Immunotherapy has become a key aspect of cancer research in recent years, though there is still a lot of work ahead to truly unlock its full potential. Currently, a lot of research is focused on why certain types of cancers are seemingly not immunogenic and have poor response rates to different kinds of immunotherapy drugs. Other clinical trials are working to determine what types of immunotherapy drugs and combinations are most effective against the cancers that have already shown promising results with these treatments, like mesothelioma.
While researchers struggle to determine why certain cancers aren’t reacting to various immunotherapy drugs already developed, many have begun to focus on what could be the possible solution: personalized cancer vaccines. For years, researchers have believed the key to curing cancer is precision or personalized medicine, and many of these clinical trials so far have shown promise in bringing research that much closer to a cure.
How Personalized Cancer Vaccines Work
As the name implies, personalized cancer vaccines are created as a unique treatment for each individual patient. Though two people diagnosed with the same type and stage of cancer may often be recommended a similar treatment plan, researchers have found that tumors between individuals can actually differ greatly, even between those with the same diagnosis.
Tumors have been found to present a rather unique genetic makeup, specifically regarding the cancer cells’ antigens, molecules that can cause the immune system to create antibodies and react to a foreign agent in the body. In many instances, cancer cells produce antigens that mimic normal cells, which causes the immune system to ignore these toxic cells rather than react.
Researchers believe this concept is a major reason why some past immunotherapy clinical trials have failed. Doctors didn’t understand or focus on what antigens the tumors were presenting, which could lead to the immunotherapy drugs not being able to stimulate the appropriate immune system response.
With this in mind, researchers can make a personalized treatment by first biopsying an individual’s tumor to understand the genetic sequences of the tumor versus the patient’s healthy cells. These differences in DNA can range from a few to over 1,000 clear mutations. After understanding the antigens cancer cells and normal cells present at the individual level, cancer immunologists can determine which mutated antigens to target with a personalized vaccine.
Knowing which antigens to target, however, can be another obstacle researchers still need to overcome. Through previous research, doctors have noted that about only 3 or 5 out of every 100 mutations creates an antigen that can be targeted with treatment. While it is possible to make an effective vaccine with just one known antigen target, researchers have generally agreed that at least 20 antigens are needed to maximize the effects of the vaccine and achieve successful results. After determining the antigens to target, scientists can synthesize them into a vaccine that will then spur the immune system to attack the cancer cells.
Studies Showing Promise for Mesothelioma
So far, many of the clinical trials around personalized vaccines have only been among smaller groups of patients in earlier phased trials. Even so, several of these studies could provide hope for mesothelioma patients in extending survival and helping prevent cancer recurrence.
One study looked specifically at personalized vaccines for ten pleural mesothelioma patients. Researchers explored the application of dendritic cells, which naturally induce an immune response. The dendritic cells are able to process antigens and react by migrating to the lymph nodes and activating the body’s T cells against the patient’s tumor cells.
Though the trial involved a small group of patients, the results were promising and will hopefully lead to larger clinical trials in the near future. Seven patients were able to extend survival to at least 24 months, with two patients living beyond 50 and 66 months at their last follow up. In addition to longer survival, researchers found the treatment to be safe and tolerable for patients, with only a mild fever popping up as a side effect for some. Though the possibility of complete remission was unclear, the trial shows a step in the right direction for mesothelioma cancer patients.
Two other promising clinical trials studied the effects of neoantigen vaccines for melanoma patients. Researchers have already noted the genetic similarities between mesothelioma and melanoma, particularly the presence of the BAP1 gene. As such, researchers often can turn to treatments approved for melanoma to also treat or further research for mesothelioma. Since mesothelioma is so rare, continuing to better understand its similarities to other more common cancers like this can certainly help advance treatment options.
One of these melanoma clinical trials out of Dana Farber Cancer Institute in Boston studied the effect of personalized cancer vaccines for six patients who presented tumors with antigens that could be targeted with treatment. These advanced-stage skin cancer patients first underwent surgery, and after a period of recovery received their vaccines 18 weeks later.
While the patients experienced some mild side effects, patients were able to achieve prolonged survival. Four patients achieved no disease recurrence after 25 months, and the other two were also able to achieve remission after undergoing another type of immunotherapy when the disease first recurred. Another similar trial out of Germany tested vaccines on 13 melanoma patients, with eight subjects still in remission 12 – 23 months after treatment. Average survival for mesothelioma patients is only 12 – 21 months and recurrence is frequent, so it is hopeful that a similar trial can be adopted for those with this rarer cancer.
Continued Immunotherapy Research
Cancer immunotherapy research has already made great progress for a number of different cancers and may continue to extend its success with further study. Currently, some researchers are even looking at the potential of adopting these vaccines into a preventive measure to fight off cancer mutations and the development of tumors.
Molecular testing and precision medicine continues to be a driving trend in cancer care, and researchers hope that these treatments could eventually lead to a cure.