NEW FORMULATION OF RECOMBINANT ANTITUMOR VACCINES BASED ON SECRETORY GRANULES FOR SUSTAINED RELEASE

CANCER IS A MAJOR CAUSE OF DEATH WORLDWIDE IN BOTH MEN AND WOMEN. THE MAIN PROBLEM IN ITS TREATMENT LIES IN RELAPSES AFTER RESECTION OF THE PRIMARY TUMOR AND/OR CHEMOTHERAPY. THIS SITUATION HAS PROMPTED, IN RECENT YEARS, THE SEARCH FOR STIMULATION OF THE IMMUNE SYSTEM WITH ANTITUMOR ACTIVITY THAT ALLOWS PROLONGED ANTITUMOR CONTROL OVER TIME, THUS COMPLEMENTING CONVENTIONAL TREATMENTS. UNFORTUNATELY, VACCINES WITH ANTITUMOR ACTIVITY ARE NOT SUFFICIENTLY EFFECTIVE BECAUSE THERE IS NO ROBUST ANTITUMOR RESPONSE. THIS IS DUE TO SUBOPTIMAL FORMULATIONS, WITH LOW EXPOSURE AND BIOAVAILABILITY OF TUMOR ANTIGENS, WHICH USE ADJUVANTS WITH LITTLE EFFICIENCY. RECENT ADVANCES HAVE JUST DEMONSTRATED A RADICAL INCREASE IN THE EFFICACY OF VACCINES BASED ON ANTIGENS THAT ARE RELEASED PROGRESSIVELY OVER TIME. THESE RESULTS THUS INDICATE THE NEED TO DEVELOP NEW FORMULATIONS THAT ALLOW PROLONGED ANTIGENIC EXPOSURE, OVER WEEKS, WITHOUT THE NEED TO RESORT TO DAILY INJECTIONS. SECRETVAC WILL DEVELOP A NOVEL THERAPEUTIC CONCEPT IN ONCOLOGY BUILT ON PROMISING DATA FROM THE PREVIOUS PROJECT (PID2019-105416RB-I00), AND BASED ON OUR NEWLY PATENTED TECHNOLOGY OF SECRETION GRANULES (EP19382271.5). THIS TECHNOLOGY DEVELOPS CHEMICALLY HOMOGENEOUS AND PURE PROTEIN-SECRETING MICRO-GRANULES, WHICH UNDER PHYSIOLOGICAL CONDITIONS SLOWLY RELEASE MULTIVALENT PROTEIN NANOPARTICLES. THEREFORE, SUCH RELEASED MATERIAL, IF IT IS MADE UP OF ANTIGENS, WILL BE EXPOSED AND WILL STIMULATE THE PATIENT'S IMMUNE SYSTEM FOR DAYS OR WEEKS. THIS TRANSVERSAL TECHNOLOGY, BASED ON A REGULATORY-FRIENDLY, BIOCOMPATIBLE, AND BIODEGRADABLE MATERIAL, MAY BE ESPECIALLY ATTRACTIVE FOR THE SLOW RELEASE OF TUMOR ANTIGENS, THEIR OPTIMAL IMMUNOGENIC PRESENTATION, AND THE CONSEQUENT STIMULATION OF THE IMMUNE SYSTEM, SINCE IT ALLOWS: A) TO FORMULATE ANTIGENS OF GREAT MOLECULAR SIZE THAT T CELLS MOBILIZE, B) PRESENT MULTIVALENT ANTIGENIC NANOPARTICLES THAT WILL ENHANCE THE IMMUNE RESPONSE, C) INCREASE ANTIGEN EXPOSURE DUE TO ITS SLOW DISPOSITION AND D) INCREASE THE STABILITY OF THE PROTEIN AGAINST DEGRADATION, WITH WHICH ITS EFFECT WILL BE DURABLE. FURTHERMORE, IN PRELIMINARY RESULTS WE HAVE OBSERVED THAT ANTIGENS FORMULATED AS SECRETION GRANULES ARE CAPABLE OF STIMULATING THE INNATE IMMUNE RESPONSE COMPARED TO THE SAME PROTEIN IN SOLUBLE FORMAT; THAT IS, THEY ACT PER SE AS AN ADJUVANT. IN A THERAPEUTIC CONTEXT, THE DEVELOPMENT OF THIS ANTITUMOR VACCINE PLATFORM IS EXPECTED TO ACHIEVE MORE EFFECTIVE PRODUCTS THAN CURRENT ONES FOR INDIVIDUAL USE OR IN SYNERGY WITH CONVENTIONAL TREATMENTS. THESE PRODUCTS WOULD BE APPLICABLE WITHOUT THE NEED FOR ADJUVANTS OR REPEATED ADMINISTRATIONS, WOULD BE BASED ON CHEAP, SIMPLE, CONTROLLABLE AND SCALABLE PRODUCTION, AND WOULD HAVE A CHEMICALLY HOMOGENEOUS AND BIOCOMPATIBLE COMPOSITION. THE SUCCESS OF THIS PROOF OF CONCEPT WOULD BE TRANSFERABLE TO OTHER HUMAN AND VETERINARY VACCINE PROBLEMS AND PATHOLOGIES NOT NECESSARILY RELATED TO CANCER, SINCE THE PRINCIPLE OF THE TECHNOLOGY AND THE SCIENTIFIC CONCEPTS THAT SUPPORT IT ARE FULLY TRANSVERSAL.