Cisplatin nanoparticles boost abscopal effect of radiation plus anti-PD1 therapy

Wang, Ying; Shen, Na; Wang, Yue; Li, Mo; Zhang, Wanze; Fan, Liwen; Liu, Linlin; Tang, Zhaohui; Chen, Xuesi

doi:10.1039/d1bm00112d

Cited by 19 publications

(14 citation statements)

References 39 publications

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“… 423 Of note, Wang et al reported that cisplatin nanoparticles can promote the abscopal effect induced by RT with PD1 inhibitors which breaks through the efficiency limitation of iRT. 424 …”

Section: Clinical Practicementioning

confidence: 99%

Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Zhang

Liu

Chen

et al. 2022

Sig Transduct Target Ther

239

141

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Radiotherapy (RT) is delivered for purposes of local control, but can also exert systemic effect on remote and non-irradiated tumor deposits, which is called abscopal effect. The view of RT as a simple local treatment has dramatically changed in recent years, and it is now widely accepted that RT can provoke a systemic immune response which gives a strong rationale for the combination of RT and immunotherapy (iRT). Nevertheless, several points remain to be addressed such as the interaction of RT and immune system, the identification of the best schedules for combination with immunotherapy (IO), the expansion of abscopal effect and the mechanism to amplify iRT. To answer these crucial questions, we roundly summarize underlying rationale showing the whole immune landscape in RT and clinical trials to attempt to identify the best schedules of iRT. In consideration of the rarity of abscopal effect, we propose that the occurrence of abscopal effect induced by radiation can be promoted to 100% in view of molecular and genetic level. Furthermore, the “radscopal effect” which refers to using low-dose radiation to reprogram the tumor microenvironment may amplify the occurrence of abscopal effect and overcome the resistance of iRT. Taken together, RT could be regarded as a trigger of systemic antitumor immune response, and with the help of IO can be used as a radical and systemic treatment and be added into current standard regimen of patients with metastatic cancer.

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Section: Clinical Practicementioning

confidence: 99%

Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Zhang

Liu

Chen

et al. 2022

Sig Transduct Target Ther

239

141

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“…First, we selected doses of 7 mg/kg for CDDP and 15 mg/kg for CDDP-NPs (eq to CDDP) as they have similar toxicity . Second, since CDDP-NPs have prolonged blood circulation, greater accumulation, and more Pt-DNA adducts , in a tumor at 72 h, the superior host immune response would probably last for a prolonged duration. Thus, 72 h was selected as the appropriate time point to investigate the superior host immune response of CDDP-NPs compared to CDDP.…”

Section: Resultsmentioning

confidence: 99%

Cisplatin Nanoparticles Promote Intratumoral CD8⁺ T Cell Priming via Antigen Presentation and T Cell Receptor Crosstalk

Yao

Shen

et al. 2022

Nano Lett.

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Nanomedicines are highly promising for cancer therapy due to their minimal side effects. However, little is known regarding their host immune response, which may limit their clinical efficacy and applications. Here, we find that cisplatin (CDDP)-loaded poly(l-glutamic acid)-graft-methoxy poly(ethylene glycol) complex nanoparticles (CDDP-NPs) elicit a strong antitumor CD8+ T cell-mediated immune response in a tumor-bearing mouse model compared to free CDDP. Mechanistically, the sustained retention of CDDP-NPs results in persistent tumor MHC-I overexpression, which promotes the formation of MHC-I-antigen peptide complex (pMHC-I), enhances the interaction between pMHC-I and T cell receptor (TCR), and leads to the activation of TCR signaling pathway and CD8+ T cell-mediated immune response. Furthermore, CDDP-NPs upregulate the costimulatory OX40 on intratumoral CD8+ T cells, and synergize with the agonistic OX40 antibody (aOX40) to suppress tumor growth by 89.2%. Our study provides a basis for the efficacy advantage of CDDP-based nanomedicines and immunotherapy.

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“…This is due to the enhanced immune response and abscopal effects. [ 253 ] Additionally, the srNPs synergistic immunotherapy for training immune cells can produce specific antibodies to establish immune memory to inhibit the recurrence of cancer in the cradle. [ 254 ] Notably, m‐srNPs responsive to external and internal stimuli are more effective and intelligent in regulating drug release than single responsive systems.…”

Section: Discussionmentioning

confidence: 99%

Stimuli‐Responsive Nanoparticles for Controlled Drug Delivery in Synergistic Cancer Immunotherapy

Zhang

Lin

Lin³

et al. 2021

Advanced Science

138

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Cancer immunotherapy has achieved promising clinical progress over the recent years for its potential to treat metastatic tumors and inhibit their recurrences effectively. However, low patient response rates and dose-limiting toxicity remain as major dilemmas for immunotherapy. Stimuli-responsive nanoparticles (srNPs) combined with immunotherapy offer the possibility to amplify anti-tumor immune responses, where the weak acidity, high concentration of glutathione, overexpressions of enzymes, and reactive oxygen species, and external stimuli in tumors act as triggers for controlled drug release. This review highlights the design of srNPs based on tumor microenvironment and/or external stimuli to combine with different anti-tumor drugs, especially the immunoregulatory agents, which eventually realize synergistic immunotherapy of malignant primary or metastatic tumors and acquire a long-term immune memory to prevent tumor recurrence. The authors hope that this review can provide theoretical guidance for the construction and clinical transformation of smart srNPs for controlled drug delivery in synergistic cancer immunotherapy.

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Cisplatin nanoparticles boost abscopal effect of radiation plus anti-PD1 therapy

Abstract: The abscopal effect of radiation therapy (RT) is clinically significant but occurs rarely. Although anti-programmed cell death protein 1 antibody (anti-PD1) is likely to enhance the abscopal effect in patients...

Cited by 19 publications

References 39 publications

Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Cisplatin Nanoparticles Promote Intratumoral CD8⁺ T Cell Priming via Antigen Presentation and T Cell Receptor Crosstalk

Stimuli‐Responsive Nanoparticles for Controlled Drug Delivery in Synergistic Cancer Immunotherapy

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Cisplatin nanoparticles boost abscopal effect of radiation plus anti-PD1 therapy

Abstract: The abscopal effect of radiation therapy (RT) is clinically significant but occurs rarely. Although anti-programmed cell death protein 1 antibody (anti-PD1) is likely to enhance the abscopal effect in patients...

Cited by 19 publications

References 39 publications

Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Radiotherapy combined with immunotherapy: the dawn of cancer treatment

Cisplatin Nanoparticles Promote Intratumoral CD8+ T Cell Priming via Antigen Presentation and T Cell Receptor Crosstalk

Stimuli‐Responsive Nanoparticles for Controlled Drug Delivery in Synergistic Cancer Immunotherapy

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Cisplatin Nanoparticles Promote Intratumoral CD8⁺ T Cell Priming via Antigen Presentation and T Cell Receptor Crosstalk