The Biggest Step Toward a Cure for a Patient with Metastatic Cancer

In recent years, genetics has left us almost intoxicated by witnessing incredible advances in cancer treatment. Treatments targeting metastasis, meaning cancer spreading to other organs, are among the foremost developments. Using next-generation gene sequencing methods, researchers have succeeded in developing personalized cancer vaccines. Let us explore vaccines that could revolutionize cancer treatment.

Cancer cells have the ability to undergo continual mutation . These mutations cause them to begin producing neo-antigens , tumor molecules that the immune system has not previously detected . These tumor molecules are recognized by our immune system’s T cells, creating an immune response. This contributes greatly to the effectiveness of current immunotherapies . However, when a tumor has too many mutations, immunotherapy effectiveness decreases. In other words, an immune response is generated against only a small number of mutations. Most mutations occurring in cancer are also individual-specific. Thus, a single tumor in the same patient contains cells with different genetic structures. Personalized approaches therefore gain importance. For this purpose, personalized cancer vaccines suited to the patient’s tumor structure are being developed.

Personalized Cancer Vaccines: Mutanome Vaccines

The most important advantage of genetic tests is that they reveal the molecular structure of a patient’s tumor in detail. A similar method is followed in developing personalized cancer vaccines. Samples are taken from the patient’s tumor tissue, whole-exome sequencing and RNA sequencing are performed. Whole-exome sequencing involves examining only genes responsible for protein production, identifying regions directly influencing cancer development. The patient’s healthy cells are then sequenced for comparison. All these differences are used to create “personalized vaccines.” These vaccines are also called mutanome vaccines .

The underlying principle of personalized cancer vaccines is:

Designing a vaccine suited to the genetic structure of the patient’s tumor, thereby generating an effective immune response.

The first clinical applications of personalized cancer vaccines in humans have been carried out.

The first study was conducted in Germany by Turkish scientist Özlem Türeci and her team. Patients with stage 3 and 4 melanoma (skin cancer) were enrolled: 13 patients underwent exome sequencing and vaccination suited to their genetic structure. According to the research results:

• All patients showed an immune response against tumor antigens after vaccination.
• In 8 patients with evident tumor lesions during vaccination, no recurrence occurred for up to 2 years. Of 5 patients with recurrent metastatic cancer, 2 showed an immune response. The second study was conducted at Harvard University’s Dana Farber Cancer Institute.

In a study of patients with malignant melanoma skin cancer, a vaccine was developed against “20 neoantigens” obtained from their tumor profiles. Of 6 vaccinated patients, 4 had no recurrence for 25 months. The other 2 patients with recurrent cancer received immunotherapy drugs after vaccination, and tumor growth regression was observed.

It is important to emphasize that these are the first studies testing the vaccine’s efficacy. However, the results are very promising.

What Do These Results Mean for Cancer Treatment?

• Advances in genetics have begun to accelerate the discovery of personalized medicines.
• These studies represent the first human applications of “personalized” cancer vaccines.
• Such vaccines may prevent recurrence in high-risk patients.
• Combinations of personalized vaccines and immunotherapy drugs may offer effective treatment in the future.
• Personalized vaccines offer an effective treatment option against cancer cells with very high mutation rates, generating an effective immune response against cancer cells.

Readers will immediately think of the Cuban lung cancer vaccine and wonder whether the vaccine discussed here differs from Cuban cancer vaccines. Personalized cancer vaccines, compared with Cuban cancer vaccines frequently discussed in recent years and unfortunately marketed in a manner we disapprove of, almost as trading in hope, are very different and appear more effective according to these early clinical studies. Personalized vaccines are designed according to the genetic profile of the patient’s tumor. Cuban cancer vaccines try to generate an immune response against a single antigen. In contrast, personalized cancer vaccines can generate an immune response against thousands of tumor antigens, producing a stronger response specific to the patient’s cancer.