TCR-Directed Therapy in the Treatment of Metastatic Uveal Melanoma

Strobel, Stefanie; Machiraju, Devayani; Hassel, Jessica C.

doi:10.3390/cancers14051215

Cited by 11 publications

(5 citation statements)

References 50 publications

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“…157 Taking use of the intrinsic TCR-pMHC-dependent activation pathways, TCR-T offers a promising strategy to overcome the limitation of specific antigens in tumor treatments. 158 In addition to T cells, there has been ongoing development of alternative engineered immune cells, such as CAR-NK (natural killer cells) and CAR-M (macrophages), for cancer therapy.…”

Section: Fna-facilitated Specific Killing Of Cancer Cellsmentioning

confidence: 99%

“…In addition to CAR-T, TCR-T represents another typical type of immunotherapy that employs genetically modified T cells with engineered TCRs to target and kill cancer cells . Taking use of the intrinsic TCR-pMHC-dependent activation pathways, TCR-T offers a promising strategy to overcome the limitation of specific antigens in tumor treatments . In addition to T cells, there has been ongoing development of alternative engineered immune cells, such as CAR-NK (natural killer cells) and CAR-M (macrophages), for cancer therapy.…”

Section: Fna-facilitated Specific Killing Of Cancer Cellsmentioning

confidence: 99%

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Functional Nucleic Acid-Based Immunomodulation for T Cell-Mediated Cancer Therapy

Wu,

Lin,

Ling

et al. 2023

ACS Nano

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T cell-mediated immunity plays a pivotal role in cancer immunotherapy. The anticancer actions of T cells are coordinated by a sequence of biological processes, including the capture and presentation of antigens by antigen-presenting cells (APCs), the activation of T cells by APCs, and the subsequent killing of cancer cells by activated T cells. However, cancer cells have various means to evade immune responses. Meanwhile, these vulnerabilities provide potential targets for cancer treatments. Functional nucleic acids (FNAs) make up a class of synthetic nucleic acids with specific biological functions. With their diverse functionality, good biocompatibility, and high programmability, FNAs have attracted widespread interest in cancer immunotherapy. This Review focuses on recent research progress in employing FNAs as molecular tools for T cell-mediated cancer immunotherapy, including corresponding challenges and prospects.

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Section: Fna-facilitated Specific Killing Of Cancer Cellsmentioning

confidence: 99%

Section: Fna-facilitated Specific Killing Of Cancer Cellsmentioning

confidence: 99%

Functional Nucleic Acid-Based Immunomodulation for T Cell-Mediated Cancer Therapy

Wu,

Lin,

Ling

et al. 2023

ACS Nano

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“…They can be derived from TILs isolated from tumor biopsies of patients with UM and can be engineered to target certain antigens [88]. Strobel et al [117] have comprehensively reviewed this treatment option and thus, we briefly described it in this chapter. Additionally, we added some novel ongoing trials.…”

Section: Adoptive Cell Transfermentioning

confidence: 99%

Recent Advances and Challenges in Uveal Melanoma Immunotherapy

Xiao

Mao

2022

Cancers

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Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Compared to cutaneous melanoma (CM), which mainly harbors BRAF or NRAS mutations, UM predominantly harbors GNAQ or GNA11 mutations. Although primary UM can be controlled locally, approximately 50% of patients still develop metastases. To date, there have been no standard therapeutic strategies for the prevention or treatment of metastases. Unfortunately, chemotherapy and targeted therapies only induce minimal responses in patients with metastatic UM, with a median survival time of only 4–5 months after metastasis detection. Immunotherapy agents, such as immune checkpoint inhibitors, have achieved pioneering outcomes in CM but have shown limited effects in UM. Researchers have explored several feasible checkpoints to identify options for future therapies. Cancer vaccines have shown little in the way of therapeutic benefit in patients with UM, and there are few ongoing trials providing favorable evidence, but adoptive cell transfer-related therapies seem promising and deserve further investigation. More recently, the immune-mobilizing monoclonal T-cell receptor against the cancer molecule tebentafusp showed impressive antitumor effects. Meanwhile, oncolytic viruses and small molecule inhibitors have also gained ground. This review highlights recent progress in burgeoning treatments and provides innovative insights on feasible strategies for the treatment of UM.

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“…In recent years, signi cant progress has been made in early detection and multimodal therapeutic strategies, such as adoptive T-cell therapy and immune checkpoint inhibitors, leading to advancements in the management of UVM. However, the survival bene ts for patients remain limited 4 . Moreover, the prognosis of UVM patients continues to be poor due to the presence of high tumor heterogeneity 5 .…”

Section: Introductionmentioning

confidence: 99%

Machine Learning-based Classifier to Decipher Immune Landscape of Uveal Melanoma and Predict Patient Outcomes

Zhang,

Shen,

Jiang

et al. 2023

Preprint

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Uveal melanoma (UVM) is influenced by immune infiltration features, making the analysis of UVM genomic and immune signatures crucial for predicting patient prognosis and identifying potential targeted therapies.To address this issue, we leveraged multi-omics data from The Cancer Genome Atlas and GEO datasets, especially immune infiltration data, to classify UVM into distinct immune-related subgroups using an unsupervised clustering algorithm. The resulting subgroups were denoted as uveal melanoma carcinoma subtype 1 (UMCS1) and subtype 2 (UMCS2). We further examined differences in the immune microenvironment, immunotherapy response, and tumor metabolic pathways between these subgroups, aiming to identify targets related to immune infiltration. Additionally, we devised a risk scoring system based on subtype-specific markers to forecast the prognosis of UVM patients. Performance evaluation of the risk scoring system was conducted using receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and calibration curves.Our analysis successfully identified two distinct subtypes of UVM patients, characterized by genomic mutations and disparities in the immune environment. These subtypes exhibited diverse clinical features and biological processes. The aggressive subtype, UMCS2, presented a higher TNM stage and poorer patient survival. UMCS2 was distinguished by elevated metabolism and increased immune infiltration. However, UMCS2 also demonstrated a higher tumor mutational burden and immune dysfunction, resulting in diminished responsiveness to immunotherapy. Notably, the two subgroups exhibited differential sensitivity to targeted drugs due to substantial variances in metabolic and immune environments, with UMCS2 displaying lower sensitivity. Finally, we developed a risk scoring system utilizing subtype-specific biomarkers and assessed its diagnostic performance for UVM patients, achieving satisfactory results through ROC curves, decision curve analysis, and calibration curves. Our findings suggest that the remodeled immunometabolic pathways and the immune microenvironment contribute to the relatively low sensitivity of UVM to immunotherapy. Targeting these mutated pathways and immune infiltrating molecules may potentially address the current treatment dilemma in UVM. Moreover, the newly developed risk assessment system not only aids in predicting patient prognosis but also facilitates the identification of suitable populations for combination therapy.

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TCR-Directed Therapy in the Treatment of Metastatic Uveal Melanoma

Cited by 11 publications

References 50 publications

Functional Nucleic Acid-Based Immunomodulation for T Cell-Mediated Cancer Therapy

Functional Nucleic Acid-Based Immunomodulation for T Cell-Mediated Cancer Therapy

Recent Advances and Challenges in Uveal Melanoma Immunotherapy

Machine Learning-based Classifier to Decipher Immune Landscape of Uveal Melanoma and Predict Patient Outcomes

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