留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

放射性药物联合免疫检查点抑制剂协同抗肿瘤研究新进展

曾馨莹 文雪君 郭志德 张现忠

曾馨莹, 文雪君, 郭志德, 张现忠. 放射性药物联合免疫检查点抑制剂协同抗肿瘤研究新进展[J]. 协和医学杂志, 2023, 14(4): 680-690. doi: 10.12290/xhyxzz.2023-0159
引用本文: 曾馨莹, 文雪君, 郭志德, 张现忠. 放射性药物联合免疫检查点抑制剂协同抗肿瘤研究新进展[J]. 协和医学杂志, 2023, 14(4): 680-690. doi: 10.12290/xhyxzz.2023-0159
ZENG Xinying, WEN Xuejun, GUO Zhide, ZHANG Xianzhong. Advances in Synergistic Antitumor Effects of Radiopharmaceuticals Combined with Immune Checkpoint Inhibitors[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(4): 680-690. doi: 10.12290/xhyxzz.2023-0159
Citation: ZENG Xinying, WEN Xuejun, GUO Zhide, ZHANG Xianzhong. Advances in Synergistic Antitumor Effects of Radiopharmaceuticals Combined with Immune Checkpoint Inhibitors[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(4): 680-690. doi: 10.12290/xhyxzz.2023-0159

放射性药物联合免疫检查点抑制剂协同抗肿瘤研究新进展

doi: 10.12290/xhyxzz.2023-0159
基金项目: 

国家自然科学基金 81901805

国家自然科学基金 21976150

国家自然科学基金 21906135

中央高水平医院临床科研专项 2022-PUMCH-B-071

中央高水平医院临床科研专项 2023-PUMCH-E-007

详细信息
    通讯作者:

    郭志德, E-mail: gzd666888@xmu.edu.cn

    张现忠, E-mail: zhangxzh@hotmail.com

  • 中图分类号: R45;R73

Advances in Synergistic Antitumor Effects of Radiopharmaceuticals Combined with Immune Checkpoint Inhibitors

Funds: 

National Natural Science Foundation of China 81901805

National Natural Science Foundation of China 21976150

National Natural Science Foundation of China 21906135

National High Level Hospital Clinical Research Funding 2022-PUMCH-B-071

National High Level Hospital Clinical Research Funding 2023-PUMCH-E-007

More Information
  • 摘要: 靶向放射性核素治疗诱导DNA双链断裂,激活cGAS-STING通路、NF-κB/IRF3通路和STAT1/3-IRF1通路,上调程序性死亡受体配体1(programmed death-ligand 1,PD-L1)的表达,促炎细胞因子、CD8+ T细胞及CD4+ T细胞在肿瘤中浸润增加,为免疫检查点抑制剂治疗提供了有利的免疫原性微环境。联合治疗使得正向调节免疫反应的记忆效应T细胞、M1型巨噬细胞及树突状细胞浸润增加,免疫抑制性的调节性T细胞、M2型巨噬细胞及髓源性抑制细胞下调,部分小鼠肿瘤完全缓解并产生免疫记忆。值得注意的是,放射性诊断药物2-[18F]FDG联合PD-L1抗体治疗也可调控免疫微环境,显著提高疗效。本文主要综述目前典型的放射性药物联合免疫检查点抑制剂协同抗肿瘤治疗策略,并强调联合治疗时间窗以及不同的治疗组合可能改善治疗效果,提出诊断放射性药物联合免疫治疗有望成为一种新的肿瘤治疗范式,或将成为未来研究的重要方向。
    作者贡献:曾馨莹、文雪君负责文献检索、论文撰写及修订;郭志德、张现忠负责论文选题和审校。
    利益冲突:所有作者均声明不存在利益冲突
  • 图  1  2-[18F]FDG联合PD-L1 ICI治疗可显著延缓肿瘤生长,提高荷瘤小鼠总生存期

