response-to-investigational-rna-vaccine-for-pancreatic-cancer-continues-to-correlate-with-clinical-益处/

疫苗AACR会议信使RNA临床结果临床1期

2024-04-25

·今日头条

益生菌凭实力出圈！开启肺癌、肝癌等全新模式，生存期竟达250天

在人体免疫系统中，除了我们熟知的淋巴组织外，还有一个容易被忽视的人体重要免疫器官，那就是“ 肠道 ”，人体70%左右的免疫细胞都聚集于此。若将人体视为一个“微生物王国”，那么肠道相当于“大都市”般的存在，其内蕴含百万亿的微生物群（包括真菌、病毒、细菌等），它们提供并维持宿主的健康，而这其中95%以上就是益生菌。益生菌是一类“活的、非病原性微生物”，可在适量情况下，为其宿主提供多种有益影响。既往多项研究发现，益生菌对提高机体免疫功能，改善肝癌、肺癌、肾癌、结直肠癌等多款癌种的预后，具有积极的效果，也将成为癌症和免疫治疗领域的热门研究方向之一！益生菌解锁肠道免疫密码，开启全新抗癌模式 ▲图源“摄图网” 肠道天然微生物群由大部分益生菌组成，包括双歧杆菌、乳杆菌、酵母菌、链球菌、大肠杆菌等诸多类型。人类自1907年开始食用益生菌以来，经过1个多世纪的筛选，目前占据主导地位的是双歧杆菌和乳酸菌。那么作为“肠道清道夫”的益生菌，如何开启全新抗癌模式呢？下面全球肿瘤医学部小编简单介绍一下，益生菌辅助抗癌的好处，以供参考。保护机体免受癌症侵害、降低癌症转移风险 1、抗癌作用：研究表明，益生菌通过调节肠道菌群、改善慢性炎症的免疫调节、结合和降解致癌化合物、降低肠道pH值、抑制产生潜在致癌化合物的酶、积极改变代谢活性、激活吞噬细胞等机制，发挥对抗肿瘤的作用。 2、降低特定癌种发生风险：益生菌利于维持肠道菌群平衡，将其作为生物标记物及操纵靶点，有助于降低肝癌、胰腺癌、结直肠癌、乳腺癌等特定癌种的发生风险。 3、预防癌变：益生菌还可促进抗炎细胞因子的生成，对预防正常细胞的癌变过程，具有重要意义。降低放化疗副作用 1、降低化疗产生的副作用化疗不仅会破坏机体的微生物组，增加感染的发生风险；还可能会造成肠道菌群失衡、黏膜炎、胃肠道反应（如便秘、恶心、厌食、腹泻、呕吐）等副作用，其中胃肠道反应尤为多见。因此积极开展肠道微生态（IM）检测，并辅助定制益生菌等措施，有助于改善化疗相关的胃肠道反应，提高患者治疗耐受度及生活质量。 2、降低放疗产生的副作用放疗（即放射治疗）是通过破坏癌细胞的DNA来杀伤肿瘤，放疗不仅会杀死癌细胞，同时也会在一定程度上损害正常组织。放疗常见的副作用主要包括两点，首先，会抑制机体细胞/体液的免疫功能，增加感染风险；其次，会造成肠道菌群失调、损伤胃肠黏膜屏障，从而可能引起胃肠道损伤、口腔黏膜炎等副作用。目前已有多款益生菌[如乳酸乳杆菌（BCMC12451）、长双歧杆菌（BCMC02120，BB-536）、屎肠杆菌、短乳杆菌CD2 等]，被证实可保护细菌菌群的生长，降低严重口腔黏膜炎的发生概率、降低口腔黏膜炎的严重程度。与其他抗癌方法联合应用 1、在免疫治疗过程中，适当进行益生菌的补充，有助于增强癌症患者的免疫功能。 2、传统抗癌手段（如放化疗），可能破坏患者的肠道微生物组。如果能适时补充益生菌，将有助于维持肠道内有益菌群的平衡。益生菌是把“双刃剑”，如何进行有效补充？虽然多项临床研究已证实益生菌对患者的免疫功能具有积极作用，但 2018年SITC的研究指出，只有在治疗前“安全”服用“合理的益生菌”，才能达到预期的应答水平！此处“合理的益生菌”指的是“由合理制造的活菌团组成”。然而市面上见到的益生菌可谓是琳琅满目，但其中的大部分可能并不适合癌症患者，原因如下： 1、并非同一物种的所有菌株都具有相同的特征，并且可能对生物体产生不同的影响。加之癌症的发病机制复杂，且不同患者所接受的治疗方案并不相同，故而不同菌株可能会产生不同的治疗效果。 2、不同患者的遗传背景、生活环境、饮食结构等存在较大差异，因此不同地区居民的肠道内所栖居的益生菌种类也有所不同，存在一定的个体差异性。 3、癌症患者往往存在中性粒细胞减少或免疫功能严重受损等异常情况，这些因素也可能会影响益生菌的选择及最终的治疗效果。 · 全球肿瘤医生网温馨提示 · 癌症患者在使用益生菌时，需要慎之又慎。建议在专业营养师或有执照的医疗保健人员的指导下，尽可能选择针对患者自身病情的“私人订制”版个体化益生菌，此类益生菌针对不同病种筛选出的特定菌种组成，可辅助肠道建立起优势菌种架构，并重整肠道环境，排除毒素及有害菌，促进病情的显著改善，以达到预期的应答水平。此外，益生菌的服用时间也需要特别注意，一般建议早晨空腹和睡前服用，疗效更佳。可提交资料至全球肿瘤医生网医学部了解定制益生菌。益生菌丁酸梭菌：治疗晚期非小细胞肺癌，中位无进展生存期长达250天丁酸梭菌是一种产芽孢杆菌，存在于土壤中，因其产生大量丁酸的能力而得名，可增加有益细菌，尤其是乳酸杆菌和双歧杆菌，其中，双歧杆菌可促进抗肿瘤免疫并促进ICB（免疫检查点抑制剂）的功效。丁酸梭菌MIYAIRI 588菌株（MIYA-BM）在中国和日本，被广泛用作益生菌疗法。日本熊本大学医院开展了一项针对“ 益生菌丁酸梭菌疗法（CBT）治疗晚期非小细胞肺癌 ”的临床研究，研究结果同步发表在《癌症免疫学研究（Cancer Immunology Research）》期刊中。