A Phase 1a/1b, Open-label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Anti-neoplastic Activity of S095029 (Anti-NKG2A) as Monotherapy and in Combination With Sym021 (Anti-PD-1) in Patients With Advanced Solid Tumor Malignancies Followed by an Expansion Part With Triplet Combinations of S095029 and Sym021 and an Anti-HER2 mAb or Anti-EGFR mAbs (Futuximab/Modotuximab) in Patients With Metastatic Gastric or Colorectal Cancers

The purpose of the study is to investigate the safety, tolerability, and preliminary anti-neoplastic activity of S095029 alone and in combination with Sym021 in patients with advanced solid tumor malignancies followed by an expansion phase of triple combinations.
*The study sponsor has made the decision not to move forward to the expansion part of the study due to strategic considerations, unrelated to any safety issues or concerns. The study will be stopped after completion of dose escalation parts 1a and 1b of the study.

开始日期2021-10-15

申办/合作机构

Institut de Recherches Intern Servier

[+1]

NCT04195373

/ Withdrawn临床1期

A Phase I Open-label, Safety Study of Intra-tumoral Application of TMV-018 in Combination With 5-FC or Anti-PD-1 Therapy in Patients With Tumors of the Gastrointestinal Tract

This study aims to determine the safety and tolerability of TMV-018 when given alone or in combination with the prodrug 5-Fluorocytosine (5-FC) or an anti-PD-1 checkpoint inhibitor in patients with gastrointestinal tumors. Furthermore, the maximum tolerated dose (MTD) and recommended Phase II dose of TMV-018 shall be determined.

开始日期2020-11-23

申办/合作机构

Themis Bioscience GmbH

[+2]

NCT04672434

/ Completed临床1期

A Phase 1, Open-Label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Antineoplastic Activity of Sym024 (Anti-CD73) as Monotherapy and in Combination With Sym021 (Anti-PD-1) in Patients With Advanced Solid Tumor Malignancies

The primary purpose of this study is to see if Sym024 is safe and tolerable as monotherapy and in combination with Sym021 in patients with solid tumor malignancies.

开始日期2020-11-19

申办/合作机构

Symphogen A/S

100 项与 Sym-021 相关的临床结果

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100 项与 Sym-021 相关的转化医学

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100 项与 Sym-021 相关的专利（医药）

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项与 Sym-021 相关的文献（医药）

2024-09-20·Nan fang yi ke da xue xue bao = Journal of Southern Medical University

[High RNF7 expression enhances PD-1 resistance of non-small cell lung cancer cells by promoting CXCL1 expression and myeloid-derived suppressor cell recruitment via activating NF-κB signaling].

Article

作者: Zhong, N ; Geng, B ; Sun, Z ; Zhao, W ; Wang, H

OBJECTIVE:

To investigate the mechanism of RNF7 for regulating myeloid-derived suppressor cells (MDSCs) in nonsmall cell lung cancer (NSCLC).

METHODS:

TIMER2.0 database and immunohistochemistry were used to analyze RNF7 expression level and its correlation with immune cell infiltration in non-small cell lung cancer. The impact of RNF7 expression levels on prognosis of lung cancer patients was analyzed using Kaplan-Meier survival analysis. CMT-167 cells with RNF7 overexpression or knockdown were inoculated subcutaneously in C57BL/6 mice, and the mice in RNF7 knockdown group were treated with anti-PD-1 or IgG isotype control 7 days after the inoculation. The tumor tissues were harvested after 30 days for tumor volume measurement, detection of S100A8+A9 and Gr-1 expressions with immunohistochemistry, and analysis of MDSC infiltration. Gene set enrichment analysis (GSEA) was performed to identify the potential pathways regulated by RNF7 in NSCLC. Western blotting and luciferase assays were used to assess the impact of RNF7 on the NF-κB signaling pathway. ELISA and RT-qPCR were used to measure chemokine (C-X-C motif) ligand 1 (CXCL1) expression.

RESULTS:

RNF7 expression was significantly upregulated in NSCLC, and high RNF7 expression levels were associated with poor prognosis of the patients (P < 0.001). TIMER2.0 analysis revealed a positive correlation between RNF7 expression and MDSC infiltration (P < 0.001). GSEA suggested that RNF7 was enriched in the NF-κB signaling pathway. In NSCLC cells, RNF7 knockdown significantly inhibited NF-κB activation and reduced CXCL1 expression. In the tumor-bearing mice, RNF7 overexpression significantly increased MDSC infiltration in the tumor tissue, and RNF7 knockdown obviously reduced MDSC infiltration and enhanced the efficacy of anti-PD-1 therapy.

CONCLUSION:

High expression of RNF7 in NSCLC cells promotes CXCL1 expression by activating the NF-κB signaling pathway, thus leading to the chemotactic recruitment of MDSCs, which contributes to tumor resistance to antiPD-1 therapy.