    A.MC38荷瘤小鼠的治疗程序和时间表示意图;B.不同治疗组MC38荷瘤小鼠的个体肿瘤生长情况以及90 d存活率(αP指PD-L1抗体剂量为10 mg/kg,αP##指PD-L1抗体剂量为20 mg/kg;18F-F指2-[18F]FDG剂量为925 MBq/kg,18F-F##指2-[18F]FDG剂量为1850 MBq/kg;@4 h指PD-L1抗体与2-[18F]FDG的给药时间窗为4 h);C.2-[18F]FDG诱导MC38荷瘤小鼠免疫治疗的时间依赖性肿瘤生长曲线和生存曲线;D.ELISA法检测血液中细胞因子IFN-γ、TNF-α、IL-6水平的动态变化;E.记忆性T细胞浸润的流式细胞术分析(CD4+CD44highCD62Llow和CD8+CD44highCD62Llow);F.用FlowJo v10软件定量分析脾脏总细胞中CD4+CD44highCD62Llow细胞和CD8+CD44highCD62Llow细胞比例;G.治愈小鼠的左后侧在第91天再次接种MC38细胞,并监测至第150天;H.2-[18F]FDG联合PD-L1单抗可增强持久免疫记忆
    PD-L1:程序性死亡受体配体1;IFN:干扰素;TNF:肿瘤坏死因子;IL:白细胞介素;*P<0.05;**P<0.01;***P<0.001;****P<0.0001

    图  2  2-[18F]FDG诱导的PD-L1上调通过NF-κB/IRF3途径介导

    A.MC38细胞与2-[18F]FDG共孵育不同时间后的细胞活力检测;B.用2-[18F]FDG (3.7 MBq) 照射MC38细胞24 h,用γH2AX和EdU染色检测DNA DSB和DNA修复水平;C、D.2-[18F]FDG激活NF-κB和IRF3信号通路的验证[56]
    PD-L1:同图 1

    图  3  2-[18F]FDG诱导的PD-L1上调与经典STAT1/3-IRF1通路相关

    A.与2-[18F]FDG共孵育24 h后肿瘤细胞中DEGs的热图;B.2-[18F]FDG激活STAT1/3和IRF1信号通路与PD-L1上调相关[56]
    PD-L1:同图 1