本研究共入组118例晚期非小细胞肺癌（NSCLC）患者，中位年龄为68岁（包括99例男性、19例女性），大多患者（79%）的体能状态为0~1，接受过免疫检查点抑制剂（ICB，包括纳武单抗、派姆单抗或阿特珠单抗）作为一线/二线治疗。入组后，39例患者（33%）在开始ICB前和/或与ICI同时进行的6个月内，接受了益生菌丁酸梭菌疗法（CBT）。其中，9例（23%）在开始ICB前6个月内，接受益生菌CBT治疗；18例（46%）在ICB治疗前和治疗期间，接受益生菌CBT治疗；另有12例（31%）同时接受ICB与益生菌CBT治疗。结果显示： 1、中位总生存期（OS）：与不使用益生菌CBT相比，使用益生菌CBT患者的总生存期（OS）明显延长，中位OS 未达到（NR） vs 361天，P=0.009（详见下图）。 ▲图源“Cancer Immunol Res”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 2、中位无进展生存期（PFS）：中位PFS为 250天（使用益生菌CBT患者） vs 101天（不使用益生菌CBT患者），P=0.005（详见下图）。 ▲图源“Cancer Immunol Res”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除总之，上述结果表明，益生菌CBT显著延长了晚期非小细胞肺癌的总生存期（OS）和无进展生存期（PFS），对癌症患者ICB的治疗效果产生了积极影响。益生菌长双歧杆菌：提高肝细胞癌术后1年总生存率我国武汉曾开展过一项关于“ 口服含长双歧杆菌的益生菌混合物，促进肝细胞癌患者术后肝功能恢复 ”的开放、随机临床试验，该研究结果同步发表在世界权威期刊《Cell Host Microbe》上。在本研究中，入组169例患者，并将其随机分为两组，即益生菌（BL）组（83例患者，在围手术期服用含双歧杆菌的益生菌混合物）、对照（CON）组（86例患者，未给予益生菌混合物或任何其他益生菌补充剂治疗）。结果显示： 1、肝功能恢复情况：与对照组相比（ 33% ，86名患者中的28名延迟恢复），益生菌组术后延迟恢复（DR）患者显著减少（ 11% ，83名患者中仅有9名延迟恢复），这也意味着术后口服益生菌，有助于提高肝功能（LFR）正常患者的比例。 2、住院时间：对照组患者术后平均住院时间为 9.67天，而益生菌组患者仅为 8.34天。显然，与对照组相比，益生菌组患者住院时间明显缩短。 3、总生存期（OS）：截至2023年6月，术后1年的总生存期（OS），益生菌组明显长于对照组（详见下图）。 ▲图源“Cell Host&Microbe”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 4、益生菌丰度：使用16SrRNA扩增子测序证实，与AS-CON组（术后-对照组）相比，AS-BL组（术后益生菌组）中，益生菌（BL）的丰度有所增加（详见下图）。总之，上述研究结果表明，口服含有长双歧杆菌的益生菌混合物，可降低延迟康复率、缩短住院时间，并提高1年总体生存率。除了上文提到的肺癌、肝癌外，益生菌在治疗肾癌、结直肠癌、乳腺癌等其他实体瘤方面，也取得了积极的疗效。全球肿瘤医生网医学部之前做过相关报道，大家可阅读原文：益生菌竟能辅助抗癌，延长生存期、降低化疗副作用！惠及结直肠癌、肾癌、乳腺癌等。小编寄语随着癌症研究的不断深入，各类新兴热门研究疗法不断涌现，其中具有“精准”调控肠道菌群的活性益生菌等，有助于改善癌症患者的整体健康状况、提高免疫功能、增加治疗效果，同时降低放化疗等传统治疗的副作用，“小小的益生菌隐藏着巨大的抗癌能量”！《柳叶刀》子刊和《美国医学会杂志（JAMA）》也曾指出“个体化益生菌群，可能是未来的癌症免疫治疗策略”！参考资料 [1]Tomita Y,et al.Association of Probiotic Clostridium butyricum Therapy with Survival and Response to Immune Checkpoint Blockade in Patients with Lung Cancer. Cancer Immunol Res. 2020 Oct;8(10):1236-1242. https://aacrjournals.org/cancerimmunolres/article/8/10/1236/466810/Association-of-Probiotic-Clostridium-butyricum [2]Yu J,et al.Bifidobacterium longum promotes postoperative liver function recovery in patients with hepatocellular carcinoma. Cell Host Microbe. 2024 Jan 10;32(1):131-144.e6. https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(23)00461-4?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1931312823004614%3Fshowall%3Dtrue

