Bavarian Nordic’s cancer immunotherapy candidates, PROSTVAC and CV-301 both employ the VF-TRICOM technology, which includes a vaccinia-based priming dose (V) followed by multiple fowlpox-based boosting doses (F), and incorporates 3 human immune costimulatory molecules (TRICOM: TRIad of COstimulatory Molecules) engineered to enhance immune system response to the tumor target. Both the priming and boosting doses encode one or more tumor-associated antigens, intended to activate the body’s immune system against these antigens.
The data from clinical studies conducted to date suggest that this heterologous prime/boost regimen leads to an anticancer immune response of greater magnitude and quality than regimens using only a homologous repeating treatment approach.
How it works
|Poxvirus-based “prime/boost” platform robustly stimulates the innate and adaptive immune systems||Tumor-associated antigens (TAAs) are expressed on antigen-presenting cells (APCs) and stimulate a specific, progressively expanding immune response||TRICOM (TRIad of COstimulatory Molecules) includes the genes for 3 natural human costimulatory molecules intended to facilitate T cell/APC interaction and strengthen the anticancer immune response|
- Targeted tumor-associated antigens
Both the prime and boost doses express a well-established tumor antigen, enabling them to provoke specific immune responses to principally target only those cells with that target protein, known also as the tumor-associated antigen (TAA). Bavarian Nordic’s poxvirus-based immunotherapy is designed to alert the immune system to the danger posed by cancer cells with that TAA
- TRICOM (TRIad of COstimulatory Molecules)
Each recombinant immunotherapy candidate contains genes for the 3 natural human immune-enhancing costimulatory molecules, LFA-3, ICAM-1, and B7.1, collectively designated TRICOM. Recombinant immunotherapies co-expressing these 3 costimulatory molecules have been shown to have synergistic effects on anticancer responses in mice compared with immunotherapies expressing costimulatory molecules individually
Prime/boost vaccination strategy
Data from preclinical and clinical studies suggest that the immune response can be optimized by using a poxvirus-based “prime/boost” immunotherapeutic regimen. As a result, our poxvirus-based active immunotherapy regimens include a vaccinia-based priming dose followed by multiple fowlpox-based boosting doses. This strategy has shown an enhanced immune response compared with either agent alone.
Gulley JL, Madan RA, Tsang KT, et al. Immune impact induced by PROSTVAC (PSA-TRICOM), a therapeutic vaccine for prostate cancer. Cancer Immunol Res. 2014;2:133-141.
Mandl SJ, Rountree RB, Dalpozzo K, et al. Immunotherapy with MVA-BN®-HER2 induces HER-2-specific Th1 immunity and alters the intratumoral balance of effector and regulatory T cells. Cancer Immunol Immunother. 2012;61:19-29.