Rational optimization of an innovative survivin therapeutic synthetic vaccine for treatment of cancers – OPTIVAX

Tumors often escape and even exploit the immune system to promote their survival, expansion and metastatization. However, tumor-specific T-cells retain the potential to effectively control and even eradicate large tumors, which led to the design of immunotherapeutic cancer vaccines. These have been shown to elicit specific tumor immunity with extended overall survival in a relatively small proportion of vaccinated patients. There is therefore a need to optimize therapeutic cancer vaccine design to increase their immunogenicity and clinical efficacy. This requires a rational selection of the tumor antigen target and of all vaccine components in order to boost both CD4+ and CD8+ T cell responses while limiting the regulatory T cell (Treg) induction and tumor escape mechanisms. Vaxeal has designed a novel generation of therapeutic cancer vaccine enabling to overcome limitations to current vaccine-based approaches. The proprietary vaccine (WO2007/036638) is composed of 3 long synthetic peptides (LSP) derived from survivin, an ubiquitous protein over-expressed and playing vital functions in large number of human tumors and metastatic tissues. LSPs are very attractive cancer vaccines as they are fully synthetic and as they are able to generate CD4+ and CD8+ T-cell responses, which showed promising clinical efficacy in patients with pre-neoplastic lesions.
The objective of this project is the rational development of an optimized LSP-based cancer therapeutic vaccine targeting the survivin tumor antigen to bring this vaccine as a first-generation product in human trial. The Work Program will investigate the effects of various factors, added or coupled to the LSPs, to boost their immunogenicity and anti-tumoral activity. The key factors to be tested include the LSPs chemical composition and synergy with immune adjuvants. Spontaneous immune responses against our proprietary LSPs will be also assessed in cancer patients to rationaly guide the selection of patients for the clinical trials. The optimized survivin vaccine will then enter in cGLP production scale-up and preliminary formal pharmaco-toxological development. All these data will constitute a relevant proof-of-concept to support the pre-clinical studies and to bring our vaccine to the doorstep of the clinic as a first-generation product. In parallel, the benefits of the synergistic combination with anti-angiogenic and chemotherapeutic compounds, known to alleviate immunosuppression, will be evaluated as a second-generation product for certain specific cancer indications. OPTIVAX consortium brings together diverse advanced expertise in tumor immunology and vaccine formulation, including T-cell response immuno-monitoring in clinical samples and pre-clinical animal models. It involves both clinicians and scientists from three research-intense accademic laboratories with a SME. Under the lead of exploitation manager VAXEAL, the consortium will exploit the results in their respective fields.