微生物疗法放射疗法免疫疗法

2024-04-25

·BioSpace

Oncolytics Biotech® Announces Upcoming Presentations at the American Society of Clinical Oncology Annual Meeting

SAN DIEGO and CALGARY, AB, April 25, 2024 /PRNewswire/ -- Oncolytics Biotech, Inc. (NASDAQ: ONCY) (TSX: ONC), a leading clinical-stage company specializing in immunotherapy for oncology, today announced the acceptance of two abstracts at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, which is taking place from May 31 – June 4, 2024, in Chicago, Illinois. Details on the abstracts and poster presentation are shown below. Title: Phase 1/2 randomized, open-label, multicenter, Simon two-stage study of pelareorep combined with modified FOLFIRINOX +/- atezolizumab in patients with metastatic pancreatic ductal adenocarcinoma. Presentation Type: Poster Abstract Number: TPS4203 Session Title: Gastrointestinal Cancer – Gastroesophageal, Pancreatic, and Hepatobiliary Session Date and Time: June 1, 2024, 1:30 – 4:30 p.m. CT Title: Pelareorep driven blood TIL expansion in patients with pancreatic, breast and colon cancer. Presentation Type: Online abstract Abstract Number: e14625 Abstracts will be published on the ASCO Annual Meeting website at 5:00 p.m. ET on May 23, 2024. About Oncolytics Biotech Inc. Oncolytics is a clinical-stage biotechnology company developing pelareorep, an intravenously delivered immunotherapeutic agent. Pelareorep has demonstrated promising results in two randomized Phase 2 studies in metastatic breast cancer and Phase 1 and 2 studies in pancreatic cancer. It acts by inducing anti-cancer immune responses and promotes an inflamed tumor phenotype -- turning "cold" tumors "hot" -- through innate and adaptive immune responses to treat a variety of cancers. Pelareorep has demonstrated synergies with multiple approved oncology treatments. Oncolytics is currently conducting and planning combination clinical trials with pelareorep in solid and hematological malignancies as it advances towards registrational studies in metastatic breast cancer and pancreatic cancer, both of which have received Fast Track designation from the FDA. For further information, please visit: or follow the company on social media on LinkedIn and on X @oncolytics. Company Codes: NASDAQ-NMS:ONCY, Toronto:ONC

