Identification of Tumor Rejection Antigens for Breast Cancer Using a Mouse Tumor Rejection Model

2008 ◽  
Author(s):  
Mary L. Disis
Keyword(s):  
Breast Cancer ◽  
Tumor Rejection ◽  
Mouse Tumor ◽  
Rejection Antigens

Mouse tumor rejection antigens P815A and P815B : Two epitopes carried by a single peptide

1992 ◽  
Vol 22 (9) ◽  
pp. 2283-2288 ◽  
Author(s):  
Bernard Lethé ◽  
Beno??t Van den Eynde ◽  
Aline Van Pel ◽  
Giampietro Corradin ◽  
Thierry Boon
Keyword(s):  
Tumor Rejection ◽  
Mouse Tumor ◽  
Single Peptide ◽  
Rejection Antigens

995 Genes coding for tumor rejection antigens

1995 ◽  
Vol 31 ◽  
pp. S207-S208
Author(s):  
T. Boon ◽  
P. Van Der Bruggen ◽  
V. Brichard ◽  
A. Van Pel ◽  
P.G. Coulie ◽  
...  
Keyword(s):  
Tumor Rejection ◽  
Rejection Antigens

scholarly journals Targeting Chk1 in p53-deficient triple-negative breast cancer is therapeutically beneficial in human-in-mouse tumor models

2012 ◽  
Vol 122 (4) ◽  
pp. 1541-1552 ◽  
Author(s):  
Cynthia X. Ma ◽  
Shirong Cai ◽  
Shunqiang Li ◽  
Christine E. Ryan ◽  
Zhanfang Guo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Mouse Tumor ◽  
Tumor Models ◽  
Mouse Tumor Models

Chemotherapy-elicited exosomal miR-378a-3p and miR-378d to promote breast cancer stemness and chemoresistance via the activation of EZH2/STAT3 signaling.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12615-e12615
Author(s):  
Jin Zhang
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Neoadjuvant Chemotherapy ◽  
Pathologic Complete Response ◽  
Chemotherapeutic Agents ◽  
Cell Counting ◽  
Chemotherapy Response ◽  
Mouse Tumor ◽  
Response To Chemotherapy ◽  
Serum Exosomes

e12615 Background: Not all breast cancer (BC) patients who receive neoadjuvant chemotherapy achieve a pathologic complete response (pCR), but the reasons for this are unknown. Previous studies have shown that exosomes produced in the tumor microenvironment in response to chemotherapy promote a chemotherapy-resistant phenotype in tumors. However, the role of BC chemo-elicited exosomes in regulating chemoresistance is poorly understood. Methods: Using commercial kits, serum exosomes were extracted from patients before neoadjuvant chemotherapy, after one cycle of chemotherapy and after four cycles of chemotherapy consisting of doxorubicin (DOX) and paclitaxel (PTX). Their miRNAs were sequenced, and the correlation between the sequencing results and chemotherapy effects was further verified by RT-qPCR using patient serum exosomes. Cell Counting Kit-8 (CCK-8) was used to detect chemosensitivity. Stemness was assessed by CD44+/CD24- population analysis and mammosphere formation assays. Chromatin immunoprecipitation (ChIP) experiments were performed to verify the binding of signal transducer and activator of transcription 3 (STAT3) to the promoter of miRNAs. Results: Here, we provide clinical evidence that chemotherapy-elicited exosomal miR-378a-3p and miR-378d are closely related to the chemotherapy response and that exosomes produced by BC cells after stimulation with DOX or PTX deliver miR-378a-3p and miR-378d to neighboring cells to activate WNT and NOTCH stemness pathways and induce drug resistance by targeting Dickkopf 3 (DKK3) and NUMB. In addition, STAT3, which is enhanced by zeste homolog 2 (EZH2), bound to the promoter regions of miR-378a-3p and miR-378d, thereby increasing their expression in exosomes. More importantly, chemotherapeutic agents combined with the EZH2 inhibitor tazemetostat reversed chemotherapy-elicited exosome induced drug resistance in a nude mouse tumor xenograft model. Conclusions: This study revealed a novel mechanism of acquired chemoresistance whereby chemotherapy activates the EZH2/STAT3 axis in BC cells, which then secrete chemotherapy-elicited exosomes enriched in miR-378a-3p and miR-378d. These exosomes are absorbed by chemotherapy-surviving BC cells, leading to activation of WNT and NOTCH stem cell pathways via the targeting of DKK3 and NUMB and subsequently resulting in drug resistance. Therefore, blocking this adaptive mechanism during chemotherapy may reduce the development of chemotherapy resistance and maximize the therapeutic effect.

