Vaccine and chemotherapy against pancreatic tumors
The only effective method of treating pancreatic duct adenocarcinoma is total surgical removal, after which approximately 80% of patients develop relapses leading to death within 5 years. Moreover, due to the absence of effector lymphocytes infiltrating the tumor zone, such neoplasms are non-immunogenic and do not respond to immunotherapy, which further limits the possibilities of treatment.
Researchers at Johns Hopkins University, working under the guidance of Dr. Lei Zheng, claim that the combination of therapeutic vaccine and low-dose chemotherapy, used before surgery, makes adenocarcinomas of the pancreatic ducts susceptible to immunotherapy.
In the period from 2008 to 2012, the authors conducted a clinical study involving 59 patients with pancreatic duct adenocarcinoma. The patients were randomly divided into 3 groups. One group received the therapeutic GVAX vaccine developed by the authors, the second group received GVAX in combination with a single intravenous injection of cyclophosphamide at a dose of 200 mg/m2, and the third group received GVAX in combination with oral administration of 100 mg cyclophosphamide once a day in the "week after week" mode.
Approximately 2 weeks after vaccination, all patients underwent surgical removal of the tumor. As a result of the operation, the tumor was completely removed from 39 of the 59 participants who subsequently underwent the standard protocol of chemo and radiotherapy. The tumors removed from them were subjected to histological analysis. For comparison, tumor samples were analyzed from 58 participants in other studies who either were not vaccinated or underwent vaccination after surgical removal of the tumor.
The analysis of tumor tissue showed that the combination of the vaccine with chemotherapy ensured the formation of lymphoid aggregates in the tumors of 33 out of 39 patients. The study of the composition of these aggregates revealed the prevalence of effector T-lymphocytes over regulatory T-cells. This means that the tumors have acquired immunogenicity, and the lymphocytes infiltrating them have the ability to destroy malignant cells. The severity of the shift towards effector cells correlated with better survival of patients.
The authors also found that tumors of patients who lived more than three years after vaccination were characterized by a higher activity of mechanisms that stimulate immune responses than tumors of patients who died less than 1.5 years after vaccination.
Currently, researchers are engaged in a more detailed study of the immune profiles of lymphoid aggregates formed in tumors as a result of vaccination. They hope to develop immunotherapeutic approaches that ensure simultaneous activation of "good" and suppression of "bad" immunoregulatory signals.
The article by Eric R. Lutz et al. Immunotherapy Converts Nonimmunogenic Pancreatic Tumors into Immunogenic Foci of Immune Regulation is published in the journal Cancer Immunology Research.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the American Association for Cancer Research:
A Vaccine May Cause Pancreatic Cancer to Respond to Immunotherapy.
20.06.2014