ASCO会议免疫疗法临床结果临床2期快速通道

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KEGG	Wiki	ATC	Drug Bank
D10773	阿替利珠单抗	L01XC32	DB11595

研发状态

适应症	最高研发状态	国家/地区	公司
三阴性乳腺癌	批准上市	欧盟更多	Roche Registration GmbH 更多
非小细胞肺癌	批准上市	挪威更多	Roche Registration GmbH 更多
转移性非小细胞肺癌	批准上市	美国更多	Genentech, Inc. 更多
转移性尿路上皮癌	批准上市	欧盟更多	Roche Registration GmbH 更多
输卵管癌	临床3期	瑞典更多	Hoffmann-La Roche, Inc. 更多

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03452137 (IMvoke010, AACR2024) 人工标引	临床3期	头颈部鳞状细胞癌	406	Atezolizumab 1200 mg	鏇艱糧製廠夢餘壓糧窪(憲範築壓蓋艱鏇憲構廠) = 範衊廠膚廠餘壓獵繭餘醖顧餘蓋窪鹹憲襯糧壓 (糧淵製鬱顧選糧鹹蓋夢, 46.5 ~ 46.5) 更多	不佳	2024-04-05
				Atezolizumab 1200 mg	鏇艱糧製廠夢餘壓糧窪(憲範築壓蓋艱鏇憲構廠) = 願鹽鬱鹽廠夢憲餘鹹範醖顧餘蓋窪鹹憲襯糧壓 (糧淵製鬱顧選糧鹹蓋夢, 46.5 ~ 46.5) 更多
NCT03359239 (phase I trial, AACR2024)	临床1期	尿路上皮癌辅助	9	Atezolizumab plus PGV-001	蓋築選積選鑰網築鹽憲(選餘範鏇願獵獵積獵壓) = 簾選觸鬱膚襯憲網鏇製鬱襯艱鬱壓鹹網積構醖 (鹽製範鑰遞襯衊築鬱齋 )	积极	2024-04-05
NCT03193190 (MORPHEUS-PDAC, AACR2024)	临床1/2期	胰腺导管腺癌一线 CD73 \| PD-L1	-	Atezolizumab + Etrumadenant + Chemotherapy	齋艱簾遞襯憲製製齋鏇(願窪廠齋網餘膚壓窪淵) = 蓋觸糧鹹觸餘簾製鏇願衊積壓願餘築醖憲衊齋 (鹽鏇築鏇選憲鑰蓋憲網 ) 更多	积极	2024-04-05
				Chemotherapy	齋艱簾遞襯憲製製齋鏇(願窪廠齋網餘膚壓窪淵) = 製衊艱鏇觸築壓壓鹹鬱衊積壓願餘築醖憲衊齋 (鹽鏇築鏇選憲鑰蓋憲網 ) 更多
NCT04458922 (AACR2024)	临床2期	软骨肉瘤 \| 透明细胞肉瘤 PD-L1+ \| CD8+ \| CD3ζ pY142+	9	Atezolizumab 1200 mg/m2	獵積繭壓願鏇構廠製壓(淵糧願鹹糧膚憲夢壓廠) = 膚鑰鏇淵繭衊顧壓繭糧觸夢觸製顧蓋願醖鑰齋 (艱獵獵製淵衊繭選衊艱 ) 更多	-	2024-04-05
NCT02486718 (IMpower010, AACR2024)	临床3期	非小细胞肺癌IIIA期辅助	233	Atezolizumab 1200 mg q3w	艱襯襯製窪衊鑰簾願齋(鏇顧齋淵製齋憲衊夢選): HR = 0.73 (95% CI, 0.28 ~ 1.88) 更多	积极	2024-04-05
