Poly-ICLC, a multi-functional immune modulator for treating cancer

Sultan, Hussein; Salazar, Andrés M.; Celis, Esteban

doi:10.1016/j.smim.2020.101414

Cited by 55 publications

(42 citation statements)

References 56 publications

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“…For instance, the TLR7 agonist, Imiquimod, induces a robust rejection of skin primary malignancies and metastases by generating a pro-inflammatory tumor microenvironment in human patients (164) (Table 1). Similarly, polyinosinicpolycytidylic acid (poly-IC), a TLR3 agonist, triggers T cell tumor infiltration and Th1 responses, which should in turn activate macrophages through IFNg signaling, to reduce malignant growth (165). Finally, the TLR9 agonist family CpG oligodeoxynucleotides (CpG ODN) have also shown strong cancer cytotoxic effects by exerting a potent tumor-localized immunostimulatory action (166) (Table 1).…”

Section: Pro-inflammatory Stimulation Via Tlr Agonismmentioning

confidence: 99%

Mechanisms of Macrophage Plasticity in the Tumor Environment: Manipulating Activation State to Improve Outcomes

et al. 2021

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Macrophages are a specialized class of innate immune cells with multifaceted roles in modulation of the inflammatory response, homeostasis, and wound healing. While developmentally derived or originating from circulating monocytes, naïve macrophages can adopt a spectrum of context-dependent activation states ranging from pro-inflammatory (classically activated, M1) to pro-wound healing (alternatively activated, M2). Tumors are known to exploit macrophage polarization states to foster a tumor-permissive milieu, particularly by skewing macrophages toward a pro-tumor (M2) phenotype. These pro-tumoral macrophages can support cancer progression by several mechanisms including immune suppression, growth factor production, promotion of angiogenesis and tissue remodeling. By preventing the adoption of this pro-tumor phenotype or reprogramming these macrophages to a more pro-inflammatory state, it may be possible to inhibit tumor growth. Here, we describe types of tumor-derived signaling that facilitate macrophage reprogramming, including paracrine signaling and activation of innate immune checkpoints. We also describe intervention strategies targeting macrophage plasticity to limit disease progression and address their implications in cancer chemo- and immunotherapy.

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Section: Pro-inflammatory Stimulation Via Tlr Agonismmentioning

confidence: 99%

Mechanisms of Macrophage Plasticity in the Tumor Environment: Manipulating Activation State to Improve Outcomes

et al. 2021

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“…The prototypical TLR3 agonist polyinosinic-polycytidylic acid (poly-IC) and its derivatives are being evaluated as intratumor interventions in advanced oncological indications. 160 For instance, poly-IC complexed with poly-L-lysine and carboxymethylcellulose (poly-ICLC/Hiltonol) is under investigation in B-cell lymphoma in association with radiotherapy and recombinant human FMS-like tyrosine kinase-3 ligand (Flt3L) (NCT01976585), and in mesothelioma in a neoadjuvant setting (NCT04525859) ( Table 2 ). Already, i.t .…”

Section: Prr Agonistsmentioning

confidence: 99%

Trial watch: intratumoral immunotherapy

et al. 2021

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While chemotherapy and radiotherapy remain the first-line approaches for the management of most unresectable tumors, immunotherapy has emerged in the past two decades as a game-changing treatment, notably with the clinical success of immune checkpoint inhibitors. Immunotherapies aim at (re)activating anticancer immune responses which occur in two main steps: (1) the activation and expansion of tumor-specific T cells following cross-presentation of tumor antigens by specialized myeloid cells (priming phase); and (2) the immunological clearance of malignant cells by these antitumor T lymphocytes (effector phase). Therapeutic vaccines, adjuvants, monoclonal antibodies, cytokines, immunogenic cell death-inducing agents including oncolytic viruses, anthracycline-based chemotherapy and radiotherapy, as well as adoptive cell transfer, all act at different levels of this cascade to (re)instate cancer immunosurveillance. Intratumoral delivery of these immunotherapeutics is being tested in clinical trials to promote superior antitumor immune activity in the context of limited systemic toxicity.

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“…By stimulating MDA5, Poly-ICLC potently induces IFN-I and IL-15. It can also promote T-cell expansion and enhance T-cell infiltration, making it a potent adjuvant for peptide cancer vaccines [ 43 ]. In recent years, several major clinical trials have tested the efficacy of peptide cancer vaccines.…”

Section: Introductionmentioning

confidence: 99%

Targeting neoantigens for cancer immunotherapy

Zhao

Pan²,

Wang³

et al. 2021

Biomark Res

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Neoantigens, a type of tumor-specific antigens derived from non-synonymous mutations, have recently been characterized as attractive targets for cancer immunotherapy. Owing to the development of next-generation sequencing and utilization of machine-learning algorithms, it has become feasible to computationally predict neoantigens by depicting genetic alterations, aberrant post-transcriptional mRNA processing and abnormal mRNA translation events within tumor tissues. Consequently, neoantigen-based therapies such as cancer vaccines have been widely tested in clinical trials and have demonstrated promising safety and efficacy, opening a new era for cancer immunotherapy. We systematically summarize recent advances in the identification of both personalized and public neoantigens, neoantigen formulations and neoantigen-based clinical trials in this review. Moreover, we discuss future techniques and strategies for neoantigen-based cancer treatment either as a monotherapy or as a combination therapy with radiotherapy, chemotherapy or immune checkpoint inhibitors.

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Poly-ICLC, a multi-functional immune modulator for treating cancer

Cited by 55 publications

References 56 publications

Mechanisms of Macrophage Plasticity in the Tumor Environment: Manipulating Activation State to Improve Outcomes

Mechanisms of Macrophage Plasticity in the Tumor Environment: Manipulating Activation State to Improve Outcomes

Trial watch: intratumoral immunotherapy

Targeting neoantigens for cancer immunotherapy

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