A new retrospective analysis of real-world data, published by cecava’s co-founder Saskia Biskup, MD PhD, shows that individualized neoepitope peptide-based treatments can induce strong and specific anti-tumor immune responses. Patients who developed immune responses against several tumor-specific neoepitopes showed prolonged survival. These findings are in line with cecava’s 2024 Nature Communications observational paper, where a significant survival benefit for neoepitope peptide-based treated patients with glioblastoma was reported.
Saskia Biskup, MD PhD, notes: “We have accompanied many of these patients closely over the past years. The consistent immune responses seen across both glioblastoma and IDH1-mutant glioma patients are remarkable. This highlights the potential of individualized neoepitope-directed immunotherapy and underlines the importance of further clinical evaluation.”
Overview of retrospective data on immunotherapy in gliomas
IDH1-mutated gliomas are among the most challenging brain tumors to treat. Standard therapies lack long-term control, and IDH inhibitors are currently approved only for low-grade disease. New therapeutic strategies are urgently needed, especially for aggressive late-stage forms.
In addition to standard-of-care, 52 patients with IDH1-mutant gliomas received individualized peptide-based treatments. Each treatment was individually developed based on the patient’s tumor mutation profile obtained by whole exome and transcriptome sequencing. From the identified tumor mutations, neoepitopes were derived and prioritized using a proprietary AI-based in silico pipeline. Among the neoepitopes selected (median 20 neoepitopes per patient) was at least one neoepitope targeting the tumor’s IDH1 mutation (most commonly R132H).
Neoepitope peptide-based treatments induce robust immune responses with good tolerability
The team demonstrated that the individualized neoepitope peptide-based treatments were generally well-tolerated and triggered strong immune responses in 98% of the patients. Importantly, both CD4⁺ and CD8⁺ T-cells were activated, which are central to recognizing and eliminating tumor cells. Most patients responded to multiple neoepitope peptides included in their treatment. In 89% of cases, the IDH1 mutation-derived peptide induced a measurable immune reaction.
Clinical relevance and broader implications
These results suggest that even tumors with a low to moderate tumor mutational burden, such as gliomas, can present actionable neoepitopes if selection is based on precise genomic profiling and AI-based neoepitope immunogenicity predictions. Notably, IDH-mutant glioma patients who mounted broader immune responses against numerous targeted neoepitopes showed prolonged survival.
Dirk Hadaschik, PhD, CSO of cecava, comments: “The results highlight that broadening the immune responses to multiple neoepitopes, also beyond IDH1, seems to be key to treating advanced brain cancers with immunotherapies effectively. Since the local distribution of mutations varies within such tumors, diversification of the immune response by neoepitope peptide-based treatments may support the effective immune attack against all tumor cells of a patient.”
Outlook
The retrospective analysis underscores the therapeutic potential of individualized peptide-based treatments in diffuse gliomas. It also supports the further development of both individualized and standardized immunotherapeutic strategies. Based on the encouraging observations from both retrospective analyses of real-world data, cecava is currently preparing a clinical trial to confirm the results under more standardized conditions. The ultimate goal is to obtain marketing authorization for the new treatment concept, ensuring that as many patients as possible can benefit from it.
For detailed insights, access the recent retrospective analysis here:
To learn more about the earlier findings in glioblastoma, see the 2024 Nature Communications article here:
About cecava
cecava GmbH is a biopharmaceutical immuno-oncology company located in Tuebingen (Germany). Founded in 2018, cecava’s mission is to develop individualized peptide cancer therapies (INPECT). The therapy is tailored to target the patient-individual tumor mutations. Through immunizations with the AI-selected neoepitope peptides, the immune system is activated and directed against the patient’s tumor. Based on encouraging real-world experience with this novel immunotherapy, clinical trials are currently being prepared. The company’s ultimate goal is to secure the approval for this innovative treatment, ensuring that as many cancer patients as possible may benefit.