2020-12-01·Journal of hematology & oncology1区 · 医学

CDK7 inhibitor THZ1 enhances antiPD-1 therapy efficacy via the p38α/MYC/PD-L1 signaling in non-small cell lung cancer

1区 · 医学

ArticleOA

作者: Dong, Xiaorong ; Wu, Gang ; Chen, Yaobing ; Zhou, Xiaoshu ; Xu, Shuangbing ; Zhang, Tao ; Meng, Rui ; Liu, Li ; Hong, Jiaxin ; Zhang, Sheng ; Zhang, Ruiguang ; Wang, Jian ; Tang, Jing ; Lin, Zhenyu ; Zong, Yan ; Yang, Kunyu ; Xu, Yingzhuo

Abstract:

Background:

The cyclin-dependent kinase 7 (CDK7) subunit of TFIIH regulates RNA polymerase-II-based transcription and promotes tumor progression. However, the mechanisms involved in CDK7-mediated immune evasion are unclear in non-small cell lung cancer (NSCLC).

Methods:

RNA silencing and pharmacologic inhibitors were used to evaluate the functions of CDK7/p38α/MYC/PD-L1 axis in cancer cell proliferation and antiPD-1 therapy resistance. Flow cytometry was performed to detect the status of the immune microenvironment after CDK7 inhibition and antiPD-1 therapy in vivo. CD8 depletion antibodies were used to assess the role of CD8+ T cells in combined CDK7 and PD-1 blockade. The associations among CDK7, p38α, MYC, PD-L1, infiltrating T cells, and survival outcomes were validated in two tissue microarrays and public transcriptomic data of NSCLC.

Results:

High CDK7 mRNA and protein levels were identified to be associated with poor prognosis in NSCLC. CDK7 silencing and CDK7 inhibitor THZ1 elicited apoptosis and suppressed tumor growth. Moreover, CDK7 ablation specifically suppressed p38α/MYC-associated genes, and THZ1 inhibited MYC transcriptional activity through downregulating p38α. CDK7 inhibition sensitized NSCLC to p38α inhibitor. Further, THZ1 suppressed PD-L1 expression by inhibiting MYC activity. THZ1 boosted antitumor immunity by recruiting infiltrating CD8+ T cells and synergized with antiPD-1 therapy. The CDK7/MYC/PD-L1 signature and infiltrating T cell status collectively stratified NSCLC patients into different risk groups.

Conclusion:

These data suggest that the combined CDK7 inhibitor THZ1 and antiPD-1 therapy can be an effective treatment in NSCLC.

2019-05-19·mAbs2区 · 医学

Sym021, a promising anti-PD1 clinical candidate antibody derived from a new chicken antibody discovery platform

2区 · 医学

Article

作者: Bouquin, Thomas ; Uhlenbrock, Franziska ; Pedersen, Mikkel W ; Lindsted, Trine ; Kragh, Michael ; Gad, Monika ; Horak, Ivan D ; Fröhlich, Camilla ; Galler, Gunther R ; Dietrich, Nikolaj ; Gjetting, Torben ; Melander, Maria C ; Grandal, Michael M ; Koefoed, Klaus ; Lantto, Johan ; Bhatia, Vikram K ; Strandh, Magnus

Discovery of therapeutic antibodies is a field of intense development, where immunization of rodents remains a major source of antibody candidates. However, high orthologue protein sequence homology between human and rodent species disfavors generation of antibodies against functionally conserved binding epitopes. Chickens are phylogenetically distant from mammals. Since chickens generate antibodies from a restricted set of germline genes, the possibility of adapting the Symplex antibody discovery platform to chicken immunoglobulin genes and combining it with high-throughput humanization of antibody frameworks by "mass complementarity-determining region grafting" was explored. Hence, wild type chickens were immunized with an immune checkpoint inhibitor programmed cell death 1 (PD1) antigen, and a repertoire of 144 antibodies was generated. The PD1 antibody repertoire was successfully humanized, and we found that most humanized antibodies retained affinity largely similar to that of the parental chicken antibodies. The lead antibody Sym021 blocked PD-L1 and PD-L2 ligand binding, resulting in elevated T-cell cytokine production in vitro. Detailed epitope mapping showed that the epitope recognized by Sym021 was unique compared to the clinically approved PD1 antibodies pembrolizumab and nivolumab. Moreover, Sym021 bound human PD1 with a stronger affinity (30 pM) compared to nivolumab and pembrolizumab, while also cross-reacting with cynomolgus and mouse PD1. This enabled direct testing of Sym021 in the syngeneic mouse in vivo cancer models and evaluation of preclinical toxicology in cynomolgus monkeys. Preclinical in vivo evaluation in various murine and human tumor models demonstrated a pronounced anti-tumor effect of Sym021, supporting its current evaluation in a Phase 1 clinical trial. Abbreviations: ADCC, antibody-dependent cellular cytotoxicity; CD, cluster of differentiation; CDC, complement-dependent cytotoxicity; CDR, complementarity determining region; DC, dendritic cell; ELISA, enzyme-linked immunosorbent assay; FACS, fluorescence activated cell sorting; FR, framework region; GM-CSF, granulocyte-macrophage colony-stimulating factor; HRP, horseradish peroxidase; IgG, immunoglobulin G; IL, interleukin; IFN, interferon; mAb, monoclonal antibody; MLR, mixed lymphocyte reaction; NK, natural killer; PBMC, peripheral blood mono-nuclear cell; PD1, programmed cell death 1; PDL1, programmed cell death ligand 1; RT-PCR, reverse transcription polymerase chain reaction; SEB, Staphylococcus Enterotoxin B; SPR, surface Plasmon Resonance; VL, variable part of light chain; VH, variable part of heavy chain.

