CAR-Based Immunotherapy of Solid Tumours—A Survey of the Emerging Targets

Maher, John; Davies, Daniel

doi:10.3390/cancers15041171

Cited by 14 publications

(7 citation statements)

References 180 publications

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“…Irofulven, for instance, is a semisynthetic medication made from illudin S, a toxin discovered in the Omphalotus illudens . Irofulven has been tested in phases I and II clinical studies, showing promise in its ability to treat malignancies of the breast, blood, colon, sarcoma, prostate, lungs, ovary, and pancreas, as well as the brain and central nervous system [ 171 , 172 ]. Another anticancer substance discovered in fungi Akanthomyces muscarius and Nigrospora sphaerica is called aphidicolin.…”

Section: Resultsmentioning

confidence: 99%

Wild Mushrooms: A Hidden Treasure of Novel Bioactive Compounds

Gebreyohannes,

Sbhatu

2023

International Journal of Analytical Chemistry

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Secondary metabolites are hidden gems in mushrooms. Understanding these secondary metabolites’ biological and pharmacological effects can be aided by identifying them. The purpose of this work was to profile the mycochemical components of the extracts of Auricularia auricula judae, Microporus xanthopus, Termitomyces umkowaani, Trametes elegans, and Trametes versicolor to comprehend their biological and pharmacological capabilities. Mushroom samples were collected from Kenya’s Arabuko–Sokoke and Kakamega National Reserved Forests and identified using morphological and molecular techniques. Chloroform, 70% ethanol, and hot water solvents were used to extract the mycochemical components. Gas chromatography mass spectrometry (GC-MS) was used to analyze the chloroform, 70% ethanol, and hot water extracts of all the species examined. A total of 51 compounds were isolated from all extracts and classified as carboxylic acids, esters, phenols, fatty acids, alcohol, epoxides, aldehydes, fatty aldehydes, isoprenoid lipids, and steroids. Tetracosamethyl-cyclododecasiloxane (18.90%), oleic acid (72.90%), phenol, 2, 6-bis (1, 1-dimethylethyl)-4-methyl-, and methylcarbamate (26.56%) were all found in high concentrations in A. auricular judae, M. xanthopus, T. umkowaani, T. elegans, and T. versicolor, respectively. Fatty acids make up the majority of the compounds isolated from the T. elegans chloroform extract and the T. umkowaani 70% ethanol extract, respectively. Particularly, these fatty acids play crucial roles in the anti-inflammatory, hypocholesterolemic, anticancer, and antibiofilm formation activities. These bioactive elements indicate that the extracts of five wild mushrooms may be reliable sources of secondary metabolites for therapeutic development. Therefore, additional research is required to comprehend the usefulness of these chemicals in many functional areas and to improve the present understanding of macrofungi.

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Section: Resultsmentioning

confidence: 99%

Wild Mushrooms: A Hidden Treasure of Novel Bioactive Compounds

Gebreyohannes,

Sbhatu

2023

International Journal of Analytical Chemistry

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“…Upregulation of EPHA3 in the tumor-initiating cell population of gliomas and in tumor cells maintained in an undifferentiated state contributed to their tumorigenic potential; this was evident from the reduction in tumorigenic potential upon EPHA3 attenuation (30). A phase I clinical trial evaluating the anti-EPHA3 monoclonal antibody, ifabotuzumab, in patients with recurrent glioblastoma has demonstrated its e cacy in targeting the tumor microenvironment, whilst sparing normal tissues (31,32). Elevated expression of EPHA3 has been associated with aggressive tumor characteristics and an unfavorable prognosis in HCC; in addition, downregulation of EPHA3 mitigates HCC cell invasiveness via modulation of VEGF signaling pathways (33); nonetheless, therapeutic intervention targeting EPHA3 have not been attempted.…”

Section: Discussionmentioning

confidence: 99%

VIM-AS1, regulated by CpG methylation, cooperates with IGF2BP1 to inhibit tumor aggressiveness via EPHA3 degradation in hepatocellular carcinoma

