Our Technology
For our pioneering approach, we combine cutting-edge technologies with our proprietary AI-based in silico pipeline in order to identify and prioritize the clinically most relevant immunogenic neoepitopes for treatment. Through our innovative platform technology, we guarantee a high degree of standardization, leading to the timely manufacture of individually tailored products consistently meeting the highest quality standards. Guided by actual patient experiences that deepen our understanding of cecava’s immunotherapy, we are continuously refining our processes to further improve patient outcomes. Our commitment to progress is evidenced through regular publications in high-profile, peer-reviewed journals.
Mode of Action
The basis of cecava’s technology is that each tumor acquires novel mutations during its development, leading to alterations in the sequence of proteins. Parts of such proteins (peptides) are presented on the tumor cell surface. If these presented peptides carry tumor mutation-derived alterations (neoepitopes), they may be sensed as foreign by immune cells (T cells). Upon recognition, these T cells can kill such tumor cells. Importantly, neoepitopes derived from tumor mutations are only presented by tumor cells and not by other healthy tissues. Thus, neoepitopes are not only highly tumor-specific but also new to the immune system, making them highly immunogenic and, therefore, ideal targets for cancer immunotherapies. cecava aims to exploit this weak spot of cancers by developing personalized peptide vaccines that are tailored to the patient-individual tumor mutations and neoepitopes. For vaccine manufacturing, the identification and selection of the clinically most relevant set of neoepitope peptides are guided by cecava’s proprietary artificial intelligence-based algorithms. Repeated vaccination with neoepitope peptides elicits a profound immune response against the tumor, which may lead to its destruction.
For immunization the patient-individual set of tumor mutation-derived neoepitope peptides is injected into the skin of the patient. There the peptides are taken up by so-called antigen-presenting cells (APC) which process the neoepitope peptides and present them on their surface via the HLA complex. Short neoepitopes are presented by APC via HLA class I molecules and may be recognized by cytotoxic T cells (also called CD8+ T cells). The subset of CD8+ T cells which recognizes a specific HLA-presented neoepitope becomes activated and expands. After migrating into the tumor, these activated cytotoxic T cells are able to recognize and kill tumor cells presenting the matching mutation-derived neoepitope via HLA class I molecules on their surface. In addition, APC may present longer neoepitope peptides via HLA class II molecules, which can be recognized by T helper cells (also called CD4+ T cells). Upon neoepitope recognition, this population of immune cells becomes activated and through release of factors promotes the activation and expansion of CD8+ T cells. Inside the tumor, such activated CD4+ T cells can additionally orchestrate the anti-tumor response of many distinct immune cells. Therefore, cecava’s approach aims for the activation of both neoepitope-specific CD8+ and CD4+ T cells to induce the most profound anti-tumor immune response.
Our Platform Technology
Although cecava tailors each vaccine to the highly patient-individual tumor mutations and neoepitopes, the manufacturing workflow always follows standardized rules and procedures, guaranteeing a highly active and reproducibly potent product meeting the highest quality standards.
First, a tumor and a matched normal sample of a cancer patient are sequenced to identify the tumor-specific mutations. From these, peptide sequences are derived, which comprise the respective tumor mutation-specific alterations. Next, a proprietary in silico pipeline is applied to predict which of these potential neoepitope peptide candidates may be presented by the tumor and recognized by the immune system (patent pending). From the prioritized list, the clinically most relevant neoepitopes are selected. These peptides are produced synthetically and manufactured into an injectable vaccine solution.
Importantly, this standardized approach is universally applicable to all solid and hematological cancers. One focus of cecava’s active research is the further development of superior artificial intelligence-based algorithms for the identification and prioritization of potent immunogenic neoepitopes with high clinical utility.
Real-World Experience
Using the approach described above, cecava’s co-founder Saskia Biskup has successfully treated around 500 cancer patients suffering from tumors of very diverse origins. Patients were vaccinated in her private doctor’s office in Germany in the setting of individual treatment attempts. The neoepitope vaccines were well tolerated, with mainly mild and transient side effects. The majority of patients developed robust, often long-lasting immune responses to the vaccine. Additionally, the comparison with historical data indicates that vaccination improves the survival of patients with various types of cancer. Based on this real-world experience, cecava further improves the algorithms to predict the most immunogenic neoepitopes and selects the most promising treatment strategies and disease indications for clinical development.