The transduction pattern of IL‐12‐encoding lentiviral vectors shapes the immunological outcome

Goyvaerts, Cleo; Broos, Katrijn; Escors, David; Heirman, Carlo; Raes, Geert; Baetseĺier, Patrick De; Thielemans, Kris; Breckpot, Karine

doi:10.1002/eji.201545559

Cited by 14 publications

(13 citation statements)

References 47 publications

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“…Consequently, strategies need to be developed that exclusively act on TiDCs, preferably on CD8a þ TiDCs, which are critical for the stimulation of antitumor immunity (8,9). Several strategies have been developed to target adjuvants like TLR ligands or IL12, together with antigens, to cross-priming DCs (10)(11)(12)(13)(14)(15). Often these exploit antibodies or nanobodies to surface markers differentially expressed by DC subsets (13,15).…”

Section: Introductionmentioning

confidence: 99%

Intratumoral Delivery of TriMix mRNA Results in T-cell Activation by Cross-Presenting Dendritic Cells

Lint

Renmans

Broos

et al. 2016

Cancer Immunology Research

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100

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Section: Introductionmentioning

confidence: 99%

Intratumoral Delivery of TriMix mRNA Results in T-cell Activation by Cross-Presenting Dendritic Cells

Lint

Renmans

Broos

et al. 2016

Cancer Immunology Research

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100

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show abstract

“…Furthermore, the proinflammatory cytokines transiently released by DCs transduced with Vpx-vectors expressing CD40L reactivated latent HIV-1 provirus in latency models, supporting the use of such vectors in a two-pronged, “shock and kill” approach for reducing the latent reservoir and facilitating a functional cure ( 21 ). Goyvaerts et al similarly capitalized on the ability of IL-12 to enhance expansion CD4+ Th1 cells and cytotoxic effector cells and showed that DCs transduced with LV vectors expressing IL-12-enhanced antigen-specific CTLs in vivo ( 55 ). Others developed LV vectors expressing antigenic epitopes in tandem with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) or GM-CSF and IFN-α to enhance the longevity of transduced DCs and promote a more durable immune response ( 56 – 59 ).…”

Section: Strategies To Enhance LV Vector Immunogenicitymentioning

confidence: 99%

Recent Advances in Lentiviral Vaccines for HIV-1 Infection

Norton

Miller

2016

Front. Immunol.

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The development of an effective HIV vaccine to prevent and/or cure HIV remains a global health priority. Given their central role in the initiation of adaptive immune responses, dendritic cell (DC)-based vaccines are being increasingly explored as immunotherapeutic strategies to enhance HIV-specific T cells in infected individuals and, thus, promote immune responses that may help facilitate a functional cure. HIV-1-based lentiviral (LV) vectors have inherent advantages as DC vaccine vectors due to their ability to transduce non-dividing cells and integrate into the target cell genomic DNA, allowing for expression of encoded antigens over the lifespan of the cell. Moreover, LV vectors may express additional immunostimulatory and immunoregulatory proteins that enhance DC function and direct antigen-specific T cells responses. Recent basic and clinical research efforts have broadened our understanding of LV vectors as DC-based vaccines. In this review, we provide an overview of the pre-clinical and clinical LV vector vaccine studies for treating HIV to date. We also discuss advances in LV vector designs that have enhanced DC transduction efficiency, target cell specificity, and immunogenicity, and address potential safety concerns regarding LV vector-based vaccines.

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“…Interestingly, some of these studies highlight the CD28-CD80 costimulation signaling pathway as a major contributor to efficacious responses to ICI (Hui et al, 2017;Zuazo et al, 2019). Indeed, several studies show a key role for IL-12-expressing dendritic cells with cross-presentation capacities for good responses to immunotherapies (Kerkar et al, 2011;Goyvaerts et al, 2015;Berraondo et al, 2018;Garris et al, 2018;Etxeberria et al, 2019). These results reinforce the idea that a systemic functional immunity is very likely a required factor for the efficacy of immunotherapies.…”

Section: Tumor-extrinsic Factors and Resistance To Pd-l1/pd-1 Blockadmentioning

confidence: 62%

Resistance to PD-L1/PD-1 Blockade Immunotherapy. A Tumor-Intrinsic or Tumor-Extrinsic Phenomenon?

et al. 2020

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Cancer immunotherapies targeting immune checkpoints such as programmed cell-death protein 1 (PD-1) and its ligand programmed cell-death 1 ligand 1 (PD-L1), are revolutionizing cancer treatment and transforming the practice of medical oncology. However, despite all the recent successes of this type of immunotherapies, most patients are still refractory and present either intrinsic resistance or acquired resistance. Either way, this is a major clinical problem and one of the most significant challenges in oncology. Therefore, the identification of biomarkers to predict clinical responses or for patient stratification by probability of response has become a clinical necessity. However, the mechanisms leading to PD-L1/PD-1 blockade resistance are still poorly understood. A deeper understanding of the basic mechanisms underlying resistance to cancer immunotherapies will provide insight for further development of novel strategies designed to overcome resistance and treatment failure. Here we discuss some of the major molecular mechanisms of resistance to PD-L1/PD-1 immune checkpoint blockade and argue whether tumor intrinsic or extrinsic factors constitute main determinants of response and resistance.

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The transduction pattern of IL‐12‐encoding lentiviral vectors shapes the immunological outcome

Cited by 14 publications

References 47 publications

Intratumoral Delivery of TriMix mRNA Results in T-cell Activation by Cross-Presenting Dendritic Cells

Intratumoral Delivery of TriMix mRNA Results in T-cell Activation by Cross-Presenting Dendritic Cells

Recent Advances in Lentiviral Vaccines for HIV-1 Infection

Resistance to PD-L1/PD-1 Blockade Immunotherapy. A Tumor-Intrinsic or Tumor-Extrinsic Phenomenon?

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