    表  1  近5年发表的放射性药物联合ICI治疗的临床前研究

    第一作者 放射性药物 射线类型 ICI 肿瘤类型 给药方案 TIME变化 治疗效果
    Wen[56] 2-[18F] β/γ anti-PD-L1 MC38
    CT26
    2-[18F]FDG(37 MBq)给药后4 h静脉注射anti-PD-L1 (400 μg),共2个疗程(d0, d4) PD-L1、CD8+、CD4+ T细胞上调,DCs、M1巨噬细胞上调,促炎细胞因子上调,Tregs、MDSC下调 抑制肿瘤生长,延长生存期,产生免疫记忆
    文雪君[57] 99mTc-RGD γ anti-PD-L1 MC38 99mTc-RGD(18.5或37 MBq)给药后4 h静脉注射anti-PD-L1(400 μg),共2个疗程(d0, d4) PD-L1上调 完全缓解率为75%,90 d内无复发
    Wen[32] 64Cu-DOTA-EB-cRGDfK β anti-PD-L1 MC38 TRT(18.5 MBq)后4 h静脉注射anti-PD-L1(200 μg) PD-L1上调,CD8+及CD4+ T细胞上调,Tregs下调,促炎细胞因子上调 完全缓解率为100%, 生存率为100%, 产生免疫记忆
    Wen[31] 177Lu-DOTA-EB-cRGDfK β anti-PD-L1 MC38
    CT26
    TRT(9.25 MBq)后4 h静脉注射anti-PD-L1(200 μg) PD-L1上调,CD8+及CD4+T细胞上调,Tregs下调,促炎细胞因子上调 完全缓解率为100%, 生存率为100%, 产生免疫记忆
    Wen[58] 131I-αPD-L1 β anti-PD-L1 MC38
    CT26
    TRT(11.1 MBq)与anti-PD-L1(200 μg)同时静脉注射给药 PD-L1上调 延长生存期
    Choi[36] 177Lu-LLP2A β anti-CTLA-4+anti-PD-1/PD-L1 B16F10 TRT(30 MBq)在d0给药,ICI(各200 μg)在d1、d4、d7腹腔注射给药 - 显著提高生存率
    Guzik[33] 177Lu-DOTA-folate β anti-CTLA-4 NF9006 TRT(5 MBq)在d0给药,anti-CTLA-4(200 μg)在d1、d4、d7腹腔注射给药 - 抑制肿瘤生长,延长中位生存期
    Ren[34] 177Lu-DOTA-Y003 β anti-PD-L1 MC38 TRT(3.7 MBq)在d0、d8给药,anti-PD-L1(100 μg)在d2、d4、d6、d10、d12、d14腹腔注射给药 PD-L1上调,CD8+及CD4+ T细胞上调 抑制肿瘤生长,生存率为100%
    Czernin[39] 225Ac-PSMA-617 α anti-PD-1 RM1-PGLS TRT(30 kBq)在d0给药,anti-PD-1(200 μg)在d1、d4、d8、d11腹腔注射给药 - 抑制肿瘤生长,25%完全缓解
    Vito[37] 177Lu-DNP-DOTA-BSA β anti-CTLA-4+anti-PD-L1 E0771 TRT(4.4 MBq)在d0、d4给药,ICI(各200 μg)从d2开始每3天腹腔给药1次,共10次 CD4+T细胞、巨噬细胞及MDSC下调 延长生存期
    Brown[22] 90Y-NM600 β anti-CTLA-4 LLC 在d0进行EBRT(12 Gy)以及TRT (1.85 MBq),anti-CTLA-4(200 μg)在d3、d6、d9腹腔给药 - 减少肿瘤转移,产生免疫记忆
    Rouanet[17] 131I-ICF01012 β anti-CTLA-4+anti-PD-1/PD-L1 B16F10 TRT(18.5 MBq)在d0给药,ICI(各200 μg)在d-4、d0、d4、d8腹腔给药 T细胞衰竭相关基因CD274,LAG3和Eomes增加 延长生存期
    Potluri[23] 90Y-NM600 β anti-PD-1 TRAMP-C1
    Myc-CaP
    TRT(9.25 MBq)在d0给药,anti-PD-1(200 μg)在d0、d3、d6腹腔给药 CD8+ T细胞、Tregs细胞上调,PD-L1上调 未提高疗效
    Chen[30] 177Lu-EB-RGD β anti-PD-L1 MC38 TRT(18.5 MBq)在d0给药,anti-PD-L1(200 μg)在d1、d4、d7腹腔给药 CD8+ T细胞浸润,PD-L1上调 抑制肿瘤生长,生存率为100%
    Li[47] 212Pb-VMT01 α anti-CTLA-4+anti-PD-1 B16F10 TRT(4.1 MBq)在d0给药,ICI(各200 μg)每周2次腹腔给药 CD3+、CD4+、CD8+淋巴细胞上调 43%完全缓解,延长生存期,产生免疫记忆
    Dabagian[41] 211At-MM4 α anti-PD-1 U87MG TRT(0.72 MBq)在d0给药,anti-PD-1(200 μg)在d-3、d0、d3腹腔给药 PD-L1上调,CD8+及CD4+ T细胞上调 完全缓解率为100%
    Lejeune[51] MSLN-TTC
    (227Th)
    α anti-PD-L1 MC38-hMSLN TRT(5 kBq)在d0给药,anti-PD-L1(30 μg)每周2次腹腔给药 CD8+T细胞上调,IFNγ、CCL3、CCL4、IL-2、IL-5和IL-10上调,TGF-β和FOXP3上调 58.3%完全缓解,延长生存期
    Malo[35] 177Lu-h8C3
    225Ac-h8C3
    β
    α
    anti-PD-1 Cloudman S91 177Lu(3.7 MBq)在d0、d7给药,anti-PD-1(250 μg)在d1、d4、d7腹腔给药 未观察到肿瘤T细胞浸润增加 177Lu抑制肿瘤生长,延长生存期,225Ac联合治疗无效
    Patel[19] 90Y-NM600 β anti-CTLA-4 + anti-PD-L1 B78
    NXS2
    4T1
    TRT(1.85 MBq)在d0给药,anti-CTLA-4(200 μg)在d3、d6、d9腹腔给药;EBRT (12 Gy)及TRT(1.85 MBq)在d0给药,anti-CTLA-4(200 μg)在d3、d6、d9腹腔给药 促炎细胞因子(IFN-γ, IL-10)的产生显著增加,效应T细胞浸润,联合中等剂量EBRT诱导远隔效应 显著抑制肿瘤生长,延长生存期,产生免疫记忆,原发及对侧肿瘤均缓解(46.7%完全缓解)
