Fine-Tuning Tumor Endothelial Cells to Selectively Kill Cancer

Uldry, Émilie; Faes, Seraina; Demartines, Nicolas; Dormond, Olivier

doi:10.3390/ijms18071401

Cited by 22 publications

(30 citation statements)

References 129 publications

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“…In our study, we showed that LPA treatment results in increases of TILs. It has been reported that HEVs located in the tumor increase TILs (9,(31)(32)(33). However, LPA does not induce HEV-related molecules.…”

Section: Discussionmentioning

confidence: 93%

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LPA4-Mediated Vascular Network Formation Increases the Efficacy of Anti–PD-1 Therapy against Brain Tumors

et al. 2018

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The structure and function of tumor blood vessels profoundly affects the tumor microenvironment. Signals mediated through the lysophosphatidic acid receptor 4 (LPA4) promote vascular network formation to restore normal vascular barrier function in subcutaneous tumors and thus improve drug delivery. However, the characteristics of the vasculature vary by organ and tumor types, and how drug delivery and leukocyte trafficking are affected by modification of vascular function by LPA in different cancers is unclear. Here, we show that LPA4 activation promotes the formation of fine vascular structures in brain tumors. RhoA/ROCK signaling contributed to LPA-induced endothelial cell-cell adhesion, and RhoA/ROCK activity following LPA4 stimulation regulated expression of VCAM-1. This resulted in increased lymphocyte infiltration into the tumor. LPA improved delivery of exogenous IgG into brain tumors and enhanced the anticancer effect of antiprogrammed cell death-1 antibody therapy. These results indicate the effects of LPA on vascular structure and function apply not only to chemotherapy but also to immunotherapy.Significance: These findings demonstrate that lysophosphatidic acid, a lipid mediator, promotes development of a fine capillary network in brain tumors by inducing tightening of endothelial cell-to-cell adhesion, facilitating improved drug delivery, and lymphocyte penetration.

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Section: Discussionmentioning

confidence: 93%

“…S4F and S4G). It has been suggested that HEVs located in the tumor induce infiltration by lymphocytes (9,(31)(32)(33). Therefore, we tested whether LPA treatment also alters the expression of HEV-related molecules (Ccl19, Ccl21, Cxcl13, and Glycam1).…”

Section: Lpa Increases Tumor-infiltrating Lymphocytes In Brain Tumorsmentioning

confidence: 98%

LPA4-Mediated Vascular Network Formation Increases the Efficacy of Anti–PD-1 Therapy against Brain Tumors

et al. 2018

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“…Indeed, some anti-angiogenic therapies have been shown to enhance intratumoral trafficking of lymphocytes in some cancers, notably by increasing the expression of adhesion molecules involved in T cell homing and by increased chemokine expression (Tartour et al, 2011;Wu et al, 2016). Alternatively, several strategies have been explored to normalize tumor vasculature rather than blocking it to relieve hypoxia, which has been shown to impair T cell cytotoxic activities (Huang et al, 2013;Uldry et al, 2017).…”

Section: Targeting Tumor-associated Blood Endothelial Cells (Becs)mentioning

confidence: 99%

Engineering Targeting Materials for Therapeutic Cancer Vaccines

Briquez

Hauert

Titta³

et al. 2020

Front. Bioeng. Biotechnol.

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Therapeutic cancer vaccines constitute a valuable tool to educate the immune system to fight tumors and prevent cancer relapse. Nevertheless, the number of cancer vaccines in the clinic remains very limited to date, highlighting the need for further technology development. Recently, cancer vaccines have been improved by the use of materials, which can strongly enhance their intrinsic properties and biodistribution profile. Moreover, vaccine efficacy and safety can be substantially modulated through selection of the site at which they are delivered, which fosters the engineering of materials capable of targeting cancer vaccines to specific relevant sites, such as within the tumor or within lymphoid organs, to further optimize their immunotherapeutic effects. In this review, we aim to give the reader an overview of principles and current strategies to engineer therapeutic cancer vaccines, with a particular focus on the use of sitespecific targeting materials. We will first recall the goal of therapeutic cancer vaccination and the type of immune responses sought upon vaccination, before detailing key components of cancer vaccines. We will then present how materials can be engineered to enhance the vaccine's pharmacokinetic and pharmacodynamic properties. Finally, we will discuss the rationale for site-specific targeting of cancer vaccines and provide examples of current targeting technologies.

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“…They play a critical role in a variety of physiological and pathological processes [64,65]. The importance of ECs in the context of cancer has been extensively investigated [66]. In 1945 it was reported that, in an animal model, an engrafted tumor recruits capillaries from the host to support its feeding and growth [67].…”

Section: Development Of Antiangiogenic Santavac Vaccinesmentioning

confidence: 99%

“…In 1945 it was reported that, in an animal model, an engrafted tumor recruits capillaries from the host to support its feeding and growth [67]. This finding gave rise to an entire field of research aiming to inhibit new blood vessel formation [66]. Among these studies was vaccine development based on the discovery that endothelial antigens were overexpressed in tumors relative to peripheral tissues.…”

Section: Development Of Antiangiogenic Santavac Vaccinesmentioning

confidence: 99%

SANTAVACTM: Summary of Research and Development

Lokhov

Mkrtichyan

Mamikonyan³

et al. 2019

Vaccines

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SANTAVAC is an antigen composition developed via proteomics and cell culture technology that is intended for the development of cancer vaccines against various solid tumors. Its mechanism of action is based on the heterogeneity of endothelial cells, the polypeptides of which are similar to the surface antigens of tumor-vessel cells, allowing targeted destruction by vaccination. While research and development work with SANTAVAC is ongoing, the existing data provide strong evidence that allogeneic SANTAVAC is an ideal candidate for the development of cancer vaccines with significant efficacy and safety. The SANTAVAC compositions described here demonstrated the ability to inhibit the growth of tumor vessel-specific endothelial cells up to 60 fold, with minimal effect on normal vasculature. Innovation, background, description of product development, and summary of nonclinical studies with SANTAVAC to date are presented in this review.

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Fine-Tuning Tumor Endothelial Cells to Selectively Kill Cancer

Cited by 22 publications

References 129 publications

LPA4-Mediated Vascular Network Formation Increases the Efficacy of Anti–PD-1 Therapy against Brain Tumors

LPA4-Mediated Vascular Network Formation Increases the Efficacy of Anti–PD-1 Therapy against Brain Tumors

Engineering Targeting Materials for Therapeutic Cancer Vaccines

SANTAVACTM: Summary of Research and Development

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