scholarly journals IMMU-24. A COMPREHENSIVE IN SILICO APPROACH TO DISCOVERING TUMOR REJECTION ANTIGENS IN MALIGNANT BRAIN TUMORS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi124-vi124
Author(s):  
Changlin Yang ◽  
Kyle Dyson ◽  
Oleg Yegorov ◽  
Duane Mitchell
Keyword(s):  
Brain Tumors ◽  
Mhc Class Ii ◽  
In Silico ◽  
Tumor Rejection ◽  
Reading Frame ◽  
Normal Tissues ◽  
Rnaseq Data ◽  
Actual Sequence ◽  
Or Genes ◽  
Rejection Antigens

Abstract BACKGROUND Proteins that can serve as effective tumor rejection antigens within brain tumors are poorly characterized. Current prediction algorithms relying on identification of mutated epitopes as neoantigens are limited in low mutational burden tumors. We have developed a multi-faceted computer algorighm for identifying tumor rejection antigens called the Open Reading Frame Antigen Network (ORAN). This pipeline provides a comprehensive solution for predicting brain tumor immunogenic targetable epitopes/transcripts. METHODS Human and murine RNASeq and WES data were QCed. Patients individual HLA-I and HLA-II haplotypes were predicted by highly customized Optitype and Phlat Algorithms. SNPs and Indels were called from tumors WES and read through matched RNASeq data. 19,131 transcripts expression were counted per TOIL algorithm. Tumor associate antigens(TAA) of individual patient or murine tumors were selected by setting a cutoff of Transcripts Per Million (TPM) > 1 on individual patient’s tumor, while RNA Seq data from 7000 normal tissues was used to identify tumor unique transcripts. Actual sequence of HLA and SNPed Consenses TAA(CTAA) were called. Only expressed mutations and personalized TAAs were used for antigenic epitope predictions. All neoepitopes were screened against a human reference proteomic library to guarantee that epitopes were not shared by other expressed isoforms or genes. In silico validation were preformed to cross validate predictions made by ORAN. RESULTS In medullobastoma (N=121 samples), ORAN gives an average of 15.6 MHC class I restricted neoepitopes,11.9 epitopes encoded by Indels and with 33.2 MHC class II restricted neoepitopes and 16.2 Indel antigens per patient. The TAAs of each patient reaches average 256 antigenic epitopes per patient. ORAN also predicts the exact HLA and neo-antigens from a validated neoantigens vaccine dataset (Gros A Nat Med 2016). CONCLUSION ORAN accurately identifies validated neoantigens and provides a comprehensive list of potential tumor rejection antigens within human and murine brain tumors.

scholarly journals Functionalized nanoparticles with targeted antibody to enhance imaging of breast cancer in vivo

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Jesse S. Chen ◽  
Jingwen Chen ◽  
Somnath Bhattacharjee ◽  
Zhengyi Cao ◽  
Han Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Detection ◽  
Tumor Imaging ◽  
Growth Factor Receptor ◽  
Therapeutic Monitoring ◽  
Mouse Tumor ◽  
Her 2 ◽  
Epidermal Growth ◽  
Magnetic Resonance Imaging Mri

