Our first product candidate Vvax001, a therapeutic cancer vaccine against (pre)malignant cervical lesions, is currently in clinical development. We outsource process development and GMP manufacturing to experienced CMO’s, leading to a first clinical trial, which has been started in Q4-2016.
Cervical cancer is the third most common cancer among women worldwide. It is caused by infection with high-risk Human Papillomavirus (HPV). High-risk HPVs have the capacity to transform cervical epithelial cells by integrating the open reading frames encoding the viral early proteins E6 and E7 into the host cell genome. This integration may lead to constitutive overexpression of E6 and E7, mediating transformation of the cells to a malignant phenotype. Since the continued production of E6 and E7 is required for the maintenance of the transformed phenotype, E6 and E7 in fact represent tumor-specific antigens in cervical carcinoma and premalignant HPV-transformed cells. As a consequence, E6 and E7 are potential targets for immunotherapeutic intervention strategies involving induction or stimulation of cytotoxic T lymphocyte (CTL) activity against HPV-transformed cells.
We developed SFVeE6,7 as our lead product, based on an attenuated, recombinant Semliki Forest virus (rSFV), encoding HVP E6 and E7 and named it Vvax001. SFV represents an excellent platform for generating efficient vector systems for transient high-level gene expression for therapeutic cancer immunization. In wild type mice we demonstrated that Vvax001 induces robust HPV-specific cellular immune and memory responses, resulting in excellent therapeutic anti-tumor efficacy.
Based on our animal data, we conclude that the main advantage of Vvax001 is the full-blown activation of the immune system, characterized by or resulting in:
- a high CTL response
- a strong memory effect
- short antigen expression resulting in the activation of the correct effector and memory cells
- activation of danger signals, normally only activated by adjuvants
- a strong anti-tumor effect
- a partial breakage of the immunological tolerance / suppression
- no toxic reaction at the sites of injection
- a low dose
- ease of vaccination: two or three intramuscular vaccinations
In cervical cancer, patients have built up a certain degree of immunological tolerance. This puts high demands on potential immunotherapeutic strategies, since such approaches need to overcome this tolerance and suppression in order to be effective. Based our data gathered so far, Vvax001 has a potential to break this immunological tolerance / suppression due to the immune-boosting SFV delivery method. |
