Mechanistic study on synergistic photo-immunological effects of laser immunotherapy for metastatic cancers
激光免疫治疗转移癌协同光免疫效应的机制研究
基本信息
- 批准号:10249219
- 负责人:
- 金额:$ 35.46万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-08-04 至 2023-07-31
- 项目状态:已结题
- 来源:
- 关键词:3-Dimensional4T1AftercareAnimalsAntigen PresentationAntigen TargetingAntigen-Presenting CellsAntigensAutologousCancer PatientCancer VaccinesCell DeathCessation of lifeClinical TrialsComplementary therapiesCytotoxic T-LymphocytesDendritic CellsDevelopmentDisseminated Malignant NeoplasmDistantDistant MetastasisDoseFaceFoundationsGenerationsGoalsImmune checkpoint inhibitorImmune responseImmune systemImmunityImmunizationImmunologic AdjuvantsImmunologicsImmunotherapyIn SituLasersMagnetic ResonanceMalignant NeoplasmsMammary NeoplasmsMetastatic Neoplasm to the LungModalityMolecularMonitorMusNeoplasm MetastasisPatientsPatternPrimary NeoplasmProcessProductionSiteSourceT cell responseT-Cell ActivationT-LymphocyteT-Lymphocyte SubsetsTemperatureTestingTherapeutic EffectThermometryTreatment FailureTumor AntigensTumor ImmunityTumor TissueTumor-infiltrating immune cellsanti-tumor immune responseanticancer researchantitumor effectbasecancer therapycell injurycheckpoint inhibitioncheckpoint therapyconventional therapyeffective therapyglycated chitosanimmunogenicimmunogenicityimmunoreactionindividualized medicineinnovationirradiationlymph nodesmalignant breast neoplasmmelanomaneoplastic cellnovelphotothermal therapypreclinical studyresponsesuccesstargeted treatmenttreatment strategytumortumor-immune system interactionsuptake
项目摘要
Project Summary
Metastasis causes treatment failure and 90% of cancer-related deaths. We have developed laser
immunotherapy (LIT) for the treatment of metastatic cancers. LIT combines local laser photothermal
therapy (PTT) and immunotherapy using glycated chitosan (GC), a novel immunoadjuvant, to induce
systemic antitumor immune responses. LIT has shown success in clinical trials for late-stage, metastatic
cancer patients who had failed conventional treatment modalities. Specifically, LIT has demonstrated its ability
to eliminate treated primary tumors and eradicate untreated metastases at distant sites. However, the
mechanism of LIT, particularly how it controls tumor metastases, has not been fully investigated. Based on our
previous studies, we believe that PTT and GC each induces unique immunological reactions, which, when
synergized, produce a systemic, long-term antitumor immunity. Specifically, we hypothesize that: 1) PTT
induces immunogenic tumor cell death (ICD), providing antigen sources and damage-associated molecular
patterns (DAMPs) to trigger host antitumor immune responses; 2) GC enhances uptake and presentation of
antigens generated by PTT-induced ICD, amplifying antitumor T cell response; and 3) LIT synergizes and
amplifies the immune responses induced by PTT and GC, particularly when combined with other
immunotherapies, such as checkpoint inhibition, providing potent, systemic therapeutic effects, especially on
tumor metastases. To test these hypotheses, we plan to achieve the following aims: (1) to determine the
photothermal-immunological effects of PTT by determining temperature distribution in tumor tissue and by
characterizing the ICD and DAMPs generated by PTT; (2) to determine the effects of GC on immune system
during LIT, particularly on activation of T cell as well as enhancement of antigen uptake and presentation; and
(3) to determine the effects of LIT, as well as the combination of LIT and checkpoint inhibition, on the
enhancement of tumor immunogenicity and on controlling tumor metastasis. The successful completion of this
project will achieve the following goals: (1) to obtain a comprehensive understanding of the immunological
mechanism of LIT in eliminating and inhibiting metastases; (2) to lay the foundation necessary to advance LIT
into an effective treatment modality for patients with a variety of metastatic cancers; (3) to facilitate the
development of new, novel treatment strategies using synergistic immunological mechanisms similar to that of
LIT, in combination with other complementary therapies, for patients with metastatic cancers.
