Trial watch: dendritic cell vaccination for cancer immunotherapy

Sprooten, Jenny; Ceusters, Jolien; Coosemans, An; Agostinis, Patrizia; Vleeschouwer, Steven De; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo; Garg, Abhishek D.

doi:10.1080/2162402x.2019.1638212

Cited by 121 publications

(118 citation statements)

References 385 publications

(429 reference statements)

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“…adoptive T cell therapies, cancer vaccines). [53][54][55][56][57][58][59] Notwithstanding the aforementioned limitations, our results delineate a strategy for tumor treatment that involves a therapy consisting in the administration of three drug classes: (i) ICD inducers exemplified by MTX and OXA, (ii) CRMs exemplified by HC and Spd and substitutable for fasting (if the nutritional status of the patient allows it) and (iii) ICIs targeting the PD-1/PD-L1 interaction. As shown here, such a triple combination has the potential to cure the majority of mice bearing established fibrosarcomas.…”

Section: Discussionmentioning

confidence: 91%

A synergistic triad of chemotherapy, immune checkpoint inhibitors, and caloric restriction mimetics eradicates tumors in mice

et al. 2019

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We have recently shown that chemotherapy with immunogenic cell death (ICD)-inducing agents can be advantageously combined with fasting regimens or caloric restriction mimetics (CRMs) to achieve superior tumor growth control via a T cell-dependent mechanism. Here, we show that the blockade of the CD11b-dependent extravasation of myeloid cells blocks such a combination effect as well. Based on the characterization of the myeloid and lymphoid immune infiltrates, including the expression pattern of immune checkpoint proteins (and noting a chemotherapy-induced overexpression of programmed death-ligand 1, PD-L1, on both cancer cells and leukocytes, as well as a reduced frequency of exhausted CD8 + T cells positive for programmed cell death 1 protein, PD-1), we then evaluated the possibility to combine ICD inducers, CRMs and targeting of the PD-1/PD-L1 interaction. While fasting or CRMs failed to improve tumor growth control by PD-1 blockade, ICD inducers alone achieved a partial sensitization to treatment with a PD-1-specific antibody. However, definitive cure of most of the tumorbearing mice was only achieved by a tritherapy combining (i) ICD inducers exemplified by mitoxantrone and oxaliplatin, (ii) CRMs exemplified by hydroxycitrate and spermidine and substitutable for by fasting, and (iii) immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 interaction. Altogether, these results point to the possibility of synergistic interactions among distinct classes of anticancer agents. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 91%

A synergistic triad of chemotherapy, immune checkpoint inhibitors, and caloric restriction mimetics eradicates tumors in mice

et al. 2019

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“…The simultaneous utilization of complementary approaches would enhance the clinical response by covering the deficiencies of each alone. Clinical trials are already underway to assess DC-based vaccination within a landscape of such combinatorial approaches to cancer treatment [32].…”

Section: Pros/consmentioning

confidence: 99%

“…Clinical trials with the purpose of investigating the efficacy and safety of the combinatorial approach, including the simultaneous application of anticancer vaccine and ICI, are already being undertaken [32].…”

Section: Introductionmentioning

confidence: 99%

Dendritic Cells in Anticancer Vaccination: Rationale for Ex Vivo Loading or In Vivo Targeting

Baldin

Savvateeva

Bazhin

et al. 2020

Cancers

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Dendritic cells (DCs) have shown great potential as a component or target in the landscape of cancer immunotherapy. Different in vivo and ex vivo strategies of DC vaccine generation with different outcomes have been proposed. Numerous clinical trials have demonstrated their efficacy and safety in cancer patients. However, there is no consensus regarding which DC-based vaccine generation method is preferable. A problem of result comparison between trials in which different DC-loading or -targeting approaches have been applied remains. The employment of different DC generation and maturation methods, antigens and administration routes from trial to trial also limits the objective comparison of DC vaccines. In the present review, we discuss different methods of DC vaccine generation. We conclude that standardized trial designs, treatment settings and outcome assessment criteria will help to determine which DC vaccine generation approach should be applied in certain cancer cases. This will result in a reduction in alternatives in the selection of preferable DC-based vaccine tactics in patient. Moreover, it has become clear that the application of a DC vaccine alone is not sufficient and combination immunotherapy with recent advances, such as immune checkpoint inhibitors, should be employed to achieve a better clinical response and outcome.

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“…12,24,57,113,119,224,237 Ultimately, APCs engulfing TAAs or TSAs and receiving these immunostimulatory cues acquire an extraordinary ability to crosspresent TAA-or TSA-derived epitopes to CD4 + and/or CD8 + T cells in the context of co-stimulation, which enables TAA/TSAtargeting immunity. [239][240][241][242][243][244] In multiple oncological settings, cancer cells capable of undergoing ICD in response to microenvironmental or therapeutic stress are subjected to increased immunological pressure, 245 resulting in the selection of poorly immunogenic tumor variants displaying: (1) reduced antigenicity (due to TAA/TSA loss or defects in MHC Class I exposure); [246][247][248][249][250][251][252][253] (2) genetic or epigenetic annihilation of the intracellular stress pathways that support the emission of ICD-associated DAMPs, cytokines or chemokines; 254 and/or (3) direct genetic or epigenetic silencing of specific DAMPs (e.g. CALR) or type I IFN.…”

Section: Introductionmentioning

confidence: 99%

Trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology

et al. 2020

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The term 'immunogenic cell death' (ICD) denotes an immunologically unique type of regulated cell death that enables, rather than suppresses, T cell-driven immune responses that are specific for antigens derived from the dying cells. The ability of ICD to elicit adaptive immunity heavily relies on the immunogenicity of dying cells, implying that such cells must encode and present antigens not covered by central tolerance (antigenicity), and deliver immunostimulatory molecules such as damage-associated molecular patterns and cytokines (adjuvanticity). Moreover, the host immune system must be equipped to detect the antigenicity and adjuvanticity of dying cells. As cancer (but not normal) cells express several antigens not covered by central tolerance, they can be driven into ICD by some therapeutic agents, including (but not limited to) chemotherapeutics of the anthracycline family, oxaliplatin and bortezomib, as well as radiation therapy. In this Trial Watch, we describe current trends in the preclinical and clinical development of ICD-eliciting chemotherapy as partner for immunotherapy, with a focus on trials assessing efficacy in the context of immunomonitoring.

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Trial watch: dendritic cell vaccination for cancer immunotherapy

Cited by 121 publications

References 385 publications

A synergistic triad of chemotherapy, immune checkpoint inhibitors, and caloric restriction mimetics eradicates tumors in mice

A synergistic triad of chemotherapy, immune checkpoint inhibitors, and caloric restriction mimetics eradicates tumors in mice

Dendritic Cells in Anticancer Vaccination: Rationale for Ex Vivo Loading or In Vivo Targeting

Trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology

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