Gritstone Oncology Announces Data on Novel Shared Tumor-Specific Neoantigens Identified by its EDGE Platform and Contained Within its SLATE Immunotherapy
-Poster Presentation at
“Real tumor-specific neoantigens are rare, representing just one to two percent of all tumor mutations,” said
In order to identify shared TSNA, the neoantigen landscape across human cancer was comprehensively characterized using accurate prediction of HLA class I peptide presentation by EDGE. From over 24,000 patients with clinical cancer gene sequencing data, EDGE ranked a large number of candidate mutation/HLA pairs based on the probability of HLA-peptide presentation. EDGE predicted nearly 200 mutations to be possible shared neoantigens across indications. Through targeted HLA class I peptide mass spectrometry sequencing of human tumors and a novel in vitro system, Gritstone was able to demonstrate HLA presentation of more than 10 new HLA class I shared neoantigens, many of which were directly observed on real human tumors. This work is ongoing to evaluate the full set of TSNA predictions. Importantly, the immunogenicity of several of these shared neoantigens was confirmed by demonstrating the presence of cognate T-cell precursors in healthy donors. The poster can be accessed on the Investors & Media section of the
|Poster Presentation Details|
|Title:||Identification and Validation of Shared Neoantigens for Cancer Immunotherapy|
|Date:||Friday, November 8, 2019|
|Time:||7:00 a.m. – 8:00 p.m. ET|
|Location:||Poster Hall (Prince George AB)|
Ongoing Phase 1/2 Clinical Study
SLATE in combination with immune checkpoint blockade is being evaluated in a Phase 1/2 clinical study called GO-005 for the treatment of patients with advanced solid tumors, including metastatic non-small cell lung cancer, pancreatic ductal adenocarcinoma and microsatellite-stable colorectal cancer, as well as in patients with other solid tumor types who have relevant mutation/HLA (human leukocyte antigen) combinations. In the dose-escalation Phase 1, all patients receive a fixed dose of intramuscular adenovirus-based prime with three escalating doses (30, 100 and 300 µg) of intramuscular RNA-based boost vaccinations in combination with intravenous anti-PD-1 therapy. Following dose escalation of the RNA-based boost vaccine to 30 µg, subcutaneous anti-CTLA-4 is added to the treatment regimen.
SLATE is Gritstone’s shared neoantigen (“off-the-shelf”) immunotherapy. It is engineered to elicit a significant T-cell response (particularly CD8+ cytotoxic T cells) against encoded TSNA. SLATE immunotherapy consists of two components: first, a priming adenoviral vector, that has been shown to be highly immunogenic in humans in other disease settings, is used to deliver the cassette of 20 shared TSNA; and second, the same shared TSNA cassette is delivered using a self-amplifying RNA vector in a repeated boost sequence designed to drive and sustain high numbers of tumor-targeted T cells. These TSNA were identified by Gritstone using the EDGE artificial intelligence platform and tumor HLA peptide sequencing, and represent mutated gene sequences that are shared across patients (such as KRAS mutations). Suitable patients must possess both the appropriate DNA mutation and, importantly, a relevant HLA type that can present the mutant sequence to the patient’s T cells. Gritstone is continuing its research efforts to identify new TSNA which can enable the development of additional SLATE product candidates targeting different mutations and/or tumor types.
Gritstone Forward-Looking Statements
This press release contains forward-looking statements, including, but not limited to, statements related to the potential of Gritstone’s therapeutic programs. Such forward-looking statements involve substantial risks and uncertainties that could cause Gritstone’s research and clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the drug development process, including Gritstone’s programs’ early stage of development, the process of designing and conducting preclinical and clinical trials, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, Gritstone’s ability to successfully establish, protect and defend its intellectual property and other matters that could affect the sufficiency of existing cash to fund operations. Gritstone undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of the company in general, see Gritstone’s most recent Quarterly Report on Form 10-Q filed on
Wheelhouse Life Science Advisors
Source: Gritstone Oncology, Inc