Two-stage immunotherapy for ovarian cancer
In most cases, ovarian cancer is detected at late stages and does not respond to existing treatment methods. Researchers at the Perelman School of Medicine, part of the University of Pennsylvania, have demonstrated that the two-stage immunotherapy they developed triggers a selectively acting antitumor immune response.
The authors were prompted to develop such a vaccine by an observation made in 2003 by one of the leaders of the work, Dr. George Koukos, who demonstrated that women whose tumors are infiltrated by T-lymphocytes live longer than patients whose tumors do not contain these cells. This and subsequent observations indicated that the immune system is trying to fight the disease, but cannot develop an immune response of sufficient strength.
As part of the latest work, the researchers subjected six patients with advanced ovarian cancer to two-stage immunotherapy, consisting in the introduction of a vaccine based on their own dendritic cells. Tumors progressed in all participants of the study, despite the standard chemotherapy.
At the first stage of the work, the scientists prepared for each of the patients a concentrate of dendritic cells isolated using apheresis, a process usually used to obtain donor platelets or other blood cells. After that, an extract of tumor tissue obtained during surgical removal of the neoplasm was added to the suspension of dendritic cells. The dendritic cells that "got acquainted" with the enemy in this way were injected back into patients who were simultaneously receiving a combination of chemotherapy drugs.
In the body, dendritic cells act as "conductors", guiding the actions of other cells of the immune system, directing them to fight an infectious agent or tumor.
After the introduction of the experimental vaccine, four out of six patients developed a pronounced antitumor immune response, which indicated the effectiveness of the approach. In one of the patients, the tumor was completely surgically removed and at the time of the introduction of the vaccine, she had no signs of the disease. This woman still remains in remission 42 months after the introduction of the vaccine. The other three patients who responded to treatment had signs of residual disease and were included in the second stage of the study.
At this stage, T-lymphocytes were isolated from each of the women, which were cultured in the laboratory until a population was obtained, the number of which was many times higher than the original one. The resulting cells were injected back into patients who had completed a course of chemotherapy, which destroyed the lymphocytes preserved in the body. In two of them, the injected T-lymphocytes, already "trained" by dendritic cells to fight the tumor, re-launched the antitumor immune response. As a result, one of the women went into remission, while the other had a stable course of the disease.
The authors note that it is still too early to talk about the effectiveness of the proposed approach, but the first results are very encouraging. Firstly, they demonstrated the safety and good tolerability of therapy. Secondly, both stages of treatment brought positive clinical results.
To date, a larger clinical trial of the developed method has already been launched, in which 25 women are already participating. The plans for the near future are to attract another 30 patients.
Article by Lana E. Kandalaft et al. Autologous lysate-pulsed dendritic cell vaccination followed by adaptive transfer of vaccine-primed ex vivo co-stimulated T cells in recurrent ovarian cancer is published in the journal OncoImmunology.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the University of Pennsylvania School of Medicine:
Two-Step Immunotherapy Attacks Advanced Ovarian Cancer, Penn Medicine Researchers Report.
04.02.2013