Cancer Therapy Targeting CD47/SIRPα

In the past decade, the field of cancer immunotherapy has rapidly advanced, establishing a crucial role for immune checkpoint blockers in the treatment of a variety of cancer types. In parallel with these remarkable clinical developments, further efforts have focused on ways of unleashing adaptive immune responses against cancer. CD47, a cell surface molecule overexpressed by several cancer types that facilitates immune escape from macrophages, dendritic cells and natural killer cells, and its ligand SIRPα, have emerged as potential therapeutic targets. A number of agents directed to CD47/SIRPα have been developed and demonstrated preclinical activity. Early phase clinical trials are investigating CD47/SIRPα directed agents with available data, suggesting safety and preliminary activity. Herein, we provide an overview of the mechanistic rationale of targeting CD47/SIRPα axis and associated clinical evidence.

Emerging Therapeutic Agents for Colorectal Cancer

There are promising new therapeutic agents for CRC patients, including novel small-molecule inhibitors and immune checkpoint blockers. We focused on emerging CRC’s therapeutic agents that have shown the potential for progress in clinical practice. This review provides an overview of tyrosine kinase inhibitors targeting VEGF and KIT, BRAF and MEK inhibitors, TLR9 agonist, STAT3 inhibitors, and immune checkpoint blockers (PD1/PDL-1 inhibitors), for which recent advances have been reported. These new agents have the potential to provide benefits to CRC patients with unmet medical needs.

miRNAs in the Regulation of Cancer Immune Response: Effect of miRNAs on Cancer Immunotherapy

In the last few decades, carcinogenesis has been extensively explored and substantial research has identified immunogenic involvement in various types of cancers. As a result, immune checkpoint blockers and other immune-based therapies were developed as novel immunotherapeutic strategies. However, despite being a promising therapeutic option, immunotherapy has significant constraints such as a high cost of treatment, unpredictable toxicity, and clinical outcomes. miRNAs are non-coding, small RNAs actively involved in modulating the immune system’s multiple signalling pathways by binding to the 3′-UTR of target genes. miRNAs possess a unique advantage in modulating multiple targets of either the same or different signalling pathways. Therefore, miRNA follows a ‘one drug multiple target’ hypothesis. Attempts are made to explore the therapeutic promise of miRNAs in cancer so that it can be transported from bench to bedside for successful immunotherapeutic results. Therefore, in the current manuscript, we discussed, in detail, the mechanism and role of miRNAs in different types of cancers relating to the immune system, its diagnostic and therapeutic aspect, the effect on immune escape, immune-checkpoint molecules, and the tumour microenvironment. We have also discussed the existing limitations, clinical success and the prospective use of miRNAs in cancer.

Magnetic nanoparticles in theranostics of malignant melanoma

Malignant melanoma is an aggressive tumor with a tendency to metastasize early and with an increasing incidence worldwide. Although in early stage, melanoma is well treatable by excision, the chances of cure and thus the survival rate decrease dramatically after metastatic spread. Conventional treatment options for advanced disease include surgical resection of metastases, chemotherapy, radiation, targeted therapy and immunotherapy. Today, targeted kinase inhibitors and immune checkpoint blockers have for the most part replaced less effective chemotherapies. Magnetic nanoparticles as novel agents for theranostic purposes have great potential in the treatment of metastatic melanoma. In the present review, we provide a brief overview of treatment options for malignant melanoma with different magnetic nanocarriers for theranostics. We also discuss current efforts of designing magnetic particles for combined, multimodal therapies (e.g., chemotherapy, immunotherapy) for malignant melanoma.

easier: interpretable predictions of antitumor immune response from bulk RNA-seq data

Immunotherapy with immune checkpoint blockers (ICB) is associated with striking clinical success, but only in a small fraction of patients. Thus, we need computational biomarker-based methods that can anticipate which patients will respond to treatment. Current established biomarkers are imperfect due to their incomplete view of the tumor and its microenvironment. We have recently presented a novel approach that integrates transcriptomics data with biological knowledge to study tumors at a more holistic level. Validated in four different solid cancers, our approach outperformed the state-of-the-art methods to predict response to ICB. Here, we introduce estimate systems immune response (easier), an R/Bioconductor package that applies our approach to quantify biomarkers and assess patients' likelihood to respond to immunotherapy, providing just the patients' baseline bulk-tumor RNA-sequencing (RNA-seq) data as input.