    Nosanchuk[48] 213Bi-8C3 α anti-CTLA-4 B16-F10 TRT(5.55 MBq),anti-CTLA-4(100 μg)在d1、d5、d7腹腔给药 - TRT及联合治疗均减少肺转移,但二者无差异
    Zhang[21] 131I- MnO2-BSA β anti-PD-L1 4T1 TRT(18.5 MBq)在d0给药,anti-PD-L1(20 μg)在d1、d3、d5腹腔给药 CTLs浸润增加,Tregs、F4/80+ TAM下调,PD-L1上调,TNF-α、IFN-γ上调 抑制原发性肿瘤和远处肿瘤生长
    Zhang[42] 211At-ATE-MnO2-BSA α anti-PD-L1 4T1
    CT26
    TRT(555 kBq)在d0给药,anti-PD-L1(75 μg)在d1、d3、d5腹腔给药 CTLs浸润增加,TNF-α、IFN-γ上调,Tregs无变化,TEM浸润增加,TCM减少 有效抑制原发性肿瘤和远处肿瘤的生长,产生了长期免疫记忆
    注:均以第一次TRT治疗为d0,d-3为TRT给药前3 d,d-4为TRT给药前4 d,所有TRT均是静脉注射给药,均估算小鼠体质量为20 g换算剂量;PD-1:程序性死亡[蛋白]-1;CTLA-4:细胞毒性T淋巴细胞抗原4;TRT:靶向放射性核素治疗;ICI:免疫检查点抑制剂;DCs:树突状细胞;Tregs:调节性T细胞;MDSC:髓源性抑制细胞;EBRT:外照射放疗;LAG3:淋巴细胞激活基因-3;CCL:趋化因子C-C-基元配体;TGF-β:转化生长因子-β;TEM:效应记忆T细胞;TCM:中央记忆T细胞;TAM:肿瘤相关巨噬细胞;CTLs:细胞毒性T淋巴细胞;FOXP3:叉头蛋白P3;Emoes:脱中胚蛋白;IFN、TNF、IL、PD-L1:同图 1
    下载: 导出CSV
  • [1] FDA approves anti-LAG3 checkpoint[J]. Nat Biotechnol, 2022, 40: 625.
    [2] Yi M, Zheng X, Niu M, et al. Combination strategies with PD-1/PD-L1 blockade: current advances and future directions[J]. Mol Cancer, 2022, 21: 28. doi:  10.1186/s12943-021-01489-2
    [3] de Miguel M, Calvo E. Clinical Challenges of Immune Checkpoint Inhibitors[J]. Cancer Cell, 2020, 38: 326-333. doi:  10.1016/j.ccell.2020.07.004
    [4] Fradet Y, Bellmunt J, Vaughn DJ, et al. Randomized phase Ⅲ KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of > 2 years of follow-up[J]. Ann Oncol, 2019, 30: 970-976. doi:  10.1093/annonc/mdz127
    [5] McLaughlin M, Patin EC, Pedersen M, et al. Inflammatory microenvironment remodelling by tumour cells after radiotherapy[J]. Nat Rev Cancer, 2020, 20: 203-217. doi:  10.1038/s41568-020-0246-1
    [6] Pouget JP, Lozza C, Deshayes E, et al. Introduction to radiobiology of targeted radionuclide therapy[J]. Front Med (Lausanne), 2015, 2: 12.
    [7] Deng L, Liang H, Xu M, et al. STING-Dependent Cytosolic DNA Sensing Promotes Radiation-Induced Type Ⅰ Interferon-Dependent Antitumor Immunity in Immunogenic Tumors[J]. Immunity, 2014, 41: 843-852. doi:  10.1016/j.immuni.2014.10.019
    [8] Zhang X, Zhang H, Zhang J, et al. The paradoxical role of radiation-induced cGAS-STING signalling network in tumour immunity[J]. Immunology, 2023, 168: 375-388. doi:  10.1111/imm.13592
    [9] Lan Y, Moustafa M, Knoll M, et al. Simultaneous targeting of TGF-beta/PD-L1 synergizes with radiotherapy by reprogramming the tumor microenvironment to overcome immune evasion[J]. Cancer Cell, 2021, 39: 1388-403. e10. doi:  10.1016/j.ccell.2021.08.008
    [10] Sha CM, Lehrer EJ, Hwang C, et al. Toxicity in combination immune checkpoint inhibitor and radiation therapy: A systematic review and meta-analysis[J]. Radiother Oncol, 2020, 151: 141-148. doi:  10.1016/j.radonc.2020.07.035