项与 Sym-021 相关的新闻（医药）

2025-07-22

·PipelineReview

OncoC4 Doses First Patient with Potential Best-in-Class PD-1/VEGF Bispecific Antibody AI-081 in Phase 2 Portion of BIPAVE-001 Trial for Advanced Solid Tumors in US

Excellent safety observed across initial dose escalation with objective response at the lowest dose tested (1 mg/kg of AI-081) ROCKVILLE, MD, USA I July 22, 2025 I OncoC4, Inc., a late-stage biopharmaceutical company developing novel medicines for cancer today announced the first patient has been dosed in the Phase 2 portion of the Phase 1/2 BIPAVE-001 trial (NCT06635785) evaluating AI-081, a potentially best-in-class PD-1 and VEGF bispecific antibody. “We are encouraged by the excellent safety, favorable pharmacokinetics and promising efficacy seen across the initial dose escalation of AI-081. Importantly, objective anti-tumor response was observed at the lowest dose tested, which is lower than other VEGF and PD-1/PD-L1 bispecific therapies in clinical development,” said Pan Zheng, MD, PhD, Co-Founder and Chief Medical Officer. “This early clinical signal is consistent with AI-081’s best-in-class potential demonstrated by data from multiple preclinical cancer models. We look forward to further dose optimization in the Phase 2 trial with initial focus in non-small cell lung cancer (NSCLC).” The BIPAVE-001 Phase 1/2 trial is designed to evaluate the safety, pharmacokinetic, and efficacy of AI-081 in two integrated parts. Part A is an ongoing, first-in-human Phase 1 dose escalation and dose expansion study in patients with advanced solid tumors. Part B, the Phase 2 portion, includes dose optimization trials comparing the safety and clinical activities of AI-081 either as monotherapy or in combination therapy with standard of care in selected indications. The study is being carried out in the United States with 11 clinical sites actively enrolling patients. The Chinese regulatory agency also cleared the study. About AI-081 AI-081 is a PD-1 and VEGF bispecific antibody with best-in-class potential for the treatment of advanced solid tumors. Combining two proprietary and clinical-stage high-affinity anti-PD1 (AI-025) and anti-VEGF (AI-011) antibodies, AI-081 employs a tested and clinically proven head-and-tail bispecific configuration. Designed for strong cooperative interactions, AI-081 uses additional Fc silencing mutations to preserve immune effector cells. In molecular, cellular, and in vivo preclinical studies used to support the investigational new drug (IND) application, AI-081 demonstrated higher affinity for both targets, more effective cooperation between pathways, and enhanced in vivo activities over drug candidates in the same class. These findings highlight the high affinity and cooperative interactions of AI-081 have potential to deliver powerful, dual-targeted immune responses by enhancing PD-1 blockade in the presence of VEGF. About OncoC4 Based in Rockville, Maryland, OncoC4 is a privately held, late-stage biopharmaceutical company that is actively engaged in the discovery and development of novel biologicals for the treatment of cancer and immunological diseases. OncoC4’s pipeline features assets with first-in-class and best-in-class potential targeting both novel and well validated targets across oncology and immunological diseases. Among them, AI-081 is a fully owned and potentially best-in-class bispecific antibody candidate targeting PD-1 and VEGF. AI-081 is currently enrolling patients in a Phase1/2 trial that could enable two or more pivotal studies. In addition, OncoC4 has a strategic collaboration with BioNTech to co-develop gotistobart (BNT316/ONC-392), a next-generation anti-CTLA-4 antibody candidate, in multiple solid tumor indications, including an ongoing pivotal clinical trial in squamous non-small cell lung cancer. For more information, please visit www.oncoc4.com . SOURCE: OncoC4

