Browse
Submit Data
Databases
API
Help

Dataset Information

10 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CD81 is a novel immunotherapeutic target for B cell lymphoma.

ABSTRACT: The tetraspanin CD81 was initially discovered by screening mAbs elicited against a human B cell lymphoma for their direct antiproliferative effects. We now show that 5A6, one of the mAbs that target CD81, has therapeutic potential. This antibody inhibits the growth of B cell lymphoma in a xenograft model as effectively as rituximab, which is a standard treatment for B cell lymphoma. Importantly, unlike rituximab, which depletes normal as well as malignant B cells, 5A6 selectively kills human lymphoma cells from fresh biopsy specimens while sparing the normal lymphoid cells in the tumor microenvironment. The 5A6 antibody showed a good safety profile when administered to a mouse transgenic for human CD81. Taken together, these data provide the rationale for the development of the 5A6 mAb and its humanized derivatives as a novel treatment against B cell lymphoma.

SUBMITTER: Vences-Catalan F

PROVIDER: S-EPMC6605745 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

CD81 is a novel immunotherapeutic target for B cell lymphoma.

Vences-Catalán Felipe F Kuo Chiung-Chi CC Rajapaksa Ranjani R Duault Caroline C Andor Noemi N Czerwinski Debra K DK Levy Ronald R Levy Shoshana S

The Journal of experimental medicine 20190523 7

The tetraspanin <i>CD81</i> was initially discovered by screening mAbs elicited against a human B cell lymphoma for their direct antiproliferative effects. We now show that 5A6, one of the mAbs that target <i>CD81</i>, has therapeutic potential. This antibody inhibits the growth of B cell lymphoma in a xenograft model as effectively as rituximab, which is a standard treatment for B cell lymphoma. Importantly, unlike rituximab, which depletes normal as well as malignant B cells, 5A6 selectively k ...[more]

PMID: 31123084

Similar Datasets

TREX1 as a Novel Immunotherapeutic Target.

Project description:Mutations in the TREX1 3' → 5' exonuclease are associated with a spectrum of autoimmune disease phenotypes in humans and mice. Failure to degrade DNA activates the cGAS-STING DNA-sensing pathway signaling a type-I interferon (IFN) response that ultimately drives immune system activation. TREX1 and the cGAS-STING DNA-sensing pathway have also been implicated in the tumor microenvironment, where TREX1 is proposed to degrade tumor-derived DNA that would otherwise activate cGAS-STING. If tumor-derived DNA were not degraded, the cGAS-STING pathway would be activated to promote IFN-dependent antitumor immunity. Thus, we hypothesize TREX1 exonuclease inhibition as a novel immunotherapeutic strategy. We present data demonstrating antitumor immunity in the TREX1 D18N mouse model and discuss theory surrounding the best strategy for TREX1 inhibition. Potential complications of TREX1 inhibition as a therapeutic strategy are also discussed.

| S-EPMC8047136 | biostudies-literature

Upcoming immunotherapeutic combinations for B-cell lymphoma.

Project description:After initial introduction for B-cell lymphomas as adjuvant therapies to established cancer treatments, immune checkpoint inhibitors and other immunotherapies are now integrated in mainstream regimens, both in adult and pediatric patients. We here provide an overview of the current status of combination therapies for B-cell lymphoma, by in-depth analysis of combination therapy trials registered between 2015-2020. Our analysis provides new insight into the rapid evolution in lymphoma treatment, as propelled by new additions to the treatment arsenal. We conclude with prospects on upcoming clinical trials which will likely use systematic testing approaches of more combinations of established chemotherapy regimens with new agents, as well as new combinations of immunotherapy and targeted therapy. Future trials will be set up as basket or umbrella-type trials to facilitate the evaluation of new drugs targeting specific genetic changes in the tumor or associated immune microenvironment. As such, lymphoma patients will benefit by receiving more tailored treatment that is based on synergistic effects of chemotherapy combined with new agents targeting specific aspects of tumor biology and the immune system.

| S-EPMC9326875 | biostudies-literature

ZNF165 as a potential novel immunotherapeutic target for gastric cancer

Project description:Background: Cancer testis antigens (CTAs) are an extensive gene family with a unique expression pattern restricted to testis tissues, but aberrantly high expressed in a variety of cancer tissues. In view of this, CTAs are typically considered as efficient biomarkers and targets of immunotherapy. However, limited information is available regarding CTAs as immunotherapeutic targets for gastric cancer (GC) patients. Herein, we evaluated the expression levels of CTAs in both Eastern and Western GC patients and elucidate the expression pattern and functions of a novel CTAs.

2022-08-09 | GSE210662 | GEO

Unlocking the potential of CD70 as a novel immunotherapeutic target for non-small cell lung cancer.