    [11] Procureur A, Simonaggio A, Bibault JE, et al. Enhance the Immune Checkpoint Inhibitors Efficacy with Radiotherapy Induced Immunogenic Cell Death: A Comprehensive Review and Latest Developments[J]. Cancers (Basel), 2021, 13: 678. doi:  10.3390/cancers13040678
    [12] Twyman-Saint Victor C, Rech AJ, Maity A, et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer[J]. Nature, 2015, 520: 373-377. doi:  10.1038/nature14292
    [13] Formenti SC, Demaria S. Systemic effects of local radiotherapy[J]. Lancet Oncol, 2009, 10: 718-726. doi:  10.1016/S1470-2045(09)70082-8
    [14] Formenti SC, Rudqvist NP, Golden E, et al. Radiotherapy induces responses of lung cancer to CTLA-4 blockade[J]. Nat Med, 2018, 24: 1845-1851. doi:  10.1038/s41591-018-0232-2
    [15] Kleinendorst SC, Oosterwijk E, Bussink J, et al. Combining Targeted Radionuclide Therapy and Immune Checkpoint Inhibition for Cancer Treatment[J]. Clin Cancer Res, 2022, 28: 3652-3657. doi:  10.1158/1078-0432.CCR-21-4332
    [16] Sun Q, Li J, Ding Z, et al. Radiopharmaceuticals heat anti-tumor immunity[J]. Theranostics, 2023, 13: 767-786. doi:  10.7150/thno.79806
    [17] Rouanet J, Benboubker V, Akil H, et al. Immune checkpoint inhibitors reverse tolerogenic mechanisms induced by melanoma targeted radionuclide therapy[J]. Cancer Immunol Immunother, 2020, 69: 2075-2088. doi:  10.1007/s00262-020-02606-8
    [18] Jagodinsky JC, Jin WJ, Bates AM, et al. Temporal analysis of type 1 interferon activation in tumor cells following external beam radiotherapy or targeted radionuclide therapy[J]. Theranostics, 2021, 11: 6120-6137. doi:  10.7150/thno.54881
    [19] Patel RB, Hernandez R, Carlson P, et al. Low-dose targeted radionuclide therapy renders immunologically cold tumors responsive to immune checkpoint blockade[J]. Sci Transl Med, 2021, 13: eabb3631. doi:  10.1126/scitranslmed.abb3631
    [20] Grzmil M, Boersema P, Sharma A, et al. Comparative analysis of cancer cell responses to targeted radionuclide therapy (TRT) and external beam radiotherapy (EBRT)[J]. J Hematol Oncol, 2022, 15: 123. doi:  10.1186/s13045-022-01343-y
    [21] Zhang J, Yang M, Fan X, et al. Biomimetic radiosensitizers unlock radiogenetics for local interstitial radiotherapy to activate systematic immune responses and resist tumor metastasis[J]. J Nanobiotechnology, 2022, 20: 103. doi:  10.1186/s12951-022-01324-w
    [22] Brown R, Hernandez R, Grudzinski JJ, et al. Ability of Molecular Targeted Radionucleotide Therapy and Anti-CTLA-4 to Prevent Spontaneous Metastases in a Preclinical Lewis Lung Carcinoma Model[J]. Int J Radiat Oncol Biol Phys, 2019, 105: E498-E499.
    [23] Potluri HK, Ferreira CA, Grudzinski J, et al. Antitumor efficacy of 90Y-NM600 targeted radionuclide therapy and PD-1 blockade is limited by regulatory T cells in murine prostate tumors[J]. J Immunother Cancer, 2022, 10: e005060. doi:  10.1136/jitc-2022-005060
    [24] Lutetium (Lu-177) Dotatate Approved by FDA[J]. Cancer Discov, 2018, 8: OF2.