临床1期临床申请临床2期

2025-07-09

·ioncology

EGFR突变非小细胞肺癌靶向治疗耐药后迎来转机！免疫联合化疗实现病理完全缓解，微环境分析揭示关键机制

点击蓝字关注我们导语：EGFR敏感突变型非小细胞肺癌（NSCLC）患者一旦靶向治疗失败，后续治疗选择极为有限。然而，广州医科大学附属第一医院何建行、梁文华教授及刘桑田医生近期发表的一例74岁女性患者的治疗经历为这一困境带来新希望——在多次EGFR-TKI耐药后，通过Pembrolizumab（帕博利珠单抗）联合化疗，患者不仅实现显著肿瘤退缩，术后病理评估更显示完全缓解（pCR），未见存活肿瘤细胞！长期生存随访显示无进展生存时间（PFS）超40个月。本文详解该病例的治疗历程与肿瘤微环境特征，为临床提供重要启示。一、病例速读患者资料74岁女性，无吸烟史，初诊为cT4N2M1a -IVA期EGFR L858R突变肺腺癌（伴肺内转移、胸膜及纵隔淋巴结受累）。治疗经过既往接受多线靶向治疗（一线：埃克替尼联合培美曲塞+奈达铂，PFS1:6.5个月，最佳疗效PR；二线：阿美替尼+安罗替尼序贯奥希替尼+贝伐珠单抗，PFS2：4.5个月，最佳疗效SD；），均出现疾病进展。（图1、图2）图1. 治疗时间轴关键治疗转折三代TKI耐药后启动免疫联合化疗方案：帕博利珠单抗+培美曲塞+卡铂，治疗2周期后评估疗效PR，4周期后行PET-CT检查示肿瘤代谢显著降低。随后该患者接受了“右肺上叶切除术”，术后病理显示肿瘤床95%为纤维化及炎症，5%为坏死组织，未见存活癌细胞，证实为病理完全缓解（pCR）。术后患者接受免疫维持治疗，随访40个月无复发。（图1、图2）图2. 靶病灶影像学疗效评估红色箭头表示主要靶病灶，蓝色箭头表示次要靶病灶，黄色箭头表示转移淋巴结。A，EGFR-TKI治疗期间肿瘤影像学改变；B，免疫联合化疗期间肿瘤影像学改变；C，PET-CT评估免疫联合化疗前后肿瘤代谢水平。二、机制揭秘肿瘤微环境分析：通过多重免疫荧光技术对比免疫治疗前后肿瘤微环境（图3），发现以下关键特征：1.肿瘤PD-L1表达：靶向治疗耐药后，肿瘤细胞PD-L1阳性率超50%，提示潜在免疫治疗响应可能。（图4C）2.瘤内免疫细胞浸润：靶向治疗耐药后，肿瘤区域内显著富集PD-1+ CD8+ T细胞和PD-L1+巨噬细胞，提示存在功能被抑制的免疫微环境，该特征可能被PD-1/PD-L1抑制剂逆转。（图4D）3.免疫联合化疗激活免疫反应：手术切除标本中，CD45+免疫细胞、CD8+ T细胞及未成熟三级淋巴结构（TLS）显著增加，微环境转为免疫激活状态。（图3D-E）图3. 苏木精-伊红染色（HE）及多重免疫荧光（mIF）染色A-C，靶向治疗耐药后肿瘤组织的HE与mIF染色；D-E，手术切除样本的HE与mIF染色。mIF标记物包括DAPI（蓝色）、pan-CK（白色）、PD-L1（绿色）、CD45（红色）、CD68（黄色）、CD8（亮蓝色）及PD-1（橙色）。图4. 靶向治疗耐药后肿瘤与基质区域的统计分析A，肿瘤与基质区域的细胞组成；B，CD45+免疫细胞、CD8+ T细胞及CD68+巨噬细胞在肿瘤与基质区域的密度；C，肿瘤细胞PD-L1表达水平；D，肿瘤与基质区域中PD-1+CD8+ T细胞及PD-L1+ CD68+巨噬细胞的比例。三、临床启示与讨论传统观点认为，携带EGFR敏感突变的非小细胞肺癌（NSCLC）属于对免疫治疗反应较差的"冷肿瘤"。然而，本研究通过典型病例证实：在靶向治疗耐药后，特定亚组患者仍可能通过免疫联合治疗获得显著疗效。我们前期研究发现，EGFR-TKI治疗后快速进展（即PFS＜10个月）的患者，其后续免疫治疗有效率显著提升。这一现象可能由三重机制共同驱动：1）免疫特征：快速耐药人群的肿瘤组织呈现更高PD-L1阳性率、更密集的CD8+ T细胞浸润以及更高比例M1型巨噬细胞浸润；2）基因组特征：部分患者伴随较高肿瘤突变负荷（TMB，反映肿瘤新生抗原数量的指标），可能增强免疫系统识别能力；3）化疗协同效应：化疗药物通过诱导肿瘤细胞免疫原性死亡释放抗原，同时重塑微环境，为PD-1/PD-L1抑制剂创造更有利的作用条件。本病例中，患者耐药后肿瘤组织呈现以下特征：肿瘤细胞PD-L1高表达（TPS≥50%）、瘤内富集大量PD-1+CD8+ T细胞（处于激活状态的杀伤性免疫细胞）与PD-L1+巨噬细胞，这些特征可能与患者接受"化疗+免疫"联合方案后取得病理性完全缓解以及超过40个月的PFS密切相关。四、未来展望尽管免疫治疗在EGFR突变人群中的疗效仍需大规模研究加以验证，但这一成功案例为临床实践注入信心。如何精准筛选适应的患者、制定个体化的治疗方案是未来研究的重点和难点。在后续的探索中，我们可以通过对EGFR-TKI耐药患者常规进行再活检，基于多维度检测（包括PD-L1、TILs、TMB等）绘制个体化免疫微环境图谱；开发整合临床特征（如TKI-PFS）与分子标志物的预测模型，筛选最可能从免疫治疗中获益的亚组；针对免疫微环境特征设计差异化联合方案（如化疗增敏、放疗增敏、双免疫检查点阻断等），突破现有疗效瓶颈。此外,TKI序贯免化治疗的组合方案也具有较大的前景。