Bridging Radiotherapy to Immunotherapy: The IFN–JAK–STAT Axis

The unprecedented successes of immunotherapies (IOs) including immune checkpoint blockers (ICBs) and adoptive T-cell therapy (ACT) in patients with late-stage cancer provide proof-of-principle evidence that harnessing the immune system, in particular T cells, can be an effective approach to eradicate cancer. This instills strong interests in understanding the immunomodulatory effects of radiotherapy (RT), an area that was actually investigated more than a century ago but had been largely ignored for many decades. With the “newly” discovered immunogenic responses from RT, numerous endeavors have been undertaken to combine RT with IOs, in order to bolster anti-tumor immunity. However, the underlying mechanisms are not well defined, which is a subject of much investigation. We therefore conducted a systematic literature search on the molecular underpinnings of RT-induced immunomodulation and IOs, which identified the IFN–JAK–STAT pathway as a major regulator. Our further analysis of relevant studies revealed that the signaling strength and duration of this pathway in response to RT and IOs may determine eventual immunological outcomes. We propose that strategic targeting of this axis can boost the immunostimulatory effects of RT and radiosensitizing effects of IOs, thereby promoting the efficacy of combination therapy of RT and IOs.

Uveal Melanoma Metastasis

Uveal melanoma (UM) is characterized by relatively few, highly incident molecular alterations and their association with metastatic risk is deeply understood. Nevertheless, this knowledge has so far not led to innovative therapies for the successful treatment of UM metastases or for adjuvant therapy, leaving survival after diagnosis of metastatic UM almost unaltered in decades. The driver mutations of UM, mainly in the G-protein genes GNAQ and GNA11, activate the MAP-kinase pathway as well as the YAP/TAZ pathway. At present, there are no drugs that target the latter and this likely explains the failure of mitogen activated kinase kinase inhibitors. Immune checkpoint blockers, despite the game changing effect in cutaneous melanoma (CM), show only limited effects in UM probably because of the low mutational burden of 0.5 per megabase and the unavailability of antibodies targeting the main immune checkpoint active in UM. The highly pro-tumorigenic microenvironment of UM also contributes to therapy resistance. However, T-cell redirection by a soluble T-cell receptor that is fused to an anti-CD3 single-chain variable fragment, local, liver specific therapy, new immune checkpoint blockers, and YAP/TAZ specific drugs give new hope to repeating the success of innovative therapy obtained for CM.

Uveal Melanoma Metastasis

Uveal melanoma (UM) is characterized by relatively few, highly incident molecular alterations and their association with metastatic risk is deeply understood. Nevertheless, this knowledge has so far not led to innovate therapies for the successful treatment of UM metastases or for adjuvant therapy, leaving survival after diagnosis of metastatic UM almost unaltered in decades. The driver mutations of UM, mainly in the G-protein genes GNAQ and GNA11, activate the MAP-kinase pathway as well as the YAP/TAZ pathway. At present, there are no drugs that target the latter and this likely explains the failure of MEK-inhibitors. Immune checkpoint blockers, despite the game changing effect in cutaneous melanoma (CM) show only marginal effects in UM probably because of the low mutational burden of 0.5 per megabase and the unavailability of antibodies targeting the main immune checkpoint active in UM. The highly pro-tumorigenic microenvironment of UM also contributes to therapy resistance. However, T-cell redirection by a soluble T cell receptor that is fused to an anti-CD3 single-chain variable fragment, local, liver specific therapy, new immune checkpoint blockers and YAP/TAZ specific drugs give new hope to repeat the success of innovative therapy obtained for CM.

mRNA-Based Cancer Vaccines: A Therapeutic Strategy for the Treatment of Melanoma Patients

Malignant melanoma is one of the most aggressive forms of cancer and the leading cause of death from skin tumors. Given the increased incidence of melanoma diagnoses in recent years, it is essential to develop effective treatments to control this disease. In this regard, the use of cancer vaccines to enhance cell-mediated immunity is considered to be one of the most modern immunotherapy options for cancer treatment. The most recent cancer vaccine options are mRNA vaccines, with a focus on their usage as modern treatments. Advantages of mRNA cancer vaccines include their rapid production and low manufacturing costs. mRNA-based vaccines are also able to induce both humoral and cellular immune responses. In addition to the many advantages of mRNA vaccines for the treatment of cancer, their use is associated with a number of challenges. For this reason, before mRNA vaccines can be used for the treatment of cancer, comprehensive information about them is required and a large number of trials need to be conducted. Here, we reviewed the general features of mRNA vaccines, including their basis, stabilization, and delivery methods. We also covered clinical trials involving the use of mRNA vaccines in melanoma cancer and the challenges involved with this type of treatment. This review also emphasized the combination of treatment with mRNA vaccines with the use of immune-checkpoint blockers to enhance cell-mediated immunity.