Patient-Derived Head and Neck Cancer Organoids Recapitulate EGFR Expression Levels of Respective Tissues and Are Responsive to EGFR-Targeted Photodynamic Therapy

Driehuis, Else; Spelier, Sacha; Hernández, Irati Beltrán; Bree, Remco de; Willems, Stefan M.; Clevers, Hans; Oliveira, Sabrina

doi:10.3390/jcm8111880

Cited by 78 publications

(81 citation statements)

References 52 publications

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“…This last aspect is of particular interest since a local treatment such as PDT, making use of locally applied light at the tumor site, could develop systemic effects via the activation of the immune system. included: the A431 cell line that overexpresses EGFR and the scc-U8 cell line expressing moderate EGFR levels, which more closely resemble the in vivo levels [19,20]. With this in vivo mirroring in mind, a highly cytotoxic NB-PDT (LD100) and a mild treatment (LD50) are also compared here, since uneven light penetration and tumor heterogeneity would likely lead to different degrees of cytotoxicity in vivo.…”

Section: Introductionmentioning

confidence: 99%

The Potential of Nanobody-Targeted Photodynamic Therapy to Trigger Immune Responses

Hernández

Angelier

D’Ondes

et al. 2020

Cancers

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M.L.A.); a.dimaggio@students.uu.nl (A.D.M.); Y.Yu@uu.nl (Y.Y.)Abstract: Nanobody-targeted photodynamic therapy (NB-PDT) has been recently developed as a more tumor-selective approach rather than conventional photodynamic therapy (PDT). NB-PDT uses nanobodies that bind to tumor cells with high affinity, to selectively deliver a photosensitizer, i.e., a chemical which becomes cytotoxic when excited with light of a particular wavelength. Conventional PDT has been reported to be able to induce immunogenic cell death, characterized by the exposure/release of damage-associated molecular patterns (DAMPs) from dying cells, which can lead to antitumor immunity. We explored this aspect in the context of NB-PDT, targeting the epidermal growth factor receptor (EGFR), using high and moderate EGFR-expressing cells. Here we report that, after NB-PDT, the cytoplasmic DAMP HSP70 was detected on the cell membrane of tumor cells and the nuclear DAMP HMGB1 was found in the cell cytoplasm. Furthermore, it was shown that NB-PDT induced the release of the DAMPs HSP70 and ATP, as well as the pro-inflammatory cytokines IL-1β and IL-6. Conditioned medium from high EGFR-expressing tumor cells treated with NB-PDT led to the maturation of human dendritic cells, as indicated by the upregulation of CD86 and MHC II on their cell surface, and the increased release of IL-12p40 and IL-1β. Subsequently, these dendritic cells induced CD4+ T cell proliferation, accompanied by IFNγ release. Altogether, the initial steps reported here point towards the potential of NB-PDT to stimulate the immune system, thus giving this selective-local therapy a systemic reach.Despite being a selective and controllable treatment against tumor cells, therapies known to be considerably aggressive towards all tissues (i.e., chemo-and radiotherapy) are still the mainstream clinical practice, when it comes to combat cancer [5]. Some current barriers for the establishment of PDT in routine practice are the required technology, complex dosimetry, limited tissue penetration of light and/or PS, lack of tumor specificity and prolonged skin photosensitivity [1,5]. Efforts have been put into improving the selectivity of PDT towards the cancer cells by using antibodies, an approach which is now in phase II clinical trial (NCT02422979) [6]. Conjugation of a water-soluble PS (IRDye700DX) to an antibody allows the PS to be specifically delivered to cancer cells overexpressing a certain antigen on the cell membrane. In this manner, two levels of specificity are established: the delivery of PS to target-expressing cells and the local application of light at the tumor site.Another strategy to render PDT more tumor-selective is nanobody-targeted PDT (NB-PDT), which also utilizes the near-infrared PS IRDye700DX. In this case, however, a nanobody is used to provide the first level of specificity [7,8]. NBs are the smallest binding domains found in nature (~15 kDa) and consist uniquely of the variable domain of heavy chain antibodies present in Camelids [9]. The use of a NB for PDT brings a ...