病例原文：Liu, Sangtian et al. “Pathological complete response and long-term survival by pembrolizumab based immunochemotherapy in epidermal growth factor receptor mutated non-small cell lung cancer post-tyrosine kinase inhibitor failure: a case report and tumor microenvironment analysis.” Translational lung cancer research vol. 14,3 (2025): 1032-1041.参考文献：(上下滑动可查看）[1]Dong ZY, Zhang JT, Liu SY, Su J, Zhang C, Xie Z, Zhou Q, Tu HY, Xu CR, Yan LX, Li YF, Zhong WZ, Wu YL. EGFR mutation correlates with uninflamed phenotype and weak immunogenicity, causing impaired response to PD-1 blockade in non-small cell lung cancer. Oncoimmunology. 2017 Jul 26;6(11):e1356145. doi: 10.1080/2162402X.2017.1356145. PMID: 29147605; PMCID: PMC5674946.[2]Liu, Sangtian et al. “Patients With Short PFS to EGFR-TKIs Predicted Better Response to Subsequent Anti-PD-1/PD-L1 Based Immunotherapy in EGFR Common Mutation NSCLC.” Frontiers in oncology vol. 11 639947. 11 Mar. 2021, doi:10.3389/fonc.2021.639947[3]Azuma, K et al. “Association of PD-L1 overexpression with activating EGFR mutations in surgically resected nonsmall-cell lung cancer.” Annals of oncology : official journal of the European Society for Medical Oncology vol. 25,10 (2014): 1935-1940. doi:10.1093/annonc/mdu242[4]Yang, Ching-Yao et al. “Association between programmed death-ligand 1 expression, immune microenvironments, and clinical outcomes in epidermal growth factor receptor mutant lung adenocarcinoma patients treated with tyrosine kinase inhibitors.” European journal of cancer (Oxford, England : 1990) vol. 124 (2020): 110-122. doi:10.1016/j.ejca.2019.10.019[5]Qiao, Meng et al. “Immune Checkpoint Inhibitors in EGFR-Mutated NSCLC: Dusk or Dawn?.” Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer vol. 16,8 (2021): 1267-1288. doi:10.1016/j.jtho.2021.04.003[6]Yoon, Byung Woo et al. “High PD-L1 Expression is Associated with Unfavorable Clinical Outcome in EGFR-Mutated Lung Adenocarcinomas Treated with Targeted Therapy.” OncoTargets and therapy vol. 13 8273-8285. 20 Aug. 2020, doi:10.2147/OTT.S271011声明：本研究获国家自然科学基金等支持，患者知情同意书已存档。本文仅供学术交流，具体治疗方案需结合患者实际情况。（审校：梁文华教授）（来源：《肿瘤瞭望》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