项目摘要
转移导致治疗失败和90%的癌症相关死亡。我们开发了激光
免疫疗法(LIT)用于治疗转移性癌症。LIT结合了局部激光光热
治疗(PTT)和免疫治疗使用糖化壳聚糖(GC),一种新的免疫佐剂,以诱导,
全身抗肿瘤免疫反应。LIT在晚期转移性肿瘤的临床试验中取得了成功,
传统治疗方式失败的癌症患者。具体来说,LIT已经证明了它的能力,
以消除治疗的原发性肿瘤和根除远处未治疗的转移。但
LIT的机制,特别是它如何控制肿瘤转移,尚未得到充分研究。基于我们
以前的研究,我们认为,PTT和GC各自诱导独特的免疫反应,当
协同作用,产生系统性、长期抗肿瘤免疫。具体来说,我们假设:1)PTT
诱导免疫原性肿瘤细胞死亡(ICD),提供抗原来源和损伤相关分子
2)GC增强了免疫应答的摄取和呈递,
由PTT诱导的ICD产生的抗原,放大抗肿瘤T细胞应答;和3)LIT协同和
增强由PTT和GC诱导的免疫应答,特别是当与其他
免疫疗法,如检查点抑制,提供有效的全身治疗效果,特别是对
肿瘤转移为了验证这些假设,我们计划实现以下目标:(1)确定
通过测定肿瘤组织中的温度分布和通过测定PTT的光热免疫效应,
分析PTT产生的ICD和DAMP的特性;(2)确定GC对免疫系统的影响
在LIT期间,特别是对T细胞的活化以及抗原摄取和呈递的增强;以及
(3)为了确定LIT以及LIT和检查点抑制的组合对
增强肿瘤免疫原性和控制肿瘤转移。成功完成本
项目将实现以下目标:(1)全面了解免疫学
LIT消除和抑制转移的机制;(2)为推进LIT奠定必要的基础
为患有各种转移性癌症的患者提供有效的治疗方式;(3)促进
开发新的、新颖的治疗策略,其使用类似于以下的协同免疫机制:
LIT与其他补充疗法联合用于转移性癌症患者。
项目成果
期刊论文数量(15)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Transcriptomic analysis of mechanism of melanoma cell death induced by photothermal therapy.
光热疗法诱导黑色素瘤细胞死亡机制的转录组分析
- DOI:10.1002/jbio.202100034
- 发表时间:2021-08
- 期刊:
- 影响因子:2.8
- 作者:Yan G;Shi L;Zhang F;Luo M;Zhang G;Liu P;Liu K;Chen WR;Wang X
- 通讯作者:Wang X
An Immunologically Modified Nanosystem Based on Noncovalent Binding Between Single-Walled Carbon Nanotubes and Glycated Chitosan.
- DOI:10.1177/1533033818802313
- 发表时间:2018-01-01
- 期刊:
- 影响因子:2.8
- 作者:Saha LC;Nag OK;Doughty A;Liu H;Chen WR
- 通讯作者:Chen WR
Novel Immune Stimulant Amplifies Direct Tumoricidal Effect of Cancer Ablation Therapies and Their Systemic Antitumor Immune Efficacy.
- DOI:10.3390/cells10030492
- 发表时间:2021-02-25
- 期刊:
- 影响因子:6
- 作者:Korbelik M;Hode T;Lam SSK;Chen WR
- 通讯作者:Chen WR
Monitoring tissue temperature during photothermal therapy for cancer.
- DOI:10.1097/jbr.0000000000000050
- 发表时间:2019-12
- 期刊:
- 影响因子:0
- 作者:West CL;Doughty ACV;Liu K;Chen WR
- 通讯作者:Chen WR
Single-cell RNA sequencing reveals localized tumour ablation and intratumoural immunostimulant delivery potentiate T cell mediated tumour killing.