Han,

Ko,

Jung

et al. 2024

Preprint

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Background Early tumor recurrence observed in hepatocellular carcinoma (HCC) remains challenging, as the mechanisms involved have not been completely elucidated. Microvascular invasion is associated with early recurrence; however, well-established biomarkers for diagnosis and predicting prognosis are lacking. In this study, we aimed to identify DNA methylation sites predicting liver cancer patient prognosis and validate HCC aggressiveness molecular mechanisms. Methods DNA methylome data from HCC patient samples (CGRC and TCGA) were analyzed to identify hypermethylated CpG sites. RNA-sequencing was performed on HCC cells with modulated expression of VIM-AS1, a long non-coding RNA regulated by CpG methylation. In vitro and in vivo studies investigated the intracellular molecular mechanism of action of VIM-AS1, and the CRISPR-dCas9 system was used for validating the potential of targeted DNA methylation as a therapeutic target. Results We observed that cg02746869, significantly associated with HCC patient prognosis, acted as a pivotal regulatory site for VIM-AS1. Suppression of VIM-AS1 due to methylation profoundly influenced the HCC cellular dynamics, specifically impairing the motility and invasiveness of cancer cells. This effect involved modulating EPHA3 expression and its subsequent interaction with the m6A-associated protein, IGF2BP1. Additionally, we observed that modifications in the methylation state of cg02746869 directly affected the invasive properties of HCC cells, underscoring the critical role of this methylation site in the oncogenic behavior of HCC. Conclusions Our results highlighted the significant role of DNA methylation in controlling lncRNA expression and its impact on HCC pathophysiology. Thus, cg02746869 is an emergent biomarker for prognostic evaluation and therapeutic intervention in HCC.

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“…To further explore the role of KLK2 in PRAD, we analyzed KLK2 gene expression using the TCGA (The Cancer Genome Atlas) repository through a resource termed UALCAN. We explored the presence of KLK2 in relation to patient ethnic origin, given the different genomic background described between racial groups [11,12]. As can be seen in Supplementary Figure S1A, no significant differences were observed between the Caucasian and African American populations, although the number of patients in this last group was very small.…”

Section: Expression Of Klk2 In Cancermentioning

confidence: 99%

Genomic and Immunologic Correlates in Prostate Cancer with High Expression of KLK2

Paniagua-Herranz,

Moreno,

Nieto-Jiménez

et al. 2024

IJMS

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The identification of surfaceome proteins is a main goal in cancer research to design antibody-based therapeutic strategies. T cell engagers based on KLK2, a kallikrein specifically expressed in prostate cancer (PRAD), are currently in early clinical development. Using genomic information from different sources, we evaluated the immune microenvironment and genomic profile of prostate tumors with high expression of KLK2. KLK2 was specifically expressed in PRAD but it was not significant associated with Gleason score. Additionally, KLK2 expression did not associate with the presence of any immune cell population and T cell activating markers. A mild correlation between the high expression of KLK2 and the deletion of TMPRSS2 was identified. KLK2 expression associated with high levels of surface proteins linked with a detrimental response to immune checkpoint inhibitors (ICIs) including CHRNA2, FAM174B, OR51E2, TSPAN1, PTPRN2, and the non-surface protein TRPM4. However, no association of these genes with an outcome in PRAD was observed. Finally, the expression of these genes in PRAD did not associate with an outcome in PRAD and any immune populations. We describe the immunologic microenvironment on PRAD tumors with a high expression of KLK2, including a gene signature linked with an inert immune microenvironment, that predicts the response to ICIs in other tumor types. Strategies targeting KLK2 with T cell engagers or antibody–drug conjugates will define whether T cell mobilization or antigen release and stimulation of immune cell death are sufficient effects to induce clinical activity.

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CAR-Based Immunotherapy of Solid Tumours—A Survey of the Emerging Targets

Cited by 14 publications

References 180 publications

Wild Mushrooms: A Hidden Treasure of Novel Bioactive Compounds

Wild Mushrooms: A Hidden Treasure of Novel Bioactive Compounds

VIM-AS1, regulated by CpG methylation, cooperates with IGF2BP1 to inhibit tumor aggressiveness via EPHA3 degradation in hepatocellular carcinoma

Genomic and Immunologic Correlates in Prostate Cancer with High Expression of KLK2

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