免疫疗法临床结果临床研究

2025-06-20

·今日头条

癌症疫苗联手放化疗、免疫细胞等“六脉神剑”，打响抗癌组合拳

临床数据表明，即便手术成功切除肿瘤，仍有部分患者会面临癌症复发，这通常与体内残留的微量癌细胞有关。而癌症疫苗正通过激活免疫系统对残留癌细胞的精准识别能力，为术后防复发提供了全新解决方案。术后联合使用癌症疫苗与放化疗等手段，可通过「杀伤残余癌细胞 + 建立免疫记忆」的双重机制，显著降低复发转移风险。但遗憾的是，很多患者并不清楚如何通过联合治疗实现「1+1＞2」的抗癌效果。下面全球肿瘤医生网小编就为大家全面盘点临床验证的联合治疗方案，让每一份抗癌努力都能收获更强大的力量。全面盘点可与癌症疫苗携手抗癌的六大疗法，突破单药极限，实现1+1＞2的抗癌突破（一）癌症疫苗联合CAR-T：卵巢癌、睾丸癌等 BNT211是一种靶向Claudin-6(CLDN6)的新一代CART细胞疗法，其联合治疗方案包含编码CLDN6的纳米颗粒mRNA疫苗CARVac。该疫苗可在抗原呈递细胞表面表达CLDN6，特异性刺激体内CAR-T细胞扩增。通过增强CAR-T细胞持久性与肿瘤杀伤力，实现「1+1＞2」的协同抗癌效应。 BNT211的首次人体试验，共入组了44例复发/难治性晚期CLDN6阳性实体瘤（包括卵巢癌、睾丸癌等）患者，平均接受过4种治疗方案。将其分为两组：即联合治疗组（接受低剂量CLDN6 CAR-T细胞+CARVac疫苗联合治疗）、CAR-T单药治疗组。结果显示：在38例可评估的患者中，总缓解率（ORR）为44.7%，疾病控制率（DCR）为73.7% 。其中 1例患者获得完全缓解（CR）。（二）癌症疫苗联合NK细胞疗法：卵巢癌《Cureus》曾报道了一个应用“WT1-DC疫苗+NK细胞疗法联合治疗，让卵巢癌显著缩小”的案例。该患者是一位IV期双侧卵巢癌、伴腹水及全身多处转移者。此前接受过化疗（紫杉醇+卡铂AUC5），但效果不佳，遂入组接受WT1-DC疫苗+NK细胞+纳武单抗联合治疗。结果显示：治疗后，癌胚抗原（CEA）及CA125显著下降。腹部CT显示，在NK细胞治疗第56天后，腹水明显减少，提示腹膜播散情况改善。PET-CT显示，原发性肿瘤明显缩小，肺转移灶及腹膜播散灶消失，肝转移灶缩小（详见下图）。 ▼该患者治疗前和治疗142天，PET-CT对比 ▲图源“Cureus”，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（三）癌症疫苗联合化疗：胰腺癌《癌症免疫治疗杂志》发表了一项“应用WT1肽脉冲成熟树突状细胞（DC）与多药化疗方案，联合治疗不可切除的胰腺导管腺癌（UR-PDAC）”的临床研究。该研究共纳入10例不可切除的胰腺导管腺癌（UR-PDAC）患者，入组接受多药化疗方案（白蛋白结合型紫杉醇+吉西他滨）+WT1-DC疫苗治疗。结果显示：有患者病灶均呈现退缩，降幅达0.0%~57.4% 。其中 7例（70%）达到部分缓解（PR），其余3例维持长期病情稳定（SD）。9例可评估患者中位无进展生存期（PFS）达2.23年，中位总生存期（OS）长达3.52年，远超传统化疗的1年生存期预期。以一位转移性胰腺导管腺癌（M-PDAC）患者（WT1-DC-05）为例，治疗前后的CE-CT与18F-FDGPET/CT对比明显（详见下图）。 ▲图源“BMJ”，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（四）癌症疫苗联合放疗——肠癌《Cureus》期刊报道了一则应用DC疫苗联合放疗治疗肠癌的震撼案例：该患者是一位40岁男性，确诊晚期小肠癌，伴主动脉旁淋巴结转移及腹膜播散，对传统化疗完全耐药，并出现胆管与十二指肠梗阻，只能依靠胆管支架及中心静脉营养维持生命。因腹部癌痛剧烈，患者先接受 8Gy 单次姑息性调强放疗（IMRT），但疼痛控制无效，体能状态（PS）评分仅 4 分，终日依赖轮椅活动。绝境中，患者入组WT1-DC联合放疗的创新治疗方案：在姑息性调强放疗（IMRT）放疗3周后，启动“α-Galcer-DC疫苗+纳武单抗+两次活化淋巴细胞”联合治疗，总疗程约 3 个月。结果显示：治疗前后3个月腹部CT显示，小肠癌病灶显著减少（详见下图）。此外，血液检查显示， CA19-9肿瘤标志物水平显著下降，胆红素降低，肝功能明显改善。腹痛完全缓解，恢复流质饮食，体能评分从4分跃升至2分，可独立步行至医院，并自主完成如厕、洗澡等日常活动。 ▲图源“Cureus”，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（五）癌症疫苗联合免疫检查点抑制剂（ICI）：胃癌 Neo-MoDC疫苗（载有新抗原的单核细胞衍生的树突状细胞疫苗）是我国自主研发的一款新型个性化癌症疫苗，能充分地调动机体的免疫系统，并促进T细胞富集，通过调动T细胞，对全身癌细胞进行猛烈攻击。《PrecisionOncology》报道过一个“Neo-MoDC疫苗+免疫检查点抑制剂（ICI）联合治疗”的代表性案例。这是一位IV期转移性胃癌（BormannIII型）患者，在经历FOLFOX化疗及D2根治性远端胃切除术后，病情仍持续进展，出现腹膜及淋巴结转移。由于无法耐受进一步化疗，患者入组接受Neo-MoDC疫苗+ICI联合治疗。结果显示：治疗2周后，患者恶性腹水完全消失；血清CA-125指标从治疗前的596U/ml骤降至64U/ml，标志着肿瘤活性得到迅速抑制，病情快速趋于稳定。初次接种疫苗后第231天，PET检查显示右侧卵巢转移灶近乎完全消退；联合治疗第389天，CT复查证实卵巢种植转移灶彻底消失（详见下图），达到影像学完全缓解（CR）。截至数据统计时，患者病灶完全消退状态已持续25个月，远超晚期胃癌患者12-16个月的中位生存期，打破了传统治疗的生存极限。 ▲图源“npj”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除癌症疫苗联合PD-1抑制剂：肺癌《细胞研究》曾报道一则突破性临床案例：一位69岁男性患者在年度体检中发现肺结节，经CT及PET-CT检查显示双肺与纵隔淋巴结存在多发高代谢病灶，病理活检确诊为晚期非小细胞肺癌（NSCLC），已失去手术机会。患者入组接受“KRASG12VmRNA疫苗+帕博利珠单抗”联合治疗方案。结果显示：治疗3个周期后，右肺病灶基本消失，左肺病灶及纵隔淋巴结显著退缩（详见下图）。