Abstract Background Targeted contrast nanoparticles for breast tumor imaging facilitates early detection and improves treatment efficacy of breast cancer. This manuscript reports the development of an epidermal growth factor receptor-2 (HER-2) specific, bi-modal, dendrimer conjugate to enhance computed tomography (CT) and magnetic resonance imaging (MRI) of HER-2-positive breast cancer. This material employs generation 5 poly(amidoamine) dendrimers, encapsulated gold nanoparticles, chelated gadolinium, and anti-human HER-2 antibody to produce the nanoparticle contrast agent. Results Testing in two mouse tumor models confirms this contrast agent’s ability to image HER-2 positive tumors. Intravenous injection of this nanoparticle in mice bearing HER-2 positive mammary tumors significantly enhances MRI signal intensity by ~ 20% and improves CT resolution and contrast by two-fold. Results by flow cytometry and confocal microscopy validate the specific targeting of the conjugate and its internalization in human HER-2 positive cells. Conclusion These results demonstrate that this nanoparticle conjugate can efficiently target and image HER-2 positive tumors in vivo and provide a basis for the development of this diagnostic tool for early detection, metastatic assessment and therapeutic monitoring of HER-2 positive cancers.

scholarly journals Monocyte-derived APCs are central to the response of PD1 checkpoint blockade and provide a therapeutic target for combination therapy

2020 ◽  
Vol 8 (2) ◽  
pp. e000588 ◽  
Author(s):  
Sjoerd T T Schetters ◽  
Ernesto Rodriguez ◽  
Laura J W Kruijssen ◽  
Matheus H W Crommentuijn ◽  
Louis Boon ◽  
...  
Keyword(s):  
T Cell ◽  
Combination Therapy ◽  
Tumor Therapy ◽  
Immune Checkpoint Blockade ◽  
Tumor Rejection ◽  
Checkpoint Blockade ◽  
Response To Treatment ◽  
Mouse Tumor ◽  
Sequencing Data ◽  
Tumor Models

BackgroundPD1 immune checkpoint blockade (αPD1 ICB) has shown unparalleled success in treating many types of cancer. However, response to treatment does not always lead to tumor rejection. While αPD1 ICB relies on cytotoxic CD8+ T cells, antigen-presenting cells (APCs) at the tumor site are also needed for costimulation of tumor-infiltrating lymphocytes (TILs). It is still unclear how these APCs develop and function before and during αPD1 ICB or how they are associated with tumor rejection.MethodsHere, we used B16 mouse melanoma and MC38 colorectal carcinoma tumor models, which show differential responses to αPD1 ICB. The immune composition of ICB insensitive B16 and sensitive MC38 were extensively investigated using multi-parameter flow cytometry and unsupervised clustering and trajectory analyses. We additionally analyzed existing single cell RNA sequencing data of the myeloid compartment of patients with melanoma undergoing αPD1 ICB. Lastly, we investigated the effect of CD40 agonistic antibody on the tumor-infiltrating monocyte-derived cells during αPD1 ICB.ResultsWe show that monocyte-derived dendritic cells (moDCs) express high levels of costimulatory molecules and are correlated with effector TILs in the tumor microenvironment (TME) after αPD1 ICB only in responding mouse tumor models. Tumor-resident moDCs showed distinct differentiation from monocytes in both mouse and human tumors. We further confirmed significant enrichment of tumor-resident differentiated moDCs in patients with melanoma responding to αPD1 ICB therapy compared with non-responding patients. Moreover, moDCs could be targeted by agonistic anti-CD40 antibody, supporting moDC differentiation, effector T-cell expansion and anti-tumor immunity.ConclusionThe combined analysis of myeloid and lymphoid populations in the TME during successful and non-successful PD1 ICB led to the discovery of monocyte-to-DC differentiation linked to expanding T-cell populations. This differentiation was found in patients during ICB, which was significantly higher during successful ICB. The finding of tumor-infiltrating monocytes and differentiating moDCs as druggable target for rational combination therapy opens new avenues of anti-tumor therapy design.

Human esophageal carcinomas frequently express the tumor-rejection antigens ofMAGE genes

1995 ◽  
Vol 63 (4) ◽  
pp. 523-526 ◽  
Author(s):  
Hiroshi Inoue ◽  
Masaki Mori ◽  
Jian Li ◽  
Koshi Mimori ◽  
Masayuki Honda ◽  
...  
Keyword(s):  
Tumor Rejection ◽  
Esophageal Carcinomas ◽  
Rejection Antigens
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