    [25] Fallah J, Agrawal S, Gittleman H, et al. FDA Approval Summary: lutetium (Lu-177) vipivotide tetraxetan for patients with metastatic castration-resistant prostate cancer[J]. Clin Cancer Res, 2023, 29: 1651-1657. doi:  10.1158/1078-0432.CCR-22-2875
    [26] Kim C, Liu SV, Subramaniam DS, et al. Phase Ⅰ study of the 177Lu-DOTA(0)-Tyr(3)-Octreotate (lutathera) in combination with nivolumab in patients with neuroendocrine tumors of the lung[J]. J Immunother Cancer, 2020, 8: e000980. doi:  10.1136/jitc-2020-000980
    [27] Ferdinandus J, Fendler WP, Lueckerath K, et al. Response to Combined Peptide Receptor Radionuclide Therapy and Checkpoint Immunotherapy with Ipilimumab Plus Nivolumab in Metastatic Merkel Cell Carcinoma[J]. J Nucl Med, 2022, 63: 396-398. doi:  10.2967/jnumed.121.262344
    [28] Lin AL, Tabar V, Young RJ, et al. Synergism of Checkpoint Inhibitors and Peptide Receptor Radionuclide Therapy in the Treatment of Pituitary Carcinoma[J]. J Endocr Soc, 2021, 5: bvab133. doi:  10.1210/jendso/bvab133
    [29] Prasad V, Zengerling F, Steinacker JP, et al. First Experiences with 177Lu-PSMA Therapy in Combination with Pembrolizumab or After Pretreatment with Olaparib in Single Patients[J]. J Nucl Med, 2021, 62: 975-978. doi:  10.2967/jnumed.120.249029
    [30] Chen H, Zhao L, Fu K, et al. Integrin αυβ3-targeted radionuclide therapy combined with immune checkpoint blockade immunotherapy synergis-tically enhances anti-tumor efficacy[J]. Theranostics, 2019, 9: 7948-7960. doi:  10.7150/thno.39203
    [31] Wen XJ, Zeng XY, Shi CR, et al. Optimum combination of radiopharmaceuticals-based targeting-triggering-therapy effect and PD-L1 blockade immunotherapy[J]. Adv Ther, 2022, 6: 2200193.
    [32] Wen X, Zeng X, Liu J, et al. Synergism of 64Cu-Labeled RGD with Anti-PD-L1 Immunotherapy for the Long-Acting Antitumor Effect[J]. Bioconjug Chem, 2022, 33: 2170-2179. doi:  10.1021/acs.bioconjchem.2c00408
    [33] Guzik P, Siwowska K, Fang HY, et al. Promising potential of [177Lu]Lu-DOTA-folate to enhance tumor response to immunotherapy-a preclinical study using a syngeneic breast cancer model[J]. Eur J Nucl Med Mol Imaging, 2021, 48: 984-994. doi:  10.1007/s00259-020-05054-9
    [34] Ren J, Xu M, Chen J, et al. PET imaging facilitates antibody screening for synergistic radioimmunotherapy with a 177Lu-labeled alphaPD-L1 antibody[J]. Theranostics, 2021, 11: 304-315. doi:  10.7150/thno.45540
    [35] Malo ME, Allen KJH, Jiao R, et al. Mechanistic Insights into Synergy between Melanin-Targeting Radioimmun-otherapy and Immunotherapy in Experimental Melanoma[J]. Int J Mol Sci, 2020, 21: 8721. doi:  10.3390/ijms21228721
    [36] Choi J, Beaino W, Fecek RJ, et al. Combined VLA-4-Targeted Radionuclide Therapy and Immunotherapy in a Mouse Model of Melanoma[J]. J Nucl Med, 2018, 59: 1843-1849. doi:  10.2967/jnumed.118.209510