按RECIST1.1标准，该患者达到部分缓解（PR）。 ▲图源“Cell Research”，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（六）癌症疫苗联合新抗原T细胞疗法：肝癌《癌症免疫学研究》发表的II期临床研究（NCT03067493）首次探索了“个性化新抗原DC疫苗联合新抗原激活T细胞”疗法在肝癌术后防复发中的价值。研究纳入10例接受根治性手术或射频消融（RFA）的肝细胞癌（HCC）患者，术后接受DC疫苗+个体化新抗原免疫细胞联合治疗。结果显示：50%（5例）患者在治愈性治疗后2年未出现肿瘤复发（详见下图A），中位无复发生存期（DFS）达18.3个月（95%CI：4.9-NA），较传统术后治疗显著延长。此外，免疫应答与生存强关联：有免疫应答患者的DFS显著长于无应答者（P=0.012），其中71.4%免疫应答者在2年内保持无复发，而无免疫应答患者均复发。 ▲图源“Cancer Immunol Res”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除小编寄语癌症疫苗经历几十载的发展，逐渐从基础研究阶段，转向了临床研究阶段，一次次突破技术壁垒，扩大应用范围，企图唤醒免疫系统，重新识别并杀伤癌细胞；同时产生免疫记忆反应，使免疫细胞发挥持久的保护作用。尤其考虑到最近的进展，癌症疫苗正迅速成为实体瘤治疗的潜力股！但需要提醒大家的是，癌症作为一种高度复杂且突变频繁的疾病，仅依靠单一治疗手段，很难达到理想的治疗效果。目前，较为理想的治疗策略是在权威医院进行手术、放化疗等传统治疗的基础上，综合考虑患者的病情严重程度、个体体质差异、突变靶点特征以及经济状况等多方面因素，合理辅助靶向药物、免疫细胞治疗（如CAR-T、TCR-T、TIL细胞疗法、DC疫苗等）、质子治疗、电场疗法等新型治疗手段。通过这种多管齐下的治疗方式，能够巩固传统治疗的效果，降低肿瘤复发风险，提高患者的生存质量，并有效延长生存期。参考资料 [1]Nagai H,et al.Late-Stage Ovarian Cancer With Systemic Multiple Metastases Shows Marked Shrinkage Using a Combination of Wilms' Tumor Antigen 1 (WT1) Dendritic Cell Vaccine, Natural Killer (NK) Cell Therapy, and Nivolumab. Cureus. 2024 Mar 22;16(3):e56685. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10960621/ [2]Koido S, Taguchi J, Shimabuku M, et al. Dendritic cells pulsed with multifunctional Wilms’ tumor 1 (WT1) peptides combined with multiagent chemotherapy modulate the tumor microenvironment and enable conversion surgery in pancreatic cancer[J]. Journal for Immunotherapy of Cancer, 2024, 12(10): e009765. https://jitc.bmj.com/content/12/10/e009765 [3]Nagai H,et al.Combination of Radiation Therapy, Wim's Tumor 1 (WT1) Dendritic Cell Vaccine Therapy, and α-Galactosylceramide-Pulsed Dendritic Cell Vaccine Therapy for End-Stage Small Bowel Cancer. Cureus. 2024 Jul 20;16(7):e64972. doi: 10.7759/cureus.64972. Erratum in: Cureus. 2025 May 5;17(5):c220. https://pmc.ncbi.nlm.nih.gov/articles/PMC11259906/ [4]Guo Z,et al.Durable complete response to neoantigen-loaded dendritic-cell vaccine following anti-PD-1 therapy in metastatic gastric cancer. NPJ Precis Oncol.2022 Jun 3;6(1):34. https://www.nature.com/articles/s41698-022-00279-3 [5]Wang X,et al.Combination therapy of KRAS G12V mRNA vaccine and pembrolizumab: clinical benefit in patients with advanced solid tumors[J]. Cell Research, 2024, 34(9): 661-664. https://www.nature.com/articles/s41422-024-00990-9 [6]Peng S,et al.Combination neoantigen-based dendritic cell vaccination and adoptive T-cell transfer induces antitumor responses against recurrence of hepatocellular carcinoma[J]. Cancer immunology research, 2022, 10(6): 728-744. https://aacrjournals.org/cancerimmunolres/article/10/6/728/699035/Combination-Neoantigen-Based-Dendritic-Cell 本文为全球肿瘤医生网原创，未经授权严禁转载

