Scientific Excellence Required in Two Essential Elements
The successful development of tumor-specific neoantigen-targeted immunotherapies for cancer patients requires scientific excellence across two essential elements:
- The ability to predict which of a tumor’s many DNA mutations create neoantigens
- The ability to deliver these neoantigens to patients in a highly immunogenic context to drive a strong tumor-specific immune response
Leveraging both the latest insights into the nature of anti-tumor immune responses and our proprietary technology platform, Gritstone effectively addresses both elements. We identify neoantigens within the broad landscape of gene mutations with a unique deep learning prediction model trained on a large database of human tumors presenting peptides on the tumor cell surface. We place these neoantigens into a highly immunogenic neoantigen delivery vehicle and administer them to a patient to generate tumor-specific T-cell responses against the neoantigen to destroy the tumor.
Gritstone is working hard to ensure that our personalized immunotherapy will be available broadly within the community setting where most cancer patients receive treatment. For each patient, our therapeutic starts with a routine clinical biopsy and is delivered with a simple intramuscular injection.
Gritstone’s process for developing a personalized neoantigen immunotherapy for a cancer patient involves the following steps:
Routine Biopsy: A routine clinical biopsy is taken from a patient, and a sample is sent to Gritstone.
Tumor-Specific Neoantigen Prediction: We apply next-generation sequencing (NGS) and a deep learning model based on human tumors to characterize the tumor at a molecular level and select neoantigens for generating a tumor- and patient-specific immunotherapy.
Personalized Neoantigen Immunotherapy: We then send the selected neoantigens to our manufacturing facility, where they are synthesized to build a personalized neoantigen cassette that is part of the patient-specific immunotherapy. To ensure quality of the immunotherapy and control timelines and costs, we are building our own manufacturing facility to produce personalized neoantigen immunotherapies on an industrial scale.
We have learned from the infectious disease community that the strategy of using two different delivery components has increased efficacy in human treatments. To activate a potent immune response against the neoantigens within the cassette, we are deploying a heterologous prime/boost immunization approach based on viral vector systems.
Simple Injection: After the viral and RNA-based vectors are generated, they are formulated and packaged in vials and sent to the patient’s physician, where they can be administered to the patient with a simple intramuscular injection in the community setting, where most people with cancer are treated.
The personalized neoantigen immunotherapy is administered in combination with immune checkpoint inhibitors to improve immune responses, tumor response rates, and patient survival.