A microbiome based model of anticancer intervention

• Published in: European journal of cancer (1990) 2016-12, Vol.69, p.S151-S151
• Main Authors: Jimeno, J, Perezagua, C, Taboