SANTAVAC

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SANTAVAC

SANTAVAC is a universal antigenic composition developed by proteomics and cell culture technologies intended for the preparation of cancer vaccines against different types of solid tumors.. The development of SANTAVAC started in 2005 under the guidance of Dr. Lokhov and further supported by BioBohemia LLC. Contributions to SANTAVAC development at different times were made by Bruker (in proteomic technology) and the Institute of Biomedical Chemistry (Moscow). The SANTAVAC mechanism of action is based on the heterogeneity of the cells lining the vessels (endothelial cells) and consists of polypeptides which are similar to tumor-vessel surface antigens. SANTAVAC vaccination elicits an immune response that targets tumor vessels. Using proteomic technology, referred to as the 'cell proteomic footprint' that allows direct profiling of cell surface antigens, the developers of SANTAVAC detailed the surface antigen profiles to describe their behavior when endothelial cells are exposed to different tumor cells. Thus, a way of modifying endothelial cell phenotypes was developed that was markedly different from the phenotype expressed by vascular cells in healthy tissues closely resembling the phenotype observed on cells lining vessels in solid tumors. The SANTAVAC efficacy and mechanism of action were described in 2009-2016 in series of scientific papers and summarized in the SANTAVAC concept - a scientific basis for the all SANTAVAC-based vaccines.

An important step in SANTAVAC development was the creation and use of allogeneic antigens. The patient's own biomateral is not used in allovaccine production (in contrast to autologic vaccines), which is a prerequisite to mass production of vaccines. It was demonstrated that the allogeneic composition slows the growth of endothelial cells with a tumor-vessel phenotype by 60-fold and was therefore named SANTAVAC (Santa – 'holy', in many languages, VAC – a common abbreviation for vaccine). To publish the vaccine composition, however, a scientifically acceptable abbreviation (a Set of All Natural Target Antigens for Vaccination Against Cancer) was created. Currently, SANTAVAC is available for the preparation of SANTAVAC-based vaccines (by mixing with different adjuvants) for testing in clinical trials.

History

2005-2006 – Study of cancer prevention problems and the search for possible solutions, design of experiments, development of the 'cell proteomic footprint' technology, and invention of the new method of vaccine preparation that gave rise to SANTAVAC preparation.
2006-2007 – First patent applications were filled.
2008 – Eurasian patents were granted.
2009 – Cell proteomic footprint technology was published (together with Bruker) .
2010 – Vaccine preparation, including SANTAVAC from the harvested cell surface antigens was published .
2010-2012 – Research revealed that cancer cells subjected to drug therapy cause selection pressures resulting in changes to their cell surface antigens allowing them to escape immune responses elicited by anti-cancer vaccination. Results of this study were published in 2012 (together with Bruker and Institute of Biomedical Chemistry) .
2010-2014 – Research on the preparation of antiangiogenic cancer vaccines based on SANTAVAC was extended.
2013-2015 – Publication of data primarily relating to autologous SANTAVAC development and publication of the SANTAVAC concept . European, Korean, China and Japan patents were granted.
2016 – Extending research on allogenic SANTAVAC preparation. Following the SANTAVAC concept, the "'miracle' efficacy of the allogeneic SANTAVAC" was demonstrated experimentally.
Publication of data related to allogeneic SANTAVAC efficacy . The name SANTAVAC was mentioned for the first time in scientific publication .
2017 – The trademark SANTAVAC was registered and a USA patent was granted.

Production

Cultures of human microcirculatory endothelial cells (from any source) are used to produce SANTAVAC. These cells are stimulated to express a tumor-vessel-specific profile comprised of surface antigens . It was demonstrated that the induction of this specific phenotype is possible by the culturing (in a specific way) the endothelial cells with conditioned medium collected from hepatocellular carcinoma cells . Endothelial cells then are treated with a highly purified protease (usually trypsin) which cleaves a set of antigens from the endothelial cell surface. The conditions for the protease treatment maintain cellular viability, i.e., the cell membrane is not damaged and the cellular content is not released. The antigens obtained using this approach are highly tumor-vessel specific and ready to be used in the production of cancer vaccines.

Animal models

Because the final SANTAVAC composition is a 'fine tuned' composition of human allogenic antigens collected using specific conditions from human microcirculatory endothelial cells with a tumor-vessel-specific phenotype, its efficacy cannot be confirmed in animals unless an animal-based SANTАVAC is first developed. Specifically, administration of SANTAVAC in animal models would represent a xeno-vaccination and would not facilitate the process resulting in the use of SANTVAC for human use. Animal models can only be used in preclinical trials to assess the safety of SANTAVAC, that is, in the context of adverse reactions potentially developing depending on the chosen adjuvant formulation.

SANTAVAC as a universal cancer vaccine

Because there is such a broad range of different solid tumors that can arise, a universal cancer vaccine would eliminate the need of developing separate vaccines for the each cancer type that would be both time consuming and costly. This makes the "development of a universal cancer vaccine attractive". Attempts to develop universal vaccines are not new . The most famous attempts were telomerase- and mucin 1-based vaccines. The activity of telomerase is necessary for the immortalization and growth of all tumors; therefore, vaccination against the catalytic part of telomerase (hTERT) is an example of the universal cancer vaccine . Overexpression of mucin 1 is also associated with many cancers and for this reason mucin 1 antigens were also considered as candidates in the "development of a universal vaccine" . Unfortunately, these attempts were not successful . Vaccination "using antigens expressed by endothelial cells lining the tumor vasculature" is one option for universal vaccination since it can prevent the any growing solid tumor which is pertinent to all cancers except for blood cancers (leukemia and lymphomas) that do not present as solid tumors

Funding

The development of SANTAVAC was funded Lokhov and coworkers and partially by Biobohemia LLC. Bruker self-funded portions of his research.
No state funds were used in the vaccine's development.

Trademark

The trademark SANTAVAC™ was registered with the International Register of Marks maintained under the Madrid Agreement and Protocol.
Registration number: 1 326 157 (registration date - September 12, 2016).
Basic registration: Russian Federation, 15.09.2016, 587249.
Designations under Madrid protocol: European Union, Japan, Republic of Korea, USA, China.

Patents

Lokhov P.G. "Method for producing an antitumoral vaccine based on surface endothelial cell antigens", 2007, Eurasian patent, №009327.
Lokhov P.G. Balashova E.E. "Method for testing cell culture quality", 2007, Eurasian patent, №009326.
Lokhov P.G. Balashova E.E. "Method for producing an antitumoral vaccine", 2009, Eurasian patent, №011421.
Lokhov P.G. "Method for producing an antitumoral vaccine based on surface endothelial cell antigens". Japanese patent №5154641. Date of registration December 14, 2012.
Lokhov P.G. "Method for producing an antitumoral vaccine based on surface endothelial cell antigens". Korean patent №10-1290641. Date of registration September 7, 2013.
Lokhov P.G. "Method for producing an antitumoral vaccine based on surface endothelial cell antigens". European patent №2140873, 2015 (Protection in Switzerland/Liechtenstein, Germany, Spain, France, the United Kingdom, Ireland and Italy).
Lokhov P.G. "Method for producing an antitumoral vaccine based on surface endothelial cell antigens". US patent №9844586. Issue date December 19, 2017.

References

This article "SANTAVAC" is from Wikipedia. The list of its authors can be seen in its historical and/or the page Edithistory:SANTAVAC. Articles copied from Draft Namespace on Wikipedia could be seen on the Draft Namespace of Wikipedia and not main one.

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