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Section: Introductionmentioning

confidence: 99%

The Potential of Nanobody-Targeted Photodynamic Therapy to Trigger Immune Responses

Hernández

Angelier

D’Ondes

et al. 2020

Cancers

Self Cite

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“…In this method, isolated cells from the patient are grown as organoids in a 3D matrix, rather than in more traditional 2D culture systems, which better represent in vivo tumor architecture and cell-cell interactions. It has been demonstrated that PDOs from HNC can recapitulate the morphologic and molecular characteristics of the original tumor [33,34]. In addition, PDOs can be readily used to test sensitivity to multiple drugs and radiation due to their relatively rapid 3D culture (i.e., days), compared to the lengthy process of establishing PDXs (i.e., weeks to months) [35].…”

Section: Organoid Modelsmentioning

confidence: 99%

Patient Derived Models to Study Head and Neck Cancer Radiation Response

Cosper

Abel

Lee

et al. 2020

Cancers

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Patient-derived model systems are important tools for studying novel anti-cancer therapies. Patient-derived xenografts (PDXs) have gained favor over the last 10 years as newer mouse strains have improved the success rate of establishing PDXs from patient biopsies. PDXs can be engrafted from head and neck cancer (HNC) samples across a wide range of cancer stages, retain the genetic features of their human source, and can be treated with both chemotherapy and radiation, allowing for clinically relevant studies. Not only do PDXs allow for the study of patient tissues in an in vivo model, they can also provide a renewable source of cancer cells for organoid cultures. Herein, we review the uses of HNC patient-derived models for radiation research, including approaches to establishing both orthotopic and heterotopic PDXs, approaches and potential pitfalls to delivering chemotherapy and radiation to these animal models, biological advantages and limitations, and alternatives to animal studies that still use patient-derived tissues.

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“…In this method, isolated cells from the patient are grown as organoids in a 3D matrix, rather than in more traditional 2D culture systems, which better represents in vivo tumor architecture and cell-cell interactions. It has been demonstrated that PDOs from HNC can recapitulate morphologic and molecular characteristics of the original tumor [28,29]. In addition, PDOs can be readily used to test sensitivity to multiple drugs and radiation due to relatively rapid 3D culture (i.e.…”

Section: Organoid Modelsmentioning

confidence: 99%

“…Humanized mouse models offer a potential solution to this problem as they are immunocompromised to allow for PDX growth, but are then engrafted with a partially functional "human" immune system allowing for the study of the immune response [36]. Humanized animal models offer the opportunity for investigators to study immunomodulatory agents in human cancers (28,(30)(31)(32), work that has taken on greater importance since the 2019 approval of pembrolizumab in the first-line setting for metastatic HNC patients.…”

Section: Humanized Modelsmentioning

confidence: 99%

Patient Derived Models to Study Head and Neck Cancer Radiation Response

Cosper¹,

Abel²,

Lee³

et al. 2020

Preprint

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Patient derived model systems are important tools for studying novel anti-cancer therapies. Patient derived xenografts (PDXs) have gained favor over the last 10 years as newer mouse strains have improved the success rate of establishing PDXs from patient biopsies. PDXs can be engrafted from head and neck cancer (HNC) samples across a wide range of cancer stages, retain the genetic features of their human source, and can be treated with both chemotherapy and radiation, allowing for clinically relevant studies. Not only do PDXs allow for study of patient tissues in an in vivo model, they can also provide a renewable source of cancer cells for organoid cultures. Herein, we review the uses of HNC patient derived models for radiation research including approaches to establishing both orthotopic and heterotopic PDXs, approaches and potential pitfalls to delivering chemotherapy and radiation to these animal models, biological advantages and limitations, and alternatives to animal studies that still use patient-derived tissues.

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Patient-Derived Head and Neck Cancer Organoids Recapitulate EGFR Expression Levels of Respective Tissues and Are Responsive to EGFR-Targeted Photodynamic Therapy

Cited by 78 publications

References 52 publications

The Potential of Nanobody-Targeted Photodynamic Therapy to Trigger Immune Responses

The Potential of Nanobody-Targeted Photodynamic Therapy to Trigger Immune Responses

Patient Derived Models to Study Head and Neck Cancer Radiation Response

Patient Derived Models to Study Head and Neck Cancer Radiation Response

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