    [37] Vito A, Rathmann S, Mercanti N, et al. Combined Radionuclide Therapy and Immunotherapy for Treatment of Triple Negative Breast Cancer[J]. Int J Mol Sci, 2021, 22: 4843. doi:  10.3390/ijms22094843
    [38] Stap J, Krawczyk PM, Van Oven CH, et al. Induction of linear tracks of DNA double-strand breaks by alpha-particle irradiation of cells[J]. Nat Methods, 2008, 5: 261-266. doi:  10.1038/nmeth.f.206
    [39] Czernin J, Current K, Mona CE, et al. Immune-Checkpoint Blockade Enhances 225Ac-PSMA617 Efficacy in a Mouse Model of Prostate Cancer[J]. J Nucl Med, 2021, 62: 228-231. doi:  10.2967/jnumed.120.246041
    [40] Josefsson A, Nedrow JR, Park S, et al. Combining alpha-particle radiopharmaceutical therapy using Actinium-225 and immunotherapy with anti-PD-L1 antibodies in a murine immunocompetent metastatic breast cancer model[J]. Cancer Res, 2016, 76: 3052. doi:  10.1158/1538-7445.AM2016-3052
    [41] Dabagian H, Taghvaee T, Martorano P, et al. PARP Targeted Alpha-Particle Therapy Enhances Response to PD-1 Immune-Checkpoint Blockade in a Syngeneic Mouse Model of Glioblastoma[J]. ACS Pharmacol Transl Sci, 2021, 4: 344-351. doi:  10.1021/acsptsci.0c00206
    [42] Zhang J, Li F, Yin Y, et al. Alpha radionuclide-chelated radioimmunotherapy promoters enable local radiotherapy/chemodynamic therapy to discourage cancer progression[J]. Biomater Res, 2022, 26: 44. doi:  10.1186/s40824-022-00290-6
    [43] Malamas AS, Gameiro SR, Knudson KM, et al. Sublethal exposure to alpha radiation 223Ra dichloride) enhances various carcinomas' sensitivity to lysis by antigen-specific cytotoxic T lymphocytes through calreticulin-mediated immunogenic modulation[J]. Oncotarget, 2016, 7: 86937-86947. doi:  10.18632/oncotarget.13520
    [44] Creemers JHA, van der Doelen MJ, van Wilpe S, et al. Immunophenotyping Reveals Longitudinal Changes in Circulating Immune Cells During Radium-223 Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer[J]. Front Oncol, 2021, 11: 667658. doi:  10.3389/fonc.2021.667658
    [45] Vardaki I, Corn P, Gentile E, et al. Radium-223 Treatment Increases Immune Checkpoint Expression in Extracellular Vesicles from the Metastatic Prostate Cancer Bone Microenvironment[J]. Clin Cancer Res, 2021, 27: 3253-3264. doi:  10.1158/1078-0432.CCR-20-4790
    [46] Fong L, Morris MJ, Sartor O, et al. A Phase Ib Study of Atezolizumab with Radium-223 Dichloride in Men with Metastatic Castration-Resistant Prostate Cancer[J]. Clin Cancer Res, 2021, 27: 4746-4756. doi:  10.1158/1078-0432.CCR-21-0063
    [47] Li M, Liu D, Lee D, et al. Targeted Alpha-Particle Radiotherapy and Immune Checkpoint Inhibitors Induces Cooperative Inhibition on Tumor Growth of Malignant Melanoma[J]. Cancers (Basel), 2021, 13: 3676. doi:  10.3390/cancers13153676
