Sorrento Therapeutics, Inc. announced it has been working on a novel decoy cellular vaccine for COVID-19 (STI-6991) and is in active discussions with the FDA’s Center for Biologics Evaluation and Research under IND#019724 regarding the required IND-enabling studies, CMC (chemistry, manufacturing and controls), clinical protocol and end-points for potential accelerated approval. Upon receiving guidance from the FDA, Sorrento intends to submit a full package for an IND filing that would enable human clinical trials to start as soon as possible.
The decoy cell strategy (I-Cell™, which means immune-training cells) has been conceptualized and developed by Sorrento scientists utilizing expertise acquired in the fight against cancer. Sorrento expects to utilize a well-known replicating cell line (human erythroleukemia, K562) to incorporate SARS-CoV-2’s spike protein or its S1 domain onto the cellular membrane so that the viral antigen is presented on a decoy cell surface to elicit both T cell and B cell immunities. The selected cell line has been used safely in cancer vaccination programs and is well characterized (clinical trials using K562 expressing granulocyte-macrophage colony-stimulating factor have been used as a tumor vaccine). Upon expression of the viral protein as a surface marker, the decoy cell “looks like” the virus to a healthy person’s immune system. After irradiation to prevent the replication of the cells, the cells can be administered by intramuscular injection as a vaccine. In the presence of this “look alike” training cell, the recipient may develop a protective immune response and produce corresponding neutralizing antibodies against the SARS-CoV-2 virus. If the vaccinated subject is later exposed to the SARS-CoV-2 coronavirus, his or her T cell immunity and neutralizing antibodies are expected to block the spike protein from attaching to the ACE2 (angiotensin converting enzyme 2) on the normal human cell surface, thus potentially attenuating or preventing the SARS-CoV-2 infection which causes COVID-19 disease.
A short communication explaining this vaccination approach was accepted for publication by Medicine in Drug Discovery (an Elsevier peer reviewed open access journal. The article can be found at https://www.sciencedirect.com/science/article/pii/S2590098620300130?via%3Dihub). Per the publication, “the overall strategy to utilize a viral antigen-expressing, non-replicating cellular system as both a carrier, and as an immunogenic antigen-presenting platform is novel. The view is that this platform will be recognized by the immune system, and a neutralizing antibody response will ensue. The most important aspect of the platform is that it should allow for dendritic cells to recruit T lymphocytes and induce Th1 cell polarization that if feasible will also induce a cytotoxic T cell response and thus clearance of SARS-CoV-2 virus. The strategy should be safe as they are using K562 cell line that is HLA negative. The platform appears to be readily scalable and would appear to provide uniform cell product. One key aspect is that will the vaccine prevent engraftment and proliferation after host implantation; the answer here appears to be yes as the cells will be irradiated post-expansion in order to abolish their replication ability and thus no in vivo cell growth. In sum an intriguing platform is put forth and if viable as it appears to be it could make an impact on the treatment of COVID-19.”1
Sorrento is currently working to demonstrate I-Cells’ ability to generate protective T cell and B cell immunities in an animal model. Sorrento has identified a leading infectious disease contract research organization to support the phase 1 clinical trial and accelerated timelines. Sorrento has begun process development, validation and scaled up manufacturing testing in its state-of-the-art cGMP cell therapy facilities in San Diego in anticipation of registrational clinical trials and commercialization.
Sorrento anticipates all IND requirements will be fulfilled in the next few months. Depending on government support and the FDA’s response, Sorrento believes it may be in a position to initiate human vaccination trials as early as mid-year 2020.
David Epstein, former CEO of Novartis Pharmaceuticals, a division of Novartis AG, who has been advising Sorrento, said, “This promising vaccination strategy is uniquely suited for rapid scale up and advancement into the clinic. I am hopeful because this novel approach can make a difference in the lives of so many.”
“We have developed a novel approach to vaccination that we believe can be a breakthrough in the fight against COVID-19. We believe using a human cell as a training agent is unique and likely to be effective for vaccination,” stated Dr Henry Ji, Chairman and CEO of Sorrento Therapeutics. “By utilizing an existing cell line that has previously been used to make cancer vaccines, we know we have a product candidate with a promising safety profile. We are very confident that, if our product candidate is approved, we will have the required capacity in place to produce enough doses to protect millions of people in the near term. Confirming that I-Cell works in humans is our top priority and our most immediate focus.”