Dendritic cell vaccines for high-grade gliomas

Eagles, Matthew E; Nassiri, Farshad; Badhiwala, Jetan H.; Suppiah, Suganth; Almenawer, Saleh A.; Zadeh, Gelareh; Aldape, Kenneth

doi:10.2147/tcrm.s135865

Cited by 49 publications

(36 citation statements)

References 87 publications

(127 reference statements)

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“…It is important to further investigate this in the future to improve response rates of patients to immunotherapy and to find new strategies against BrM by exploiting the full potential of T cell immunity in this context. Using DC vaccines to boost T cell responses is only one of many potential treatment possibilities, which could be explored in this context and is under current investigation in brain tumors (156). Another strategy of applying T cells for BrM treatment is the delivery of genetically engineered CAR T cells directed against known tumor antigens, which led to reduced tumor growth in a xenograft mouse model (157).…”

Section: Introductionmentioning

confidence: 99%

Microenvironmental Regulation of Tumor Progression and Therapeutic Response in Brain Metastasis

et al. 2019

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Cellular and non-cellular components of the tumor microenvironment (TME) are emerging as key regulators of primary tumor progression, organ-specific metastasis, and therapeutic response. In the era of TME-targeted- and immunotherapies, cancer-associated inflammation has gained increasing attention. In this regard, the brain represents a unique and highly specialized organ. It has long been regarded as an immunological sanctuary site where the presence of the blood brain barrier (BBB) and blood cerebrospinal fluid barrier (BCB) restricts the entry of immune cells from the periphery. Consequently, tumor cells that metastasize to the brain were thought to be shielded from systemic immune surveillance and destruction. However, the detailed characterization of the immune landscape within border-associated areas of the central nervous system (CNS), such as the meninges and the choroid plexus, as well as the discovery of lymphatics and channels that connect the CNS with the periphery, have recently challenged the dogma of the immune privileged status of the brain. Moreover, the presence of brain metastases (BrM) disrupts the integrity of the BBB and BCB. Indeed, BrM induce the recruitment of different immune cells from the myeloid and lymphoid lineage to the CNS. Blood-borne immune cells together with brain-resident cell-types, such as astrocytes, microglia, and neurons, form a highly complex and dynamic TME that affects tumor cell survival and modulates the mode of immune responses that are elicited by brain metastatic tumor cells. In this review, we will summarize recent findings on heterotypic interactions within the brain metastatic TME and highlight specific functions of brain-resident and recruited cells at different rate-limiting steps of the metastatic cascade. Based on the insight from recent studies, we will discuss new opportunities and challenges for TME-targeted and immunotherapies for BrM.

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Section: Introductionmentioning

confidence: 99%

Microenvironmental Regulation of Tumor Progression and Therapeutic Response in Brain Metastasis

et al. 2019

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“…124 For example, the combination of dendritic cell-targeted vaccines with nanoparticles loaded with anticancer drugs should lead to a superior anticancer activity. 125 Combination with nanocarrier loaded with checkpoint inhibitors could be another valuable therapeutic approach. 126 Furthermore, neutrophils (NE) have a native ability to traverse BBB/BBTB and penetrate the glioma site, where the tumour associated NE favour the continuous recruitment of circulating NE; in addition, local brain inflammation, following surgical tumour removal, activates NE migration towards to the inflamed brain.…”

Section: Nanocarrier-mediated Cell Therapymentioning

confidence: 99%

<p>Overcoming the Blood–Brain Barrier: Successes and Challenges in Developing Nanoparticle-Mediated Drug Delivery Systems for the Treatment of Brain Tumours</p>

