On April 15, 2024 Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company working to develop the world’s most potent vaccines, reported that a paper detailing the development of its "off-the-shelf" neoantigen platform, SLATE, recently published in Nature Medicine (Press release, Gritstone Bio, APR 15, 2024, View Source [SID1234642068]). The paper, "A shared neoantigen vaccine combined with immune checkpoint blockade for advanced metastatic solid tumors: phase 1 trial interim results," describes a novel immunodominance hierarchy of tumor neoantigens (including KRAS) that Gritstone discovered in Phase 1 translational studies and leveraged to develop SLATE-KRAS, a "pure" KRAS-directed candidate that demonstrated superior immunogenicity to the initial version in a subsequent Phase 2 study and is currently being evaluated in a novel cell therapy-vaccine combination study run by Steven A. Rosenberg of the National Cancer Institute (NCT06253520).
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"The publication of these findings in Nature Medicine highlights the promise of our ‘off-the-shelf’ or shared neoantigen approach in solid tumors, one of the many elements embedded within our mission to develop the world’s most potent vaccines," said Andrew Allen, M.D., Ph.D., Co-founder, President, and Chief Executive Officer of Gritstone bio. "Our team’s innovative work to develop, optimize and validate SLATE positions Gritstone with two promising platforms to execute against our neoantigen-directed approach to oncology. It also enabled the pioneering collaboration that we are currently advancing with Dr. Rosenberg of the NCI, a luminary in the field. SLATE is ready for ‘plug and play’ application across a spectrum of solid tumors and could serve as a great complementary platform to GRANITE, our personalized vaccine program. We continue to have great conviction that both approaches could unlock new levels of immune responses for patients with solid tumors."
"This important publication underscores that a deep understanding of the mechanism and performance of therapeutic neoantigens in humans is likely critical for success in the promising field of neoantigen-directed immunotherapy. It also demonstrates our ability to select tumor antigens and optimize cassette design to elicit a potent antigen-specific immune response," said Karin Jooss, Ph.D., Executive Vice President, and Head of R&D at Gritstone bio. "We believe we have a leading understanding of the hierarchy of antigen presentation and competition – a great example outlined in this paper, where we took SLATE from bench to bedside to bench, and back – and have applied that understanding to optimize the design of our oncology vaccines. The learnings and techniques described add to Gritstone’s already robust body of clinical insights to drive potent tumor-specific T cell responses to neoantigens, a unique potential advantage in the field."
Results from the SLATE 1/2 Study
The data published in Nature Medicine report the interim safety, tolerability and immunogenicity results from the Phase 1 portion of the Phase 1/2 clinical trial (NCT03953235) assessing the off-the-shelf vaccine SLATEv1 in patients with advanced/metastatic solid tumors. SLATEv1 utilizes a heterologous ChAd68 followed by samRNA-based vaccine regimen encoding 20 shared neoantigens targeting multiple recurrent mutations in several oncogenes, including KRAS, TP53, BRAF and CTNNB1. Neoantigens were identified using Gritstone bio’s proprietary neoantigen prediction platform, EDGETM, and selected based on shared mutation and matched HLA frequencies in patient populations with solid tumors. Biased T cell responses toward HLA-matched TP53 neoantigens encoded in the vaccine relative to KRAS neoantigens expressed by the patients’ tumors, indicated a previously unknown hierarchy of neoantigen immunodominance that may impact the therapeutic efficacy of multi-epitope shared neoantigen vaccines. These data led to the development of SLATE-KRAS, a vaccine focused on KRAS-derived neoantigens that subsequently was evaluated in the Phase 2 portion of the clinical study. Initial Phase 2 data suggesting an increased vaccine induced T cell response were presented in September 2022 (press release).
To view all of Gritstone bio’s scientific publications, visit gritstonebio.com/publications.
About SLATE ("off-the-shelf" neoantigen vaccine program)
Gritstone’s neoantigen-based vaccine programs, GRANITE (personalized) and SLATE ("off-the-shelf) are engineered to elicit a significant T cell response for patients with solid tumors. Like GRANITE, SLATE uses Gritstone’s proprietary epitope identification platform (EDGE) and vaccine vectors (Chimpanzee Adenovirus and self-amplifying mRNA) to deliver each patient a set of neoantigens that are predicted to drive a T cell response. Unlike GRANITE, SLATE delivers a set of neoantigens that are shared across a subset of cancer patients based on common gene mutations, such as KRAS mutations. In Phase 1/2 study, SLATE-KRAS demonstrated positive results in patients with late-line non-small cell lung cancer and microsatellite stable colorectal cancer. With these results, Gritstone believes the SLATE platform is ready for ‘plug and play’ application across solid tumor indications and shared tumor neoantigen classes.