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Vaccine therapy: educating the immune system

Céline Giustranti
A vaccine involves educating the immune system to recognize an assailant in the body, and to reject it via an antigen. The best-known vaccines are preventive: they are administered to healthy individuals to prevent a pathology (e.g.: BCG against tuberculosis, tetanus, etc.).

Preventive vaccines against cancer

Ideally, they would prevent cancer from developing. This approach is possible as long as its origin is a viral infection. This is true of cervical cancer, which occurs due to an infection by the human papilloma virus. Vaccinating young girls between the ages of 11 and 14 would help prevent 70% of infections that lead to cancer. Certain types of liver cancer also occur after an infection by the Hepatitis B virus. Systematic vaccination against hepatitis B has largely helped to prevent liver cancer in parts of the world where the infection rate from the hepatitis B virus is high. To date, these are the only two examples of preventive vaccines against cancer.


Therapeutic vaccines against cancer

Therapeutic vaccination involves stimulating an immune response when it is absent in a patient suffering from cancer or with a high risk of recurrence. “It is very different from preventive vaccination, since the intruder is already present in the body, and the defenses are often overwhelmed by the proliferation of the tumor or slowed down by control mechanisms,” explains the immunologist Vassili Soumelis. Activating the immune system requires, first of all, that it recognizes the intruder, and secondly, that it considers it dangerous.

This system is based on the identification of a specific fragment of the cancer cell, a tumor antigen which, like bait, will help guide the immune system to the tumor cells. There are several options for “introducing” this antigen to the immune system.

  • Injecting a synthetic copy of the tumor antigen, possibly “boosted” by a molecule known as an adjuvant, capable of stimulating the immune response.
  • Injecting dendritic cells differentiated from the patient’s blood cells, mature and loaded with tumor antigens to stimulate the T lymphocytes.
  • Injecting laboratory-modified viruses to produce tumor antigens.

Whatever the option, the principle is based on the production of antibodies by the B lymphocytes (humoral response) or activation of the T lymphocytes (cellular response), which react specifically against tumor cells.

These types of active immunotherapy approaches have already proven effective. Sipuleucel-T was even the first vaccine to obtain market authorization in the United States to treat certain types of metastatic, hormone-resistant prostate cancer. It involves injecting “boosted” dendritic cells.

Many vaccine strategies using other tumor antigens are currently being studied.

Anti-cancer vaccines may take a variety of forms. For the moment, they can only be used if the cancerous cells are sufficiently different from the body’s cells to be recognized and if the immune system has not been too suppressed to react.

Developing even more targeted vaccines is the goal of the clinical trial launched by Dr Delphine Loirat and Eliane Piaggio in 2016. Its aim is to identify the antigen that is most specific to the tumor, meaning one that has resulted from a mutation of a specific gene in the tumor cell (one characteristic of tumor cells being that they accumulate mutations within their genome). This is what immunologists call a neoepitope. Neoepitopes make it possible to develop vaccines tailored for each patient, specific enough to trigger a response against the tumor with little toxicity to healthy tissues.