Ferraris¹,

Cavalli²,

Panciani³

et al. 2020

IJN

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High-grade gliomas are still characterized by a poor prognosis, despite recent advances in surgical treatment. Chemotherapy is currently practiced after surgery, but its efficacy is limited by aspecific toxicity on healthy cells, tumour cell chemoresistance, poor selectivity, and especially by the blood-brain barrier (BBB). Thus, despite the large number of potential drug candidates, the choice of effective chemotherapeutics is still limited to few compounds. Malignant gliomas are characterized by high infiltration and neovascularization, and leaky BBB (the so-called blood-brain tumour barrier); surgical resection is often incomplete, leaving residual cells that are able to migrate and proliferate. Nanocarriers can favour delivery of chemotherapeutics to brain tumours owing to different strategies, including chemical stabilization of the drug in the bloodstream; passive targeting (because of the leaky vascularization at the tumour site); inhibition of drug efflux mechanisms in endothelial and cancer cells; and active targeting by exploiting carriers and receptors overexpressed at the blood-brain tumour barrier. Within this concern, a suitable nanomedicine-based therapy for gliomas should not be limited to cytotoxic agents, but also target the most important pathogenetic mechanisms, including cell differentiation pathways and angiogenesis. Moreover, the combinatorial approach of cell therapy plus nanomedicine strategies can open new therapeutical opportunities. The major part of attempted preclinical approaches on animal models involves active targeting with protein ligands, but, despite encouraging results, a few number of nanomedicines reached clinical trials, and most of them include drug-loaded nanocarriers free of targeting ligands, also because of safety and scalability concerns.

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“…These ACT attributes led to the FDA approval of sipuleucel-T (in 2010), which is a DC vaccine that is used for the treatment of asymptomatic or minimally symptomatic castration-resistant prostate cancer [ 151 , 152 ]. Sipuleucel-T is able to activate autologous anti-tumor immune reactions toward prostate tumors overexpressing prostatic acid phosphatase tumor antigens [ 151 , 153 , 154 ]. This DC-based vaccine (sipuleucel-T) achieved high objective response rates in melanoma patients (8–15%), which were characterized by an improved overall survival (20%) mediated through a robust CTL and natural killer cell (NK)-dependent immune response [ 155 , 156 , 157 ].…”

Section: Introductionmentioning

confidence: 99%

“…Tumor-infiltrating lymphocytes (TILs) are another form of ACT introduced in 1988 to treat melanoma patients [ 41 , 54 , 158 ]. This therapeutic approach consists of isolating TILs from the patient’s tumor and expanding them ex vivo using interleukin-2 (IL-2) activation, before re-injection into the autologous patient to induce a CTL-dependent immune response [ 54 , 154 , 159 ]. This treatment was validated by multiple clinical trials confirming the overall objective responses of 49–72% with long-term remissions of >5 years in treated melanoma patients [ 108 , 109 , 110 ].…”

Section: Introductionmentioning

confidence: 99%

Antibody-Based Immunotherapy: Alternative Approaches for the Treatment of Metastatic Melanoma

et al. 2020

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Melanoma is the least common form of skin cancer and is associated with the highest mortality. Where melanoma is mostly unresponsive to conventional therapies (e.g., chemotherapy), BRAF inhibitor treatment has shown improved therapeutic outcomes. Photodynamic therapy (PDT) relies on a light-activated compound to produce death-inducing amounts of reactive oxygen species (ROS). Their capacity to selectively accumulate in tumor cells has been confirmed in melanoma treatment with some encouraging results. However, this treatment approach has not reached clinical fruition for melanoma due to major limitations associated with the development of resistance and subsequent side effects. These adverse effects might be bypassed by immunotherapy in the form of antibody–drug conjugates (ADCs) relying on the ability of monoclonal antibodies (mAbs) to target specific tumor-associated antigens (TAAs) and to be used as carriers to specifically deliver cytotoxic warheads into corresponding tumor cells. Of late, the continued refinement of ADC therapeutic efficacy has given rise to photoimmunotherapy (PIT) (a light-sensitive compound conjugated to mAbs), which by virtue of requiring light activation only exerts its toxic effect on light-irradiated cells. As such, this review aims to highlight the potential clinical benefits of various armed antibody-based immunotherapies, including PDT, as alternative approaches for the treatment of metastatic melanoma.

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Dendritic cell vaccines for high-grade gliomas

Cited by 49 publications

References 87 publications

Microenvironmental Regulation of Tumor Progression and Therapeutic Response in Brain Metastasis

Microenvironmental Regulation of Tumor Progression and Therapeutic Response in Brain Metastasis

<p>Overcoming the Blood–Brain Barrier: Successes and Challenges in Developing Nanoparticle-Mediated Drug Delivery Systems for the Treatment of Brain Tumours</p>

Antibody-Based Immunotherapy: Alternative Approaches for the Treatment of Metastatic Melanoma

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