Angelina M. Cicerchia
A5067224206- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Biosimilars and Bioanalytical Methods
- Calcium signaling and nucleotide metabolism
- Immune Cell Function and Interaction
- Cancer-related molecular mechanisms research
- Protein Degradation and Inhibitors
- Adenosine and Purinergic Signaling
- RNA modifications and cancer
- Immunotherapy and Immune Responses
- Viral Infectious Diseases and Gene Expression in Insects
- Virus-based gene therapy research
- Peptidase Inhibition and Analysis
- RNA Research and Splicing
- Nanoplatforms for cancer theranostics
- Cytomegalovirus and herpesvirus research
- Synthesis and Biological Evaluation
- interferon and immune responses
- Viral-associated cancers and disorders
- Immune cells in cancer
Harvard University
2023-2025
Massachusetts General Hospital
2023-2025
Center for Cancer Research
2024-2025
Broad Institute
2024
University of Massachusetts Amherst
2021-2022
Significance N6-methyladenosine (m 6 A) modifications play important roles in regulating RNA fate, particular during viral infection. However, it remains unclear whether m A can also act any antiviral capacity. During Kaposi’s sarcoma–associated herpesvirus infection, while most messenger are degraded by the nuclease SOX, a subset of transcripts stringently escape degradation. Our study reveals that one such transcript, interleukin-6, acquires an modification course which allows to recruit...
Novel therapeutic strategies are needed to improve the efficacy of chimeric antigen receptor (CAR) T cells as a treatment solid tumors. Multiple tumor microenvironmental factors thought contribute resistance CAR T-cell therapy in tumors, and appropriate model systems identify examine these using clinically relevant biospecimens limited. In this study, we examined activity B7-H3-directed (B7-H3.CAR-T) 3D microfluidic cultures patient-derived organotypic spheroids (PDOTS) then confirmed...
<p>Supplemental Figure S7 | Supporting data that targeting TBK1 prevents CAR-T cell dysfunction.</p>
<p>Supplemental Figure S5 | Supporting data that targeting TBK1 prevents CAR-T cell dysfunction.</p>
<p>Supplemental Figure S6 | Supporting data that targeting TBK1 prevents CAR-T cell dysfunction.</p>
<p>PDOTS patient data (accompanying Fig. 1)</p>
<p>Supplemental Figure S8 | Supporting data that targeting TBK1 prevents CAR-T cell dysfunction.</p>
<div>Abstract<p>Novel therapeutic strategies are needed to improve the efficacy of chimeric antigen receptor (CAR) T cells as a treatment solid tumors. Multiple tumor microenvironmental factors thought contribute resistance CAR T-cell therapy in tumors, and appropriate model systems identify examine these using clinically relevant biospecimens limited. In this study, we examined activity B7-H3–directed (B7-H3.CAR-T) 3D microfluidic cultures patient-derived organotypic spheroids...
<p>Supplemental Figure S9 | Supporting data for single cell RNA sequencing of CAR-T in 3D co-cultures with PDOTS.</p>
<p>PDOTS patient data (accompanying Fig. 3)</p>
<p>Supplemental Figure S4 | Supporting data for ex vivo profiling of PD-1 blockade and TBK1 inhibition in combination with B7-H3.CAR-T cells using PDOTS.</p>
<p>Supplementary Figure S2 | Supporting data for the In vitro characterization and efficacy of B7-H3.CAR-T cells.</p>
<p>Supplemental Figure S3 | Supporting data for <i>ex vivo</i> profiling of B7-H3.CAR-T cells using PDOTS.</p>
<p>PDOTS patient data (accompanying Fig. 2)</p>
<p>Supplemental Figure S11 | Supporting data that targeting TBK1 sensitizes cancer cells to CAR-T cell-derived TNFα/IFNγ.</p>
<p>Supplementary Figure S1 | Supporting data demonstrating B7-H3 expression in melanoma and other cancers.</p>
<p>Supplemental Figure S10 | Supporting data for single cell RNA sequencing of native tumor-infiltrating lymphocytes following CAR-T challenge in 3D co-cultures with PDOTS.</p>
Abstract T cell exhaustion is a major driver of immune checkpoint blockade (ICB) resistance and clinically effective strategies to prevent or reverse restore ICB sensitivity are lacking. CD38, an ecto-enzyme involved in NAD+ catabolism, highly expressed exhausted CD8+ cells human melanoma, yet its role remains be elucidated. Here we show that CD38+CD8+ enriched during tumor progression following unsuccessful treatment strongly associated with melanoma. Chronic TCR activation type I...
A central problem in cancer immunotherapy with immune checkpoint blockade (ICB) is the development of resistance, which affects 50% patients metastatic melanoma 1,2 . T cell exhaustion, resulting from chronic antigen exposure tumour microenvironment, a major driver ICB resistance 3 Here, we show that CD38, an ecto-enzyme involved nicotinamide adenine dinucleotide (NAD + ) catabolism, highly expressed exhausted CD8 cells and associated resistance. Tumour-derived CD38 hi are dysfunctional,...
<h3>Background</h3> Terminally exhausted CD8+ T cells, resulting from chronic antigen exposure in the tumor microenvironment, are defined by loss of effector function, decreased proliferative potential, and associated with limited response to immune checkpoint blockade (ICB).<sup>1</sup> CD38 is an ecto-enzyme, involved NAD+ catabolism.<sup>2</sup> that was shown be expressed terminally cells melanoma correlate lack ICB,<sup>3</sup> although its specific role cell exhaustion therapeutic...
Abstract Cancer immunotherapy with immune checkpoint blockade (ICB) has transformed the treatment of melanoma, although intrinsic or acquired resistance develops in nearly half patients. Tumor-infiltrating CD8+ T lymphocytes (TILs) are key determinants anti-tumor immunity melanoma and other cancers, single-cell RNA-sequencing identified cell states associated improved clinical response to ICB, as well adoptive therapy (ACT). Despite these advances, strategies identify analyze tumor-reactive...
Abstract Despite the unprecedented success of immune checkpoint blockade (ICB) in melanoma and other cancers, therapeutic resistance remains a major challenge. CD38, an ecto-enzyme involved NAD+ catabolism, is upregulated dysfunctional/exhausted CD8+ T cells human melanoma. As enrichment dysfunctional associated with lack response to ICB, depletion via enhanced CD38 activity has been diminished response, we hypothesized that might represent attractive target overcome ICB. While shown augment...
<h3>Background</h3> The majority of patients treated with immunotherapy do not have durable treatment responses. Therefore, there is an urgent need to identify early non-invasive biomarkers for response. <h3>Methods</h3> In this study, we performed plasma proteomic analysis >700 proteins at three timepoints on 174 metastatic melanoma immune checkpoint blockade (ICB). We then expanded our analyses >3000 a larger cohort 250 deeper exploration baseline and on-treatment predictive response...