Anti-CTLA-4 and anti-PD-1 immunotherapies repress tumor progression in preclinical breast and colon model with independent regulatory T cells response

Rupp, Tristan; Genest, Laurie; Babin, David; Legrand, Christophe; Hunault, Marion; Froget, Guillaume; Castagné, Vincent

doi:10.1016/j.tranon.2022.101405

Cited by 31 publications

(29 citation statements)

References 73 publications

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“…The procedure for subcutaneous graft is adapted from [ 29 , 83 ]. 5 × 10 6 A549 cells, 5 × 10 6 KLN205, or 5 × 10 5 LLC1 cells were injected subcutaneously into the right flank of the mice, respectively in BALB/c-nude, DBA/2JRj, or C57BL/6JRj.…”

Section: Methodsmentioning

confidence: 99%

Therapeutic Potential of Fingolimod and Dimethyl Fumarate in Non-Small Cell Lung Cancer Preclinical Models

Rupp

Debasly

Genest

et al. 2022

IJMS

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New therapies are required for patients with non-small cell lung cancer (NSCLC) for which the current standards of care poorly affect the patient prognosis of this aggressive cancer subtype. In this preclinical study, we aim to investigate the efficacy of Fingolimod, a described inhibitor of sphingosine-1-phosphate (S1P)/S1P receptors axis, and Dimethyl Fumarate (DMF), a methyl ester of fumaric acid, both already approved as immunomodulators in auto-immune diseases with additional expected anti-cancer effects. The impact of both drugs was analyzed with in vitro cell survival analysis and in vivo graft models using mouse and human NSCLC cells implanted in immunocompetent or immunodeficient mice, respectively. We demonstrated that Fingolimod and DMF repressed tumor progression without apparent adverse effects in vivo in three preclinical mouse NSCLC models. In vitro, Fingolimod did not affect either the tumor proliferation or the cytotoxicity, although DMF reduced tumor cell proliferation. These results suggest that Fingolimod and DMF affected tumor progression through different cellular mechanisms within the tumor microenvironment. Fingolimod and DMF might uncover potential therapeutic opportunities in NSCLC.

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Section: Methodsmentioning

confidence: 99%

Therapeutic Potential of Fingolimod and Dimethyl Fumarate in Non-Small Cell Lung Cancer Preclinical Models

Rupp

Debasly

Genest

et al. 2022

IJMS

Self Cite

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“…The procedure was adapted from [ 21 , 22 ]. All methods, designed to minimize animal suffering and to ensure good quality of biological samples, were adapted from basic procedures commonly used in studies performed in rodents.…”

Section: Methodsmentioning

confidence: 99%

“…Only mycoplasma-negative cell lines were used for the experimentation included in this study. The procedure was adapted from [ 21 , 22 ]. Cells were grown in cell incubator at 37 °C and 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

“…A total of 5 × 10 6 PC-9/CR or 5 × 10 5 U118MG cells were injected into BALB/c-nude mice. The procedure was adapted from [ 21 , 22 ]. The cells to be implanted were resuspended in sterile PBS and kept on ice.…”

Section: Methodsmentioning

confidence: 99%

“…The procedure was adapted from [ 21 , 22 ]. Statistical analysis and graphical representations were performed using GraphPad Prism (version 9.2.0).…”

Section: Methodsmentioning

confidence: 99%

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A Face-To-Face Comparison of Tumor Chicken Chorioallantoic Membrane (TCAM) In Ovo with Murine Models for Early Evaluation of Cancer Therapy and Early Drug Toxicity

Rupp

Legrand

Hunault

et al. 2022

Cancers

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Ethical considerations, cost, and time constraints have highlighted the need to develop alternatives to rodent in vivo models for evaluating drug candidates for cancer. The tumor chicken chorioallantoic membrane (TCAM) model provides an affordable and fast assay that permits direct visualization of tumor progression. Tumors from multiple species including rodents and human cell lines can be engrafted. In this study, we engrafted several tumor models onto the CAM and demonstrated that the TCAM model is an alternative to mouse models for preliminary cancer drug efficacy testing and toxicity analysis. Tumor cells were deposited onto CAM, and then grown for up to an additional 10 days before chronic treatments were administered. The drug response of anticancer therapies was screened in 12 tumor cell lines including glioblastoma, melanoma, breast, prostate, colorectal, liver, and lung cancer. Tumor-bearing eggs and tumor-bearing mice had a similar chemotherapy response (cisplatin and temozolomide) in four human and mouse tumor models. We also demonstrated that lethality observed in chicken embryos following chemotherapies such as cisplatin and cyclophosphamide were associated with corresponding side-effects in mice with body weight loss. According to our work, TCAM represents a relevant alternative model to mice in early preclinical oncology screening, providing insights for both the efficacy and the toxicity of anticancer drugs.

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Membrane Fusion Liposomes Deliver Antifibrotic and Chemotherapeutic Drugs Sequentially to Enhance Tumor Treatment Efficacy by Reshaping Tumor Microenvironment

Jia,

Wang,

et al. 2024

Adv Healthcare Materials

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The intricate tumor microenvironment in triple‐negative breast cancer (TNBC) hampers chemotherapy and immunotherapy efficacy due to dense extracellular matrix (ECM) by tumor‐associated fibroblasts (TAFs). Nanoparticle‐based therapies, especially “all in one” nanoparticles, have shown great potential in combined drug delivery strategies to reshape the tumor microenvironment and enhance therapeutic efficiency. However, these “all in one” nanoparticles suffer from limitations in targeting different target cells, uncontrollable dosing ratio, and disregarding the impact of delivery schedules. This study prepared cell membrane fusion liposomes (TAFsomes and CCMsomes) to load FDA‐approved anti‐fibrotic drug pirfenidone (PFD/TAFsomes) and anti‐tumor drug doxorubicin (DOX/CCMsomes). These liposomes can specifically target TAFs cells and tumor cells, and combined administration can effectively inhibit TAF activity, reshape the TME, and significantly enhance the tumor chemotherapy efficacy. Combined drug delivery defeats “all in one” liposomes (DOX/PFD/Liposomes, DOX/PFD/TAFsomes, and DOX/PFD/CCMsomes) by flexibly adjusting the drug delivery ratio. Moreover, an asynchronous delivery strategy that optimizes the administration schedule not only further improves the therapeutic effect, but also amplifies the effectiveness of α‐PD‐L1 immunotherapy by modulating the tumor immune microenvironment. This delivery strategy provides a personalized treatment approach with clinical translation potential, providing new ideas for enhancing the therapeutic effect against solid tumors such as TNBC.This article is protected by copyright. All rights reserved

show abstract

Anti-CTLA-4 and anti-PD-1 immunotherapies repress tumor progression in preclinical breast and colon model with independent regulatory T cells response

Cited by 31 publications

References 73 publications

Therapeutic Potential of Fingolimod and Dimethyl Fumarate in Non-Small Cell Lung Cancer Preclinical Models

Therapeutic Potential of Fingolimod and Dimethyl Fumarate in Non-Small Cell Lung Cancer Preclinical Models

A Face-To-Face Comparison of Tumor Chicken Chorioallantoic Membrane (TCAM) In Ovo with Murine Models for Early Evaluation of Cancer Therapy and Early Drug Toxicity

Membrane Fusion Liposomes Deliver Antifibrotic and Chemotherapeutic Drugs Sequentially to Enhance Tumor Treatment Efficacy by Reshaping Tumor Microenvironment

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