Other PTMS

2022--Direct Identification and Quantification of Neoantigens from Minute Amount of Clinical Biopsy Sample --- published on Cancers

In recent years, neoantigens are becoming popular cancer therapeutic targets under intensive studies by almost all major oncology pharmaceuticals. However, who are the target patients? Does the patient with a "correct" mutation and a "correct" HLA allele indeed present the "correct" neoantigen? Is this individual's neoantigen copy number high enough for immunotherapy? AI predictions based on NGS genomic information have been proven incapable of answering these questions. Immunopeptidome through mass spectrometry is dominated by disease-irrelevant peptide sequences.  There is no existing way to identify and quantify neoantigens from a minute amount of clinical biopsy sample, such as 50 mg tissue or less. Valid-NEO is developed to fit this demanding clinical need through combining our proprietary multi-omics platforms including NGS-based ultra-rare mutation calling technique, DEEPER-SeqS, and our unique clinical proteomics platform, Complete360^®, with additional hardware innovations (Ref. 1).

1. Publication: Valid-NEO: A Multi-Omics Platform for Neoantigen Detection and Quantification from Limited Clinical Samples.

2022--Identify and Quantify Neoantigens derived from Human endogenous retroviruses (HERVs) --- published on Science Advances

Human endogenous retroviruses (HERVs) represent 8% of the human genome. Working with, ErVaccine Technologies, our scientists identified neoantigens encoded by HERVs across a broad spectrum of cancers, and this finding may help enable next-generation therapeutic vaccines and cellular immunotherapies targeting these so-called “unconventional” tumor antigens (Ref 1). These antigens are shared by different tumor types. They would prove useful as personalized cancer therapeutic targets for a large number of patients. Along the side when we are keep on improving and developing our own disease detection and companion diagnostic pipelines, we are excited to be working with a large number of collaborators to implement our multi-omics platforms in their different clinical and basic research projects.

1. Publication: Identification of shared tumor epitopes from endogenous retroviruses inducing high avidity cytotoxic T cells for cancer immunotherapy.

2021--Therapeutic Neoantigens Encoded by Oncogene K-Ras --- published on Science Immunology

K-Ras is one of the most highly mutated oncogenes in cancers. The neoantigens encoded by K-Ras can be presented by many different types of cancer cells. Here we utilized our multi-omics neoantigen validation pipeline to detect and quantify K-Ras neoantigens from a variety of cancer samples (Ref 1.). We found that the K-Ras as well as several other oncogenes can be presented on cancer cell surface, but at extremely low copy numbers.  We adopted a variety of internal control system to measure their abundance down to <1 copy per cell level. To come up with an actionable strategy, the therapeutic team at JHU developed bispecific antibodies that can target the neoantigens we identified, and deliver dramatic therapeutic effects to mice. These findings are significant in the way that it opens a gate to developing pan-cancer immunotherapeutic agents that can treat a large number of patients sharing cancer hotspot mutations. Identifying such neoantigens is the first step in this campaign and is being accomplished by Complete Omics Inc.

1. Publication: Bispecific antibodies targeting mutant RAS neoantigens.

2021--Direct Quantification of Neoantigens Like Never Before --- published on Science

Genetic changes in human genome are the driving force for all cancers. Different patients have different sets of mutation profiles even for the  patients who all have the same disease. For decades, doctors, cancer researchers, and pharmaceutical companies have been working tirelessly trying to find a way to treat each person's unique disease in a highly personalized way that will reach the maximum treatment efficacy with the lowest side effects. Complete Omics, working with leaders in cancer therapeutics, has developed pipelines based on our multi-omics techniques through which we clearly observe and quantify personalized therapeutic targets encoded by the most frequently mutated tumor suppressor gene TP53. We validated and quantified the TP53 neoantigens on the surfaces of cancers and provided information to healthcare providers to support their decision on if or not to adopt a highly personalized cancer treatment targeting these neoantigens and when to use it (Ref 1). These findings provided the 1st-hand evidence for cancer therapeutics without the uncertainty that comes with predictions.

1. Publication: Targeting a neoantigen derived from a common TP53 mutation.

2019--First Pipeline for Direct Detection and Quantification of Neoantigens --- published on Cancer Immunology Research

Cancer-linked genetic mutations can code for mutant proteins, which can then be processed by proteasomes into peptides that are presented by human leukocyte antigen (HLA) molecules, triggering the body's immune response. The idea that such mutant peptides can trigger an immune response is fundamental to immunotherapies like checkpoint inhibitors as well as cancer vaccines that present the body with these peptides to generate an immune reaction. However, while the rise of next-generation sequencing has allowed researchers to identify a large number of cancer-linked mutations, actually detecting these mutation-associated neo-antigens, or MANAs, at the peptide level remains difficult. The fact that a mutant is present at the genetic level does not mean it will be produced at the protein level, and, even if it is, that is no guarantee that it will be processed and presented by HLA molecules. This has proved a challenge for, for instance, personalized cancer vaccine development. Our technology (Ref. 1) provide the 1st pipeline for detecting personalized cancer therapeutic targets. Our method has been reported by public media and has a significant impact in cancer research (Ref. 2).

1. Publication: Direct Detection and Quantification of Neoantigens.
2. Selected Media: Hopkins Team Develops Mass Spec Method to Detect Cancer Neoantigens | Genomeweb