Immunotherapy medications such as ipilimumab, nivolumab, and pembrolizumab have greatly improved survival in people with advanced melanoma. However, many people with advanced melanoma have tumors that are resistant or become resistant to these immunotherapies as well as to targeted therapies. Innovative treatments are needed.
An option that is being explored by researchers and supported by MRA is personalized cancer vaccines. Although some vaccines such as the flu vaccine and the COVID-19 vaccine are meant to prevent a disease, vaccines can also be therapeutic and are being investigated to treat cancer that has already been diagnosed and to keep it from coming back. MRA has funded several cancer vaccine studies, including a Team Science Award that was granted to Dr. Patrick Ott of the Dana-Farber Cancer Institute in Boston, MA and his colleagues. Personalized cancer vaccines are custom-made for each patient. Dr. Ott is a pioneer in the development of a personalized cancer vaccine called NeoVax.
Over time, cancer cells develop mutations in their DNA that allow them to survive. These mutations generate abnormal proteins that the immune system will recognize as foreign. The strategy of personalized cancer vaccines takes advantage of the fact that these new, abnormal proteins (called neoantigens) are only present in the tumor and not the rest of the patient’s body.
To make the customized NeoVax cancer vaccine, first the patient’s melanoma is obtained with surgery. Then, the DNA from the tumor is examined to find mutations, and up to 20 mutant proteins (neoantigens) that are most likely to be recognized by the immune system as foreign are identified and used to create the NeoVax vaccine.1 The vaccine is then injected into the patient. The neoantigens in the vaccine activate the immune system, which mounts an attack against tumors throughout the patient’s body without attacking healthy cells.
Another approach to cancer vaccines uses technology similar to that used to produce mRNA vaccines against COVID-19. For this, an mRNA vaccine is created that produces the abnormal neoantigens specifically for that patient. A different strategy that is not personalized involves vaccination with fat-coated proteins or mRNA that generates proteins commonly found in most melanomas.
Cancer vaccines, both personalized and not, are being tested in clinical trials, often in combination with an immune checkpoint inhibitor to further enhance the immune response. Overall, personalized vaccines are safe, are tolerated well by patients, and destroy the tumors.2 Importantly, the anti-tumor immune response and tumor control are long-lasting, around 4 years with NeoVax.3 Below we share a patient’s journey that illustrates the promise of NeoVax to treat advanced melanoma.
In 2007, after watching a mole on her calf change, Debbie Likes visited her primary care doctor who removed the mole and later told her that it was a melanoma. An initial sentinel lymph node biopsy was negative, and Debbie was relieved. However, a few years later, she had a recurrence of melanoma in two areas of her arm. After surgery to remove the tumors, Debbie underwent a year of interferon therapy, which had severe side effects. Unfortunately, her melanoma recurred three additional times beginning in 2011.
Around 2013, Debbie became one of Dr. Ott’s patients. Dr. Ott suggested that Debbie consider a clinical trial testing a personalized vaccine called NeoVax to treat her melanoma. Although Debbie had concerns about unknown side effects, she decided to enroll in the trial. After her first injection of NeoVax in the trial, Debbie developed large welts on her abdomen and mild flu-like symptoms. These side effects improved with each dose of the vaccine. She had about 7 doses of the vaccine over a span of about 5 months. At the end of the trial, her scans still showed melanoma. Debbie had surgery and radiation, and then finally achieved “No Evidence of Disease (NED),” which means a complete response or remission. Today, she does not receive any treatments for her melanoma. Debbie has scans every 6 months and has been NED for 7 years.
Debbie encourages other patients considering NeoVax to “do it!!” She urges other patients to not quit and to try to stay positive even though it is difficult. Debbie would like researchers to know that an experimental treatment like this is scary for the patient because they don’t know what to expect and for the patient’s caregiver, who often feels helpless. But in the end, she is grateful to have been part of the NeoVax clinical trial.
An encouraging result from a Phase 1 trial of NeoVax is that immune cells were detected that recognized neoantigens that were not present in the original vaccine. This suggests that in the presence of the vaccine, the immune system can mount a response against components of the tumor that were not in the vaccine, potentially leading to a broader, more robust anti-tumor immune response.3 Dr. Ott and his team are continuing to perform clinical trials to investigate NeoVax in combination with drugs that further activate the immune system (NCT03929029, NCT04930783).
Challenges with cancer vaccines remain:
MRA continues to support studies investigating therapeutic vaccines for melanoma.
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