Project description:Although normally restricted to activated T and B cells and mature dendritic cells, constitutive expression of CD70, a member of the tumor necrosis family, has been described in both hematological and solid tumors, where it increases tumor cell and regulatory T cell survival by signaling through its receptor, CD27.We have assessed the co-expression of CD70 and CD27 in non-small cell lung cancer (NSCLC) by immunohistochemistry to explore a correlation between expression of the protein and tumor histologic subtype, genetic aberrations and prognosis. Furthermore, we tested the ability of ARGX-110, a CD70-blocking antibody, to induce NK cell-mediated cytotoxicity.Our results revealed CD70 expression on the surface of both primary and metastatic NSCLC tumor cells and in the tumor microenvironment. Moreover, CD27-expressing tumor infiltrating lymphocytes were found adjacent to the tumor cells, suggesting active CD70-mediated signaling. Finally, we have shown that ARGX-110, has potent cytotoxic effects on CD70+ NSCLC cell lines.

| S-EPMC4537027 | biostudies-literature

Novel target and treatment agents for natural killer/T-cell lymphoma.

Project description:The rapidly increasing use of high-throughput screening had produced a plethora of expanding knowledge on the molecular basis of natural killer/T-cell lymphoma (NKTCL), which in turn has revolutionized the treatment. Specifically, the use of asparaginase-containing regimens has led to substantial improvement in survival outcomes in NKTCL patients. Novel treatment strategies that are currently under development include cell-surface-targeted antibodies, immune checkpoint inhibitors, Epstein-Barr virus targeted cytotoxic T lymphocyte, immunomodulatory agents, chimeric antigen receptor T cells, signaling pathway inhibitors and epigenetic targeted agents. In almost all cases, initial clinical studies of newly developed treatment are conducted in patients relapsed, and refractory NKTCL due to very limited treatment options. This review summarizes the results of these novel treatments for NKTCL and discusses their potential for likely use in NKTCL in a wider setting in the future.

| S-EPMC10362755 | biostudies-literature

Mesothelin as a novel biomarker and immunotherapeutic target in human glioblastoma.

Project description:Glioblastoma multiforme (GBM) presents the most malignant form of glioma, with a 5-year survival rate below 3% despite standard therapy. Novel immune-based therapies in improving treatment outcomes in GBM are therefore warranted. Several molecularly defined targets have been identified mediating anti-GBM cellular immune responses. Mesothelin is a tumor-associated antigen (TAA) which is expressed in several solid tumors with different histology. Here, we report the immunological significance of mesothelin in human malignant glioma. Expression of mature, surface-bound mesothelin protein was found to bein human GBM defined by immunofluorescence microscopy, and on freshly isolated, single cell suspension of GBM tumor cells and GBM tumor cell lines, determined by based on flow cytometric analysis. Peripheral blood (PB) from patients with GBM, stimulated with mesothelin peptides and IL-2, IL-15 and IL-21, exhibited increased antigen-specific IFN-γ and TNF-α production. Anti-mesothelin directed T-cell responses could also be detected in tumor - infiltrating lymphocytes (TIL) isolated from GBM speciments. Furthermore, T cells cultured in the presence of IL-2, IL-15 and IL-21 displayed enhanced mesothelin-specific CD4+ and CD8+ subset proliferation, based on ELISA and flow cytometric readouts. Mesothelin-specific IgG antibodies as well as (shed) mature mesothelin protein were detected in plasma samples from patients with GBM by indirect ELISA. Finally yet importantly, we identified distinct immune recognition hotspots within the mature mesothelin component, defined by peptide-specific IFN-γ responses from peripheral T-cells from patients with GBM. Mesothelin may therefore qualify as a viable target for immunotherapeutic approaches for patients with GBM.

| S-EPMC5655191 | biostudies-literature

Maternal embryonic leucine zipper kinase is a novel target for diffuse large B cell lymphoma and mantle cell lymphoma.

Project description:Diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) are among the most aggressive B cell non-Hodgkin lymphomas. Maternal embryonic leucine zipper kinase (MELK) plays a role in cancer cell cycle progression and is associated with poor prognosis in several cancer cell types. In this study, the role of MELK in DLBCL and MCL and the therapeutic potential of MELK targeting is evaluated. MELK is highly expressed in DLBCL and MCL patient samples, correlating with a worse clinical outcome in DLBCL. Targeting MELK, using the small molecule OTSSP167, impaired cell growth and survival and induced caspase-mediated apoptosis in the lymphoma cells. Western blot analysis revealed that MELK targeting decreased the phosphorylation of FOXM1 and the protein levels of EZH2 and several mitotic regulators, such as Cdc25B, cyclin B1, Plk-1, and Aurora kinases. In addition, OTSSP167 also sensitized the lymphoma cells to the clinically relevant Bcl-2 inhibitor venetoclax by strongly reducing Mcl1 levels. Finally, OTSSP167 treatment of A20-inoculated mice resulted in a significant prolonged survival. In conclusion, targeting MELK with OTSSP167 induced strong anti-lymphoma activity both in vitro and in vivo. These findings suggest that MELK could be a potential new target in these aggressive B cell malignancies.

| S-EPMC6861269 | biostudies-literature

DLK1: a novel target for immunotherapeutic remodeling of the tumor blood vasculature.

