Gritstone - Model EDGE - Proprietary Technologies
From Scientific Platform
The first pillar of our immunotherapy is our understanding of antigens and neoantigens, and specifically which ones will be transcribed, translated, processed and presented on a cell surface by Human leukocyte antigen (HLA) molecules; and therefore will be visible to T cells. We accomplish this through the use of Gritstone EDGETM, our proprietary machine learning-based platform.
-
Most popular related searches
Details
Developing cancer immunotherapies that include tumor-specific neoantigens presents a challenge due to their nature – tumors typically have hundreds of mutations, but only a small percentage of those mutations result in true tumor-specific neoantigens that are. To address this challenge, we trained EDGE’s novel integrated neural network model architecture with millions of datapoints from hundreds of tumor and normal tissue samples from patients of various ancestries. This enables us to use sequence data from a patient’s routine biopsy to predict which mutations will generate tumor-specific neoantigens most likely to be presented on the tumor cell surface by the HLA. EDGE has shown a significant improvement in accuracy for predicting tumor presented peptides in comparison with publicly available approaches. We believe that mutations selected by our EDGE platform have a much higher likelihood of being useful targets for immunization than mutations selected using previous methods.
Vaccines against viruses ideally generate both neutralizing antibody responses to whole proteins on the virus surface, but also T cell responses to the short fragments of viral proteins which are displayed on the surface of virus-infected cells (once inside a cell, a virus is invisible to antibodies which operate outside the cell). All viral proteins are foreign to the human immune system, but only short fragments of proteins (called peptides) are displayed on the cell surface by HLA and visible to T cells. The specific fragments presented will vary between subjects depending upon the HLA type of the subject (conceptually similar to someone’s blood type but more complex). Identification of key viral protein fragments that can drive strong T cell responses is an output of Gritstone’s EDGE platform.
The second pillar is our ability to develop and manufacture potent immunotherapies utilizing (neo)antigens to drive the patient’s immune system to attack and destroy diseased cells. Gritstone’s vaccine platform uses a two-part heterologous prime-boost system to accomplish this robust immune response. Grounded in infectious disease vaccine immunology, this two-step immunization utilizes a viral prime and a self-amplifying mRNA (samRNA) boost. Our immunotherapies are designed to educate the patient’s T cells to recognize and attack diseased cells displaying the encoded antigens.
With the development and commercialization of immunotherapy drugs such as checkpoint inhibitors, the field of immuno-oncology is transforming the treatment of patients with cancer. However, cures remain elusive, and many cancer patients experience only modest clinical benefit.
A challenge facing the field of immuno-oncology is to develop new approaches to drive potent, tumor-specific immune responses that provide therapeutic benefit to a large number of patients.
Gritstone’s scientific founders published an important discovery in immuno-oncology: in patients with solid tumors who respond to checkpoint inhibitors, mutations in the tumor’s DNA produce critical new targets. These targets, called tumor-specific neoantigens, are unique to tumor cells and can be recognized and targeted for destruction by the patient’s own immune system.
Neoantigens represent a new class of targets for advancing cancer immunotherapy and have been validated in cancer patients as critical T-cell targets. However, the identification of neoantigens presents a key therapeutic challenge. Some tumors have hundreds of mutations, but only a minority result in true tumor-specific neoantigens found on the surface of tumor cells – making them difficult to find and target appropriately.
Neoantigens can be classified as either patient-specific, meaning each patient has their own unique neoantigens, or shared, in which common driver mutations are found across some patients.
Customer reviews
No reviews were found for Gritstone - Model EDGE - Proprietary Technologies. Be the first to review!