Autologous Cancer Vaccines in the Era of Personalized Medicine
Within each of our cells are the instructions for creating life: DNA. This macromolecule is the foundation of every living being, and the smallest changes in its composition creates the wide diversity of life we see on the planet, both between species (dog vs. human) and between individuals (you vs. the stranger sitting next to you on the train).
Underlying this individuality that DNA bestows upon us is also a plethora of similarities between organisms. For instance, we humans share about 84% of our DNA with dogs. This doesn’t mean we are 84% canine–rather, only about 16% of our DNA codes for all the physical differences we see between humans and dogs.
Interestingly, these genetic similarities and differences are also true for cancer. Tumors of any cancer type express antigens on the surface of their cells as a result of different mutations. These mutations that rise to cancer antigens can be either universal to a single cancer type, or unique to an individual tumor. For example, a Glioblastoma in one individual may share only 30% of its mutations with a Glioblastoma from a different individual, so 70% of that tumor’s antigens will be unique to the person with the tumor.
Researchers have taken advantage of this knowledge to create immunotherapies that utilize all those tumor antigens to create a personalized treatment. Autologous cancer vaccines (ACVs) are one such immunotherapy, created from a patient’s own tumor and administered back to that individual to stimulate an immune response against all the tumor’s antigens, both unique and universal.
How do ACVs work?
Whole-cell autologous cancer vaccines are made from a patient’s tumor following its surgical resection. The tumor is broken down into individual cancer cells which are then rendered replication-defective, but kept intact. These cells are then suspended in a solution and administered to the patient via injection, often with an adjuvant.
Since the vaccine contains whole tumor cells, the antigens expressed on the surface of those cells remain structurally untouched. Thus, when exposed to the patient’s bloodstream, the tumor antigens stimulate a T cell-based immune response against the cancer.
Safety of ACVs
In a meta-analysis of 14 human clinical trials of ACVs ranging from 1977 to 2020, the administration of ACVs were well-tolerated, with no deaths resulting from the treatment and a low incidence of high-grade adverse events (Bastin et. al, 2023). The most frequently reported adverse event in these studies was redness and itching of the skin at the injection site.
Efficacy of ACVs
In the same review mentioned above, efficacy of ACVs following surgical resection of solid tumors in humans was examined. Metrics used included overall and complete response of the cancer to the vaccine (overall = decreased size or growth of tumor, complete = disappearance of cancer), and overall and disease-free survival. While the data was too limited to provide any meaningful deductions for overall response of the cancer to treatment, ACVs were associated with an increase in overall survival compared to controls (Bastin et. al, 2023).
Recent Advances in ACV Technology
More clinical trials are being approved to test the efficacy of new ACVs. Following the formation of Biovaxys Technology Corp in 2018, the company’s ACV (BVX-0918) was approved for phase I clinical trials for the treatment of Stage III/IV ovarian cancer (Berd, 2023). More recently in March 2024, PhotonPharma’s ACV (Innocell) was approved to begin clinical trials (PR Newswire, 2024).
While ACVs have been studied for over 30 years, few are available commercially outside of clinical trials. In 2010, Sipuleucel-T / Provenge became the first (and currently only) autologous cancer vaccine in the US approved by the FDA for treating prostate cancer.
Reasoning behind this lack of commercialization includes certain challenges such as the need to create individual vaccines for each patient, as well as the need for a consensus on the clinical efficacy of ACVs in the scientific community in the wake of promising survival and immune response data. Another delay to vaccine licensure is the lengthy timeline of clinical trials in the human market, in which it may take as long as 15 years for a therapy to pass all stages of a clinical trial.
Applications of ACVs to Veterinary Oncology
Due to the high genetic and immunological similarities between humans and animals, treatments for diseases like cancer are often tested on companion animals like dogs, cats, and horses before trickling into human health. Moreover, those treatments that prove efficacious in companion animals become staples of treatment in the veterinary health industry. Few ACVs are available for use in humans and animals, but due to the promising data of clinical trials they are becoming more popular in the veterinary space.
At Torigen, we are making strides in ACV technology. We create a personalized vaccine with a unique MIM-SIS adjuvant for companion animals that is available for commercial sale for any type of solid tumor.
Currently in the veterinary market, autologous cancer vaccines are experimentally labeled, yet available for sale as regulated by the USDA department of Center of Veterinary Biologics. With more time and additional studies, the goal is to have multiple approved autologous cancer vaccines on the market.
Conclusion
The traditional era of “one size fits all” treatments of disease is slowly being displaced by individualized medicine, in both human and veterinary health markets. The scientific community now recognizes the importance of personalization in treating diseases, especially cancer. These ideas are exemplified by ACVs, a truly personalized approach to the treatment of cancer in humans and animals.
References:
Bastin et. al. “Safety and efficacy of autologous cell vaccines in solid tumors: a systematic review and meta-analysis of randomized control trials.” Sci Rep. 2023 Feb 27;13(1):3347. doi: 10.1038/s41598-023-29630-9. PMID: 36849805; PMCID: PMC9971202.
Berd D. Portrait of an autologous cancer vaccine: Then and now. Hum Vaccin Immunother. 2023 Dec 31;19(1):2172925. doi: 10.1080/21645515.2023.2172925. Epub 2023 Feb 8. PMID: 36755486; PMCID: PMC10012894.