Project description:Tumor blood vessels are frequently inefficient in their design and function, leading to high interstitial fluid pressure, hypoxia, and acidosis in the tumor microenvironment (TME), rendering tumors refractory to the delivery of chemotherapeutic agents and immune effector cells. Here we identified the NOTCH antagonist delta-like 1 homologue (DLK1) as a vascular pericyte-associated antigen expressed in renal cell carcinomas (RCC), but not in normal kidney tissues in mice and humans. Vaccination of mice bearing established RCC against DLK1 led to immune-mediated elimination of DLK1(+) pericytes and to blood vessel normalization (i.e., decreased vascular permeability and intratumoral hypoxia) in the TME, in association with tumor growth suppression. After therapeutic vaccination, tumors displayed increased prevalence of activated VCAM1(+)CD31(+) vascular endothelial cells (VECs) and CXCL10, a type-1 T cell recruiting chemokine, in concert with increased levels of type-1 CD8(+) tumor-infiltrating lymphocytes (TIL). Vaccination against DLK1 also yielded (i) dramatic reductions in Jarid1B(+), CD133(+), and CD44(+) (hypoxia-responsive) stromal cell populations, (ii) enhanced tumor cell apoptosis, and (iii) increased NOTCH signaling in the TME. Coadministration of a ?-secretase inhibitor (N-[N-(3,5-Difluorophenacetyl-l-alanyl)]-(S)-phenylglycine t-butyl ester (DAPT)) that interferes with canonical NOTCH signaling resulted in the partial loss of therapeutic benefits associated with lentivirus encoding full-length murine (lvDLK1)-based vaccination.

| S-EPMC3808139 | biostudies-literature

Ovarian granulosa cell tumor characterization identifies FOXL2 as an immunotherapeutic target.

Project description:Granulosa cell tumors (GCT) are rare ovarian malignancies. Due to the lack of effective treatment in late relapse, there is a clear unmet need for novel therapies. Forkhead Box L2 (FOXL2) is a protein mainly expressed in granulosa cells (GC) and therefore is a rational therapeutic target. Since we identified tumor infiltrating lymphocytes (TILs) as the main immune population within GCT, TILs from 11 GCT patients were expanded, and their phenotypes were interrogated to determine that T cells acquired late antigen-experienced phenotypes and lower levels of PD1 expression. Importantly, TILs maintained their functionality after ex vivo expansion as they vigorously reacted against autologous tumors (100% of patients) and against FOXL2 peptides (57.1% of patients). To validate the relevance of FOXL2 as a target for immune therapy, we developed a plasmid DNA vaccine (FoxL2-tetanus toxin; FoxL2-TT) by fusing Foxl2 cDNA with the immune-enhancing domain of TT. Mice immunization with FoxL2-TT controlled growth of FOXL2-expressing ovarian (BR5) and breast (4T1) cancers in a T cell-mediated manner. Combination of anti-PD-L1 with FoxL2-TT vaccination further reduced tumor progression and improved mouse survival without affecting the female reproductive system and pregnancy. Together, our results suggest that FOXL2 immune targeting can produce substantial long-term clinical benefits. Our study can serve as a foundation for trials testing immunotherapeutic approaches in patients with ovarian GCT.

| S-EPMC7455139 | biostudies-literature

Novel Immunotherapeutic Approaches to Target Alpha-Synuclein and Related Neuroinflammation in Parkinson's Disease.

Project description:The etiology of Parkinson's disease (PD) is significantly influenced by disease-causing changes in the protein alpha-Synuclein (aSyn). It can trigger and promote intracellular stress and thereby impair the function of dopaminergic neurons. However, these damage mechanisms do not only extend to neuronal cells, but also affect most glial cell populations, such as astroglia and microglia, but also T lymphocytes, which can no longer maintain the homeostatic CNS milieu because they produce neuroinflammatory responses to aSyn pathology. Through precise neuropathological examination, molecular characterization of biomaterials, and the use of PET technology, it has been clearly demonstrated that neuroinflammation is involved in human PD. In this review, we provide an in-depth overview of the pathomechanisms that aSyn elicits in models of disease and focus on the affected glial cell and lymphocyte populations and their interaction with pathogenic aSyn species. The interplay between aSyn and glial cells is analyzed both in the basic research setting and in the context of human neuropathology. Ultimately, a strong rationale builds up to therapeutically reduce the burden of pathological aSyn in the CNS. The current antibody-based approaches to lower the amount of aSyn and thereby alleviate neuroinflammatory responses is finally discussed as novel therapeutic strategies for PD.

| S-EPMC6406239 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data