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Santa Cruz, CA, United States

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Contemplated cancer treatments comprise recursive analysis of patient-, cancer-, and location-specific neoepitopes from various biopsy sites of a patient after treatment or between successive rounds of immunotherapy and/or chemotherapy to inform further immunotherapy. Recursive analysis preferably includes various neoepitope attributes to so identify treatment relevant neoepitopes.


Patent
NantOmics LLC | Date: 2016-10-12

Methods and compositions for preparation and use of recombinant viruses or other recombinant expression systems are presented in which neoepitopes are first identified in a patient- and cancer-specific manner and then further filtered by HLA-match to the patient. Selected neoepitopes are then expression using sequence elements that direct the expressed neoepitope to the HLA-type (MHC-I and/or MHC-II subtype) that has desirable affinity to the filtered neoepitope.


Systems and methods are presented that allow for predicting treatment response of a tumor to a checkpoint inhibitor. In one exemplary aspect, the treatment response is directly associated with a relatively high number of patient- and tumor-specific immunologically visible neoepitopes. Specific mutational patterns in the nucleic acid encoding the neoepitope may be further indicative of treatment response.


Patent
NantOmics LLC | Date: 2016-10-12

Contemplated antiviral/cancer treatments comprise analysis of neoepitopes from viral DNA that has integrated into the host genome, and design of immunotherapeutic agents against such neoepitopes.


Patent
Nantomics LLC and Nant Holdings IP LLC | Date: 2015-09-03

Various devices, systems, structures and methods are disclosed related to securely authorizing a transaction by synchronizing digital genomic data with associated synthetic genomic variants. An embodiment of the present invention utilizes digital genomic data associated with an entity, such as a person, who may utilize a genome-based security device to complete a transaction. In one embodiment, a person may use a genome-based security device to communicate with an external device over a wireless or other communication interface, synchronize digital genomic data and an associated synthetic variant received from the external device with digital genomic data and associated synthetic variant stored on the genome-based security device.


PubMed | NantOmics LLC, Urbino University, Amgen, University of Chicago and Azienda Ospedali Riuniti Marche Nord
Type: | Journal: Cancer | Year: 2016

MET gene amplification and Met protein overexpression may be associated with a poor prognosis. The MET/Met status is typically determined with fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), respectively. Targeted proteomics uses mass spectrometry-based selected reaction monitoring (SRM) to accurately quantitate Met expression. FISH, IHC, and SRM analyses were compared to characterize the prognostic value of MET/Met in gastroesophageal adenocarcinoma (GEC).Samples from 447 GEC patients were analyzed for MET gene amplification (FISH) and Met protein expression (IHC and SRM). Cox proportional hazards models and Kaplan-Meier estimates were applied to explore relations between Met, overall survival (OS), and clinical/pathological characteristics. Spearmans rank coefficient was used to assess the correlation between parameters.Patients with MET-amplified tumors had worse OS when: the MET/centromere enumeration probe for chromosome 7 FISH ratio was2 (hazard ratio [HR], 3.13; 95% confidence interval [CI], 1.84-5.33), the MET gene copy number was 5 (HR, 2.51; 95% CI, 1.45-4.34), or10% of the cells had 15 copies (HR, 4.28; 95% CI, 2.18-8.39). Similar observations were made with Met protein overexpression by IHC (1+intensity in25% of the tumor cell membrane: HR, 1.39; 95% CI, 1.04-1.86) or SRM (400 amol/g: HR, 1.76; 95% CI, 1.06-2.90). A significant correlation was observed between MET FISH/Met IHC, MET FISH/Met SRM, and Met IHC/Met SRM; only MET FISH and Met SRM were independent negative prognostic biomarkers in multivariate analyses.MET amplification and overexpression, assessed by multiple methods, were associated with a worse prognosis in univariate analyses. However, only MET amplification by FISH and Met expression by SRM were independent prognostic biomarkers. Compared with IHC, SRM may provide an added benefit for informed decisions about Met-targeted therapy. Cancer 2016. 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.


PubMed | NantOmics LLC, University of California at Santa Cruz, Active Motif, Inc. and Buck Institute for Research on Aging
Type: Journal Article | Journal: Breast cancer research and treatment | Year: 2015

FOXM1 is a key transcription factor regulating cell cycle progression, DNA damage response, and a host of other hallmark cancer features, but the role of the FOXM1 cistrome in driving estrogen receptor-positive (ER+) versus estrogen receptor-negative (ER-) breast cancer clinical outcomes remains undefined. Chromatin immunoprecipitation sequencing (ChIP-Seq) coupled with RNA sequencing (RNA-Seq) analyses was used to identify FOXM1 target genes in breast cancer cells (MCF-7) where FOXM1 expression was either induced by cell proliferation or repressed by p53 upregulation. The prognostic performance of these FOXM1 target genes was assessed relative to FOXM transcript levels and a 61-gene proliferation score (PS) for their ability to dichotomize a pooled cohort of 683 adjuvant chemotherapy-nave, node-negative breast cancer cases (447 ER+, 236 ER-). Differences in distant metastasis-free survival (DMFS) between the dichotomized expression groups were determined by Cox proportional hazard modeling. Proliferation-associated FOXM1 upregulation induced a set of 145 differentially bound and expressed genes (direct targets), and these demonstrated minimal overlap with differentially bound and expressed genes following FOXM1 repression by p53 upregulation. This proliferation-associated FOXM1 cistrome was not only better at significantly predicting metastatic outcome of ER+ breast cancers (HR: 2.8 (2.0-3.8), p=8.13E-10), but was the only parameter trending toward significance in predicting ER- metastatic outcome (HR: 1.6 (0.9-2.9), p=0.087). Our findings demonstrate that FOXM1 target genes are highly dependent on the cellular context in which FOXM1 expression is modulated, and a newly identified proliferation-associated FOXM1 cistromic signature best predicts breast cancer metastatic outcome.


Specific mutations of FGFR3 (S249C) and of TP53 (V272M) are identified as being characteristic of breast cancer, and of having utility in diagnosis and prognosis of an individual with breast cancer. Systems and methods useful for identification of such mutations are also presented.


Patent
Nantomics LLC | Date: 2015-09-04

Systems and methods for genomic analysis are contemplated in which idiosyncratic markers or marker constellations are employed to characterize and compare genomic sequences. In especially preferred aspects, the idiosyncratic markers are predetermined SNPs and a marker profile is used in a sample record to so allow cross reference to other marker profiles of other sequences.


Contemplated panomic systems and methods significantly improve accuracy of genetic testing by taking into account matched normal data and expression levels of various genes in diseased tissue. Analysis and physician guidance is further improved by combining so identified clinically relevant changes with pathway analysis to thereby allow for classification of a tumor and/or identification of potentially druggable targets within affected pathways.

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