    [48] Nosanchuk JD, Jeyakumar A, Ray A, et al. Structure-function analysis and therapeutic efficacy of antibodies to fungal melanin for melanoma radioimmunotherapy[J]. Sci Rep, 2018, 8: 5466. doi:  10.1038/s41598-018-23889-z
    [49] Perrin J, Capitao M, Allard M, et al. Targeted Alpha Particle Therapy Remodels the Tumor Microenvironment and Improves Efficacy of Immunotherapy[J]. Int J Radiat Oncol Biol Phys, 2022, 112: 790-801. doi:  10.1016/j.ijrobp.2021.10.013
    [50] Gorin JB, Menager J, Gouard S, et al. Antitumor immunity induced after alpha irradiation[J]. Neoplasia, 2014, 16: 319-328. doi:  10.1016/j.neo.2014.04.002
    [51] Lejeune P, Cruciani V, Berg-Larsen A, et al. Immunostimulatory effects of targeted thorium-227 conjugates as single agent and in combination with anti-PD-L1 therapy[J]. J Immunother Cancer, 2021, 9: e002387. doi:  10.1136/jitc-2021-002387
    [52] Hagemann UB, Ellingsen C, Schuhmacher J, et al. Mesothelin-Targeted Thorium-227 Conjugate (MSLN-TTC): Preclinical Evaluation of a New Targeted Alpha Therapy for Mesothelin-Positive Cancers[J]. Clin Cancer Res, 2019, 25: 4723-4734. doi:  10.1158/1078-0432.CCR-18-3476
    [53] Moadel RM, Nguyen AV, Lin EY, et al. Positron emission tomography agent 2-deoxy-2-[18F]fluoro-D-glucose has a therapeutic potential in breast cancer[J]. Breast Cancer Res, 2003, 5: R199-R205. doi:  10.1186/bcr643
    [54] Moadel RM, Weldon RH, Katz EB, et al. Positherapy: targeted nuclear therapy of breast cancer with 18F-2-deoxy-2-fluoro-D-glucose[J]. Cancer Res, 2005, 65: 698-702. doi:  10.1158/0008-5472.698.65.3
    [55] Fang S, Wang J, Jiang H, et al. Experimental study on the therapeutic effect of positron emission tomography agent[18F]-labeled 2-deoxy-2-fluoro-d-glucose in a colon cancer mouse model[J]. Cancer Biother Radiopharm, 2010, 25: 733-740.
    [56] Wen X, Shi C, Zeng X, et al. A Paradigm of Cancer Immunotherapy Based on 2-[18F]FDG and Anti-PD-L1 mAb Combination to Enhance the Antitumor Effect[J]. Clin Cancer Res, 2022, 28: 2923-2937. doi:  10.1158/1078-0432.CCR-22-0159
    [57] 文雪君, 周吴昊, 郭志德, 等. 整合素αυβ3靶向放射性药物99mTc-RGD联合抗PD-L1肿瘤免疫治疗增强抗肿瘤效果的研究[J]. 协和医学杂志, 2023, 14: 766-773. doi:  10.12290/xhyxzz.2023-0155
    [58] Wen X, Zeng X, Cheng X, et al. PD-L1-Targeted Radionuclide Therapy Combined with alpha PD-L1 Antibody Immunotherapy Synergistically Improves the Antitumor Effect[J]. Mol Pharm, 2022, 19: 3612-3622. doi:  10.1021/acs.molpharmaceut.2c00281
    [59] Gutfilen B, Souza SA, Valentini G. Copper-64: a real theranostic agent[J]. Drug Des Devel Ther, 2018, 12: 3235-3245. doi:  10.2147/DDDT.S170879
  • 加载中
图(3) / 表(1)
计量
  • 文章访问数:  1789
  • HTML全文浏览量:  136
  • PDF下载量:  127
  • 被引次数: 0
出版历程
  • 收稿日期:  2023-03-29
  • 录用日期:  2023-04-17
  • 网络出版日期:  2023-05-18
  • 刊出日期:  2023-07-30

目录

    /

    返回文章
    返回

    【温馨提醒】近日,《协和医学杂志》编辑部接到作者反映,有多名不法人员冒充期刊编辑发送见刊通知,鼓动作者添加微信,从而骗取版面费的行为。特提醒您,本刊与作者联系的方式均为邮件通知或电话,稿件进度通知邮箱为:mjpumch@126.com,编辑部电话为:010-69154261,请提高警惕,谨防上当受骗!如有任何疑问,请致电编辑部核实。谢谢!