Tilsotolimod: an investigational synthetic toll-like receptor 9 (TLR9) agonist for the treatment of refractory solid tumors and melanoma

Karime, Christian; Wang, Jing; Woodhead, Gregory; Mody, Kabir; Hennemeyer, Charles; Borad, Mitesh J.; Mahadevan, Daruka; Chandana, Sreenivasa R; Babiker, Hani M.

doi:10.1080/13543784.2022.2019706

Cited by 8 publications

(3 citation statements)

References 87 publications

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“…The most common agonists that control myeloid cell phenotypes are ligands binding TLR3, 4 and 7–9. For example, in solid tumors, it has been found that TLR9 agonists, e.g., CpG oligodeoxynucleotide DNA, increased the number of tumor-infiltrating lymphocytes in the TME, while MDSCs, TAMs, and Treg cells were reduced [ 120 , 121 ]. TRL9 agonists are now in clinical trials for melanoma and colorectal cancer (NCT03618641, NCT03507699).…”

Section: Immunotherapies Targeting the Innate Immune System In Amlmentioning

confidence: 99%

Targeting the innate immune system in pediatric and adult AML

Perzolli,

Koedijk,

Zwaan

et al. 2024

Leukemia

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While the introduction of T cell-based immunotherapies has improved outcomes in many cancer types, the development of immunotherapies for both adult and pediatric AML has been relatively slow and limited. In addition to the need to identify suitable target antigens, a better understanding of the immunosuppressive tumor microenvironment is necessary for the design of novel immunotherapy approaches. To date, most immune characterization studies in AML have focused on T cells, while innate immune lineages such as monocytes, granulocytes and natural killer (NK) cells, received less attention. In solid cancers, studies have shown that innate immune cells, such as macrophages, myeloid-derived suppressor cells and neutrophils are highly plastic and may differentiate into immunosuppressive cells depending on signals received in their microenvironment, while NK cells appear to be functionally impaired. Hence, an in-depth characterization of the innate immune compartment in the TME is urgently needed to guide the development of immunotherapeutic interventions for AML. In this review, we summarize the current knowledge on the innate immune compartment in AML, and we discuss how targeting its components may enhance T cell-based- and other immunotherapeutic approaches.

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Section: Immunotherapies Targeting the Innate Immune System In Amlmentioning

confidence: 99%

Targeting the innate immune system in pediatric and adult AML

Perzolli,

Koedijk,

Zwaan

et al. 2024

Leukemia

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“…In the future, direct injection of alternative immune-stimulating agents into HCCs may be used to augment locoregional or systemic approaches. Toll-like receptor 9 (TLR9) agonists (CpG) have been developed to stimulate the innate arm of the immune system [103]. Recently, phase I dose escalation trials involving the intratumoral injection of CpG into refractory visceral solid tumors alone or in combination with ipilimumab demonstrated promising results [104,105].…”

Section: Other Immune-activating Therapiesmentioning

confidence: 99%

Friend or Foe? Locoregional Therapies and Immunotherapies in the Current Hepatocellular Treatment Landscape

Young

Hannallah

Goldberg

et al. 2023

IJMS

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Over the last several decades, a number of new treatment options for patients with hepatocellular carcinoma (HCC) have been developed. While treatment decisions for some patients remain clear cut, a large numbers of patients have multiple treatment options, and it can be hard for multidisciplinary teams to come to unanimous decisions on which treatment strategy or sequence of treatments is best. This article reviews the available data with regard to two treatment strategies, immunotherapies and locoregional therapies, with a focus on the potential of locoregional therapies to be combined with checkpoint inhibitors to improve outcomes in patients with locally advanced HCC. In this review, the available data on the immunomodulatory effects of locoregional therapies is discussed along with available clinical data on outcomes when the two strategies are combined.

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“…For instance, recent studies have proved that Viautolimod could help maintain persistent responses when combined with pembrolizumab in melanoma patients [ 111 , 112 , 113 ]. The durable performance of Lefitolimod was also found in combination therapy with ipilimumab against drug resistance [ 114 ], and so as for Tilsotolimod [ 115 ]. In addition, studies have demonstrated that several miRNAs, such as miR-17~92 families, miR-126, and miR-223, are involved in the activation and signaling pathway of TLR-9 receptors [ 116 , 117 , 118 ].…”

Section: Cutaneous Melanomamentioning

confidence: 99%

The Roles of MiRNAs (MicroRNAs) in Melanoma Immunotherapy

Dong

Tian

Zhao

et al. 2022

IJMS

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Melanoma is the most aggressive form of skin cancer, characterized by life-threatening and rapidly spreading progression. Traditional targeted therapy can alleviate tumors by inactivating hyperactive kinases such as BRAF or MEK but inevitably encounters drug resistance. The advent of immunotherapy has revolutionized melanoma treatment and significantly improved the prognosis of melanoma patients. MicroRNAs (miRNAs) are intricately involved in innate and adaptive immunity and are implicated in melanoma immunotherapy. This systematic review describes the roles of miRNAs in regulating the functions of immune cells in skin and melanoma, as well as the involvement of miRNAs in pharmacology including the effect, resistance and immune-related adverse events of checkpoint inhibitors such as PD-1 and CTLA-4 inhibitors, which are used for treating cutaneous, uveal and mucosal melanoma. The expressions and functions of miRNAs in immunotherapy employing tumor-infiltrating lymphocytes and Toll-like receptor 9 agonists are also discussed. The prospect of innovative therapeutic strategies such as the combined administration of miRNAs and immune checkpoint inhibitors and the nanotechnology-based delivery of miRNAs are also provided. A comprehensive understanding of the interplay between miRNAs and immunotherapy is crucial for the discovery of reliable biomarkers and for the development of novel miRNA-based therapeutics against melanoma.

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Tilsotolimod: an investigational synthetic toll-like receptor 9 (TLR9) agonist for the treatment of refractory solid tumors and melanoma

Cited by 8 publications

References 87 publications

Targeting the innate immune system in pediatric and adult AML

Targeting the innate immune system in pediatric and adult AML

Friend or Foe? Locoregional Therapies and Immunotherapies in the Current Hepatocellular Treatment Landscape

The Roles of MiRNAs (MicroRNAs) in Melanoma Immunotherapy

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