100 项与 Sym-021 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
晚期恶性实体瘤	临床1期	美国	Adir SRL	2021-10-15
晚期恶性实体瘤	临床1期	加拿大	Adir SRL	2021-10-15
胆管癌	临床1期	美国	Symphogen A/S	2020-10-12
胆管癌	临床1期	加拿大	Symphogen A/S	2020-10-12
胆管癌	临床1期	法国	Symphogen A/S	2020-10-12
胆管癌	临床1期	西班牙	Symphogen A/S	2020-10-12
Vater壶腹癌	临床1期	美国	Symphogen A/S	2020-10-12
Vater壶腹癌	临床1期	加拿大	Symphogen A/S	2020-10-12
Vater壶腹癌	临床1期	法国	Symphogen A/S	2020-10-12
Vater壶腹癌	临床1期	西班牙	Symphogen A/S	2020-10-12

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适应症

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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


ASCO2024	N/A	复发性头颈部鳞状细胞癌 PD-L1 positive (CPS≥1)	89	anti-PD-1 (irAEs)	顧構糧選積蓋簾壓獵積(醖膚鏇憲願糧蓋範積窪) = 10% 積願壓簾構窪鏇窪簾鹹 (鹽餘廠醖襯襯築積膚鹽 ) 更多	积极	2024-05-24
				anti-PD-1 (non-irAEs)
ASCO2023	N/A	黑色素瘤	86	Anti-PD-1 antibody plus ipilimumab therapy	襯願鏇壓憲醖構觸淵糧(簾繭遞選築衊簾簾廠築) = 艱鑰憲顧鹹鹹願膚壓構選糧憲糧窪憲糧積鏇繭 (範艱築憲鹹淵襯艱積築 ) 更多	积极	2023-05-31
NCT03489343 \| NCT03311412 \| NCT03489369 (ESMO2020)	临床1期	肿瘤转移 \| 晚期恶性实体瘤 \| 淋巴瘤	-	Sym021	艱簾構齋襯遞繭繭淵簾(網夢鬱獵獵遞觸餘夢壓) = Sym021, Sym022 and Sym023 alone and Sym021 in combination with either Sym022 or Sym023 were well tolerated with AE profiles typical of immune checkpoint inhibitors 鑰築廠簾積膚膚鏇鬱積 (範遞糧築廠鹹齋鑰獵齋 )	-	2020-09-20
				Sym022
AUA2020	N/A	泌尿生殖系统肿瘤 HLA-I genotypes \| HLA-C genotypes \| KIR ligands ... 更多	51	anti-PD-1 drugs (HLA-A2 supertype)	觸獵齋衊糧構醖遞鹹範(願獵淵獵網繭膚膚顧繭) = 構獵醖選廠衊鏇製壓窪觸築襯顧窪淵築膚醖憲 (廠糧壓獵鬱顧網鹹膚鹹 )	-	2020-04-01
				anti-PD-1 drugs (Patients without HLA-A2 supertype)	觸獵齋衊糧構醖遞鹹範(願獵淵獵網繭膚膚顧繭) = 觸襯鏇獵鏇選膚夢膚壓觸築襯顧窪淵築膚醖憲 (廠糧壓獵鬱顧網鹹膚鹹 )
ASCO2017	N/A	转移性黑色素瘤	-	aPD1	顧壓醖餘艱選範憲襯襯(糧範衊鏇鹽鏇範齋壓願) = 遞鹽積鏇築膚襯餘獵鹽衊糧夢壓餘構鑰齋製夢 (網築繭觸構築淵積壓餘 ) 更多	-	2017-05-30
				aPD1 + IPI	廠範簾蓋簾製餘窪獵積(觸壓繭衊醖醖壓廠窪醖) = 鑰範獵膚膚餘築膚獵遞選醖製憲簾網齋淵窪夢 (鏇淵構獵簾遞艱廠積遞 ) 更多
ASCO2017	N/A	转移性黑色素瘤	64	aPD1 + aCTLA4	範襯窪製膚鏇遞顧獵願(顧廠廠壓醖壓積鬱製糧) = One death from irAEs occurred related to Toxic Epidermal Necrolysis (TEN) 觸觸壓衊膚鑰網醖繭艱 (願壓膚積鏇獵築簾膚製 ) 更多	积极	2017-05-30