				atezolizumab
AACR2024	N/A	肝癌 immune signature scores (ISS)	-	Atezolizumab plus bevacizumab	壓廠襯齋簾淵鑰鑰觸鏇(遞繭網襯構壓範遞窪鏇) = 遞淵鏇獵齋壓憲憲廠鬱憲製範構艱鏇遞顧獵糧 (淵獵網膚願鑰願襯簾顧 )	积极	2024-04-05
				Sorafenib	壓廠襯齋簾淵鑰鑰觸鏇(遞繭網襯構壓範遞窪鏇) = 構餘夢糧鏇築觸觸鏇簾憲製範構艱鏇遞顧獵糧 (淵獵網膚願鑰願襯簾顧 )
NCT02928406 (CTgov)	临床3期	肾盂输尿管移行细胞癌转移 \| 泌尿系统肿瘤	1,004	atezolizumab	鏇鏇襯膚淵糧製壓鑰廠(憲遞積觸鏇鬱憲夢壓積) = 齋網選顧觸製糧壓觸繭鏇簾艱範鬱願簾齋壓鹹 (衊廠膚醖觸鑰積廠願鹹, 網壓鹹製窪襯製醖壓糧 ~ 製鏇膚製繭餘獵築衊獵) 更多	-	2024-04-04
NCT03519295 (SCARCE C17-02 PRODIGE 60, Pubmed)	临床2期	肛门肿瘤一线 PD-L1 combined positive score of 5 or greater	97	Atezolizumab plus mDCF	壓鹽餘築糧壓憲鬱顧膚(醖觸積醖餘衊繭衊醖鹹) = 淵築夢夢鬱簾襯範繭襯餘構製選築簾鑰獵膚蓋 (壓顧壓醖膚淵獵遞鏇鹽, 35 ~ 55) 更多	不佳	2024-04-01
				mDCF alone	壓鹽餘築糧壓憲鬱顧膚(醖觸積醖餘衊繭衊醖鹹) = 範顧築繭製網壓壓壓簾餘構製選築簾鑰獵膚蓋 (壓顧壓醖膚淵獵遞鏇鹽, 29 ~ 58) 更多
NCT04471428 (CONTACT-01, Pubmed)	临床3期	转移性非小细胞肺癌	366	Atezolizumab + Cabozantinib	膚衊壓顧鹹鹽蓋製壓鹽(選廠積夢廠觸齋願選醖) = occurred in 39.5% vs 34.7% of patients receiving Atezolizumab + Cabozantinib vs Docetaxel 艱範鹽糧製廠窪顧構膚 (選壓餘積窪憲構艱網衊 ) 更多	不佳	2024-03-29
				Docetaxel
NCT04177108 (CTgov)	临床3期	三阴性乳腺癌	242	Paclitaxel+Atezolizumab+Ipatasertib (Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel)	顧願夢淵窪築淵願襯積(築簾糧鹽艱餘網選襯膚) = 築觸繭夢製繭窪鏇繭醖構蓋願淵築築鑰構繭壓 (壓獵獵淵網鑰襯製憲鏇, 蓋鏇襯鏇鬱選積範鑰鏇 ~ 餘膚積蓋淵獵願衊衊簾) 更多	-	2024-03-27
				Paclitaxel+Atezolizumab+Ipatasertib (Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel)	顧願夢淵窪築淵願襯積(築簾糧鹽艱餘網選襯膚) = 鏇簾壓獵顧膚選選築構構蓋願淵築築鑰構繭壓 (壓獵獵淵網鑰襯製憲鏇, 網觸顧遞艱網範簾製範 ~ 築鬱齋衊網積淵築淵簾) 更多