19P - Preclinical and clinical significance of VEGF deprivation in ovarian cancer through a specific active immunotherapy

Background

Vascular endothelial Growth factor (VEGF) has an important role in the physiology of normal ovaries and is a major player in the pathogenesis of OvCan. We have designed HEBERSaVax which is an active immunotherapy approach based on the use of a functionally deficient VEGF 121 isoform as antigen combined with an adjuvant. On immunocompetent mice, the ID8 model resembles the advanced stages of human OvCan and intervention results offer data potentially translatable to the clinical setting. Two sequential phase I clinical trials with single HEBERSaVax treatment have been concluded in patients with advanced solid tumors including subjects with advanced OvCan. A phase II clinical trial in this oncologic setting was recently finished. Herein we present data on HEBERSaVax effects on tumor development and reshaping of the microenvironment in OvCan.

Methods

C57BL/6 mouse tumor ID8 model was used to evaluate the vaccine effects in cancer growth control and tumor microenvironment remodeling. Immune response and cytokines concentrations were assessed by ELISA. Ascitic leukocytes were characterized by flow cytometry. Serum and leukocyte samples from selected OvCan patients (n=9) from the phase I clinical trials (RPCEC00000102 and RPCEC00000155) were also analyzed. Human anti-VEGF antibodies and cytokines were determined by ELISA. The cellular response was evaluated by IFN-γ ELISPOT.

Results

HEBERSaVax-based treatment increases the survival of ID8 tumor-bearing mice by reducing the ascites loads. An increase in VEGF-specific antibodies were detected in mice ascitic fluids, in parallel to a reduction of VEGF levels. The numbers of T lymphocytes and the expression of MHCII in macrophages were increased in the ascitic fluid. Data analyses from OvCan patients in clinical trials revealed that decreased or stabilized VEGF serum levels, positive anti-VEGF titers, and cellular responses, were related to an increase in survival. Processing of phase II clinical trial (RPCEC00000246) immune variables evaluations is ongoing (n=38, final data: ESMO).

Conclusions

Our findings indicate that HEBERSavax’s impact on preclinical ID8 settings might be translatable to a positive outcome in advanced OvCan patients.

Clinical trial identification

RPCEC00000102, RPCEC00000155 and RPCEC00000246.

Editorial acknowledgement

Legal entity responsible for the study

Center for Genetic Engineering and Biotechnology.

Funding

HEBERBiotec.

Disclosure

All authors have declared no conflicts of interest.