- DOI:10.1002/ctm2.937
- 发表时间:2022-07
- 期刊:
- 影响因子:10.6
- 作者:Hoover, Ashley R.;Liu, Kaili;DeVette, Christa I.;Krawic, Jason R.;Medcalf, Alexandra D.;West, Connor L.;Hode, Tomas;Lam, Samuel S. K.;Welm, Alana L.;Sun, Xiao-Hong;Hildebrand, William H.;Chen, Wei R.
- 通讯作者:Chen, Wei R.
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Wei R. Chen其他文献
Immunological responses induced by the combination of phototherapy and immunotherapy in the treatment of metastatic tumors
光疗和免疫疗法联合治疗转移性肿瘤诱导的免疫反应
- DOI:
- 发表时间:
2008 - 期刊:
- 影响因子:0
- 作者:
Wei R. Chen;M. Naylor;R. Nordquist;T. Teague;Hong Liu - 通讯作者:
Hong Liu
Induction and detection of immune responses by photoimmunotherapy
光免疫疗法诱导和检测免疫反应
- DOI:
- 发表时间:
2005 - 期刊:
- 影响因子:0
- 作者:
Wei R. Chen;K. Bartels;Hong Liu;R. Nordquist - 通讯作者:
R. Nordquist
Monitoring of laser treatment of rat tumors using digital x-ray imaging technique
使用数字 X 射线成像技术监测激光治疗大鼠肿瘤
- DOI:
- 发表时间:
2002 - 期刊:
- 影响因子:0
- 作者:
Wei R. Chen;Hong Liu;R. Nordquist - 通讯作者:
R. Nordquist
The combination of radiotherapy and immunotherapy using glycated chitosan as an immunological stimulant
以糖化壳聚糖作为免疫刺激剂的放射治疗与免疫治疗相结合
- DOI:
10.1117/12.2080950 - 发表时间:
2015 - 期刊:
- 影响因子:6.4
- 作者:
Chun;J. Leu;Chung‐Yi Wang;Wei R. Chen;Yi - 通讯作者:
Yi
The correlation study of temperature distribution with the immunology response under laser radiation
激光辐射下温度分布与免疫反应的相关性研究
- DOI:
- 发表时间:
2008 - 期刊:
- 影响因子:0
- 作者:
Yichao Chen;R. Nordquist;M. Naylor;Feng Wu;Hong Liu;Y. Tesiram;Andrew Abbott;R. Towner;Wei R. Chen - 通讯作者:
Wei R. Chen
Wei R. Chen的其他文献
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{{ truncateString('Wei R. Chen', 18)}}的其他基金
Potentiating a systemic antitumor response by interstitial localized ablative immunotherapy to synergize with immune checkpoint therapy for metastatic pancreatic tumors
通过间质局部消融免疫疗法增强全身抗肿瘤反应,与转移性胰腺肿瘤的免疫检查点疗法协同作用
- 批准号:
10580071 - 财政年份:2022
- 资助金额:
$ 35.46万 - 项目类别:
Mechanistic study on synergistic photo-immunological effects of laser immunotherapy for metastatic cancers
激光免疫治疗转移癌协同光免疫效应的机制研究
- 批准号:
9750020 - 财政年份:2017
- 资助金额:
$ 35.46万 - 项目类别:
Mechanistic study on synergistic photo-immunological effects of laser immunotherapy for metastatic cancers
激光免疫治疗转移癌协同光免疫效应的机制研究
- 批准号:
9980306 - 财政年份:2017
- 资助金额:
$ 35.46万 - 项目类别:
A Novel Multifunctional Bionanoprobe-Based Phototherapy for Metastatic Cancers
一种新型多功能生物纳米探针光疗治疗转移性癌症
- 批准号:
8581730 - 财政年份:2013
- 资助金额:
$ 35.46万 - 项目类别:
A Novel Multifunctional Bionanoprobe-Based Phototherapy for Metastatic Cancers
一种新型多功能生物纳米探针光疗治疗转移性癌症
- 批准号:
8702169 - 财政年份:2013
- 资助金额:
$ 35.46万 - 项目类别:
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