Intra-tumoral injection of vaccines, viruses and vaccine adjuvants
There are numerous techniques to stimulate an immune response into a tumor. It has been noted that in certain cases vaccines intended to prevent other illness may inadvertently stimulate an immune response within cancer. Myers, et al. published in March 2005 an article “Oncolytic activities of approved mumps and measles vaccines for therapy of ovarian cancer.” They state: “In this study we demonstrated that two commercially available paramyxoviral vaccines, Moraten measles and Jeryl Lynn mumps have promising anti-tumor activities against human ovarian xenografts established in the peritoneal cavities of immunodeficient mice.” Galanis, et al., also from Mayo, published January 2015 in Cancer Res that the use of the Edmonston vaccine strain of the measles virus showed effectiveness in the treatment of ovarian cancer, in patients who had previously received extensive chemotherapy, extending survival to 26.5 months in a group of 16 patients. Msaouel, et al., also from Mayo, reported anti-tumor activity with the same Edmonston measles vaccine. I might add that this is the old version of the measles vaccine.
Curiously, about the time of some of these publications, these vaccines have become hard to find, and it seems their sale in the U.S. has been blocked, as now everything has shifted to the use of the MMR in place of the older vaccine. I won’t speculate the coincidence of the timing of this. As you see from the study, the results are not perfect, but I am sure the success can be increased with the combined use of other immunotherapy agents.
In July of 2018, Mckenzie and Nichols published in JAMA Dermatology a study in which a 97-year old woman with squamous cell carcinoma of the skin was treated successfully with a series of injections of Gardasil, the HPV vaccine. They initially injected the patient in the arm, to initiate an immune reaction, and then followed up with injection into the tumor. They noted that non-treated lesions resolved as well. There are numerous viruses or viral-based gene therapies that can be injected into tumor and can stimulate an immune response. Like most treatments, the use of these alone is probably not enough to generate a cure in most patients, but this can probably be significantly improved when used with the right combination of immunotherapy agents.
It is also reasonable to mention that, just like in vaccines, for the combination of immunotherapy agents to be effective, they often need a carrier agent, known as a vaccine adjuvant. This can be a key aspect to generating an immune response. In our work, we use Montanide ISA 51 or Saponin-based vaccine adjuvants, sometimes with a gel delivery. The idea is not only to enhance antigen delivery to the immune cells, but also to create a slow release formulation, keeping the medicines in the tumor environment. Montanide ISA 51 is used in several vaccines as an adjuvant because it is a water and oil-based mixture that enhances antigen delivery. It seems that the oil can solubilize some of the medications and create a slow release delivery system.
Another promising intra-tumoral therapy involves the use of a gene therapy that causes the increased production of Interleukin 12 within the tumor. IL-12 can activate both natural killer cells (NK) and attacking (cytotoxic) T cells. Studies are being done to inject the gene in a plasmid within the tumor. In addition, the gene can be placed within a virus and injected into the tumor. In this case, both the virus itself and the increase in production of IL-12 can stimulate an immune response against the cancer.
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