Preliminary data from a first-in-human study of an experimental messenger RNA immunotherapy (mRNA-4359), one of several cancer vaccines in clinical trials worldwide, were presented Saturday at the Oncology Congress in Barcelona.
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Sponsored by the American laboratory Moderna, the study showed that the therapy, which targets patients with lung cancer, melanoma and other solid tumors, “is well tolerated, without serious side effects, and can stimulate the body’s immune system to treat the cancer more effectively,” said the head of the trial in the United Kingdom, Dr. Debashis Sarker of King’s College London. “It is still too early to say how effective this treatment might be for people with advanced cancer,” he said.
1. What other advances?
Research on therapeutic anti-tumor vaccines has a relatively long history, but without significant success on a large scale so far. Dozens of clinical trials are underway, but how many will have conclusive final results after being tested in randomization on a significant number of patients?
Currently, the most advanced experimental therapeutic vaccine, Tedopi, is being developed by French biotech OSE Immunotherapeutics in patients with advanced non-small cell lung cancer. Tedopi is also being studied at an earlier stage (phase 2) in pancreatic cancer and ovarian cancer.
“Therapeutic vaccines are designed to treat existing cancer rather than prevent it from occurring.”
In patients with head and neck cancer, phase 2 clinical trials are being conducted on an mRNA vaccine from the German biotech company BioNtech and on an individualized vaccine therapy (TG4050), the flagship product of the French company Transgene.
The American laboratory Moderna hopes that its therapeutic vaccine against skin cancer, currently in trials, will be approved as early as 2025.
Immunotherapy is also on the rise
This is one of the major advances in recent years in cancerology. Immunotherapy confirms its benefits in the face of a growing number of cancers, in particular “triple negative”, a particularly serious and resistant form of breast cancer. The greatest international specialists currently meeting in Barcelona are highlighting this therapeutic technique considered “revolutionary”. Immunotherapy no longer consists of acting on the cancer cell itself, but of stimulating the patient’s immune system to get it to fight against tumors.
At the annual congress of the European Society of Medical Oncology in Barcelona, medical specialists and researchers are highlighting a treatment that has already shown promising results for lung and skin cancers (melanoma) and that improves long-term survival in many other tumors. This is the case, for example, in triple-negative breast cancer. Particularly aggressive, it affects around 9,000 women each year, often young. It is particularly difficult to treat, in particular because it does not respond to the administration of estrogen or progesterone, the basis of other treatments commonly used in other forms of breast cancer.
But immunotherapy plus chemotherapy, a combination given before and after surgery, improved long-term survival in patients with triple-negative cancer, according to a study to be presented yesterday. The five-year overall survival rate was 86.6 percent in patients who received immunotherapy and 81.7 percent in the placebo group, according to the study.
2. How do these vaccines work?
Therapeutic vaccines are designed to treat existing cancer rather than prevent its occurrence. They are a mainstay of immunotherapy.
“The goal of a therapeutic cancer vaccine is to obtain a cellular immune response capable of destroying tumor cells while preserving healthy tissues,” explains Olivier Lantz, head of the clinical immunology laboratory at the Curie Institute. “We educate the immune system to recognize tumor cells” to eliminate them, he adds.
These vaccines target mutations (neoantigens) in the cells that make up tumors. But decoding all possible mutations is a long-term task, which complicates the development of therapeutic vaccines against cancer.
mRNA is one method for teaching the immune system to recognize these neoantigens to fight the tumor, but researchers also use viral vectors or peptides.
3. Generic and personalized vaccines
There are two main categories of therapeutic anti-cancer vaccines: generic vaccines for a given tumor type and personalized vaccines adapted to each patient.
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Generic vaccines target antigens common to different individuals that are expressed in the same way by tumor cells. Personalized vaccines target antigens that are unique to each tumor and each patient. They are complicated and expensive to manufacture.
