Leveraging Endogenous Dendritic Cells to Enhance the Therapeutic Efficacy of Adoptive T-Cell Therapy and Checkpoint Blockade

Hübbe, Mie Linder; Jæhger, Ditte Elisabeth; Andresen, Thomas Lars; Andersen, Mads Hald

doi:10.3389/fimmu.2020.578349

Cited by 11 publications

(10 citation statements)

References 162 publications

(169 reference statements)

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“…Additionally, antigen presentation and activation of DCs in the tumor-draining lymph node played a role. Therefore, some antitumoral activity in the immunocompetent model could be seen, while the result was modest in immunodeficient models [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Systemic Delivery of Oncolytic Adenovirus to Tumors Using Tumor-Infiltrating Lymphocytes as Carriers

Santos

Heiniö

Quixabeira

et al. 2021

Cells

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Immunotherapy with tumor-infiltrating lymphocytes (TIL) or oncolytic adenoviruses, have shown promising results in cancer treatment, when used as separate therapies. When used in combination, the antitumor effect is synergistically potentiated due oncolytic adenovirus infection and its immune stimulating effects on T cells. Indeed, studies in hamsters have shown a 100% complete response rate when animals were treated with oncolytic adenovirus coding for TNFa and IL-2 (Ad5/3-E2F-D24-hTNFa-IRES-hIL2; TILT-123) and TIL therapy. In humans, one caveat with oncolytic virus therapy is that intratumoral injection has been traditionally preferred over systemic administration, for achieving sufficient virus concentrations in tumors, especially when neutralizing antibodies emerge. We have previously shown that 5/3 chimeric oncolytic adenovirus can bind to human lymphocytes for avoidance of neutralization. In this study, we hypothesized that incubation of oncolytic adenovirus (TILT-123) with TILs prior to systemic injection would allow delivery of virus to tumors. This approach would deliver both components in one self-amplifying product. TILs would help deliver TILT-123, whose replication will recruit more TILs and increase their cytotoxicity. In vitro, TILT-123 was seen binding efficiently to lymphocytes, supporting the idea of dual administration. We show in vivo in different models that virus could be delivered to tumors with TILs as carriers.

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Section: Discussionmentioning

confidence: 99%

Systemic Delivery of Oncolytic Adenovirus to Tumors Using Tumor-Infiltrating Lymphocytes as Carriers

Santos

Heiniö

Quixabeira

et al. 2021

Cells

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“…Low‐function DCs highly express antigen uptake receptors and show low expression of co‐stimulatory molecules and chemokines. 68 DC vaccines currently use cocktail therapy to cultivate mature DCs. CD14+ monocytes are initially isolated from peripheral blood mononuclear cells (PBMCs) in the patient and mix them with GM‐CSF and IL‐4 for 5–7 days to convert the monocytes into immature DC cells.…”

Section: Influence Of DC Vaccines On the Immune Mi...mentioning

confidence: 99%

Dendritic cell vaccines improve the glioma microenvironment: Influence, challenges, and future directions

Zhou

Jia

et al. 2022

Cancer Medicine

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Introduction Gliomas, especially the glioblastomas, are one of the most aggressive intracranial tumors with poor prognosis. This might be explained by the heterogeneity of tumor cells and the inhibitory immunological microenvironment. Dendritic cells (DCs), as the most potent in vivo functional antigen‐presenting cells, link innate immunity with adaptive immunity. However, their function is suppressed in gliomas. Therefore, overcoming the dysfunction of DCs in the TME might be critical to treat gliomas. Method In this paper we proposed the specificity of the glioma microenvironment, analyzed the pathways leading to the dysfunction of DCs in tumor microenvironment of patients with glioma, summarized influence of DC‐based immunotherapy on the tumor microenvironment and proposed new development directions and possible challenges of DC vaccines. Result DC vaccines can improve the immunosuppressive microenvironment of glioma patients. It will bring good treatment prospects to patients. We also proposed new development directions and possible challenges of DC vaccines, thus providing an integrated understanding of efficacy on DC vaccines for glioma treatment.

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“…DCs are popularly known as the immune system’s professional APCs and are paramount for initiating anti-tumor immune responses [ 28 ]. Harvesting the potential of DCs as a vaccine in cancer to prime T cells against tumor antigens is a long-standing concept.…”

Section: Immunotherapies In Ocmentioning

confidence: 99%

Dendritic Cell Vaccines: A Promising Approach in the Fight against Ovarian Cancer

Audhut

Deschoemaeker

Allonsius

et al. 2022

Cancers

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Ovarian cancer (OC) is the deadliest gynecological malignancy in developed countries and is the seventh-highest cause of death in women diagnosed with cancer worldwide. Currently, several therapies are in use against OC, including debulking surgery, chemotherapy, as well as targeted therapies. Even though the current standard-of-care therapies improve survival, a vast majority of OC patients relapse. Additionally, immunotherapies have only resulted in meager patient outcomes, potentially owing to the intricate immunosuppressive nexus within the tumor microenvironment. In this scenario, dendritic cell (DC) vaccination could serve as a potential addition to the therapeutic options available against OC. In this review, we provide an overview of current therapies in OC, focusing on immunotherapies. Next, we highlight the potential of using DC vaccines in OC by underscoring the different DC subsets and their functions in OC. Finally, we provide an overview of the advances and pitfalls of current DC vaccine strategies in OC while providing future perspectives that could improve patient outcomes.

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Leveraging Endogenous Dendritic Cells to Enhance the Therapeutic Efficacy of Adoptive T-Cell Therapy and Checkpoint Blockade

Cited by 11 publications

References 162 publications

Systemic Delivery of Oncolytic Adenovirus to Tumors Using Tumor-Infiltrating Lymphocytes as Carriers

Systemic Delivery of Oncolytic Adenovirus to Tumors Using Tumor-Infiltrating Lymphocytes as Carriers

Dendritic cell vaccines improve the glioma microenvironment: Influence, challenges, and future directions

Dendritic Cell Vaccines: A Promising Approach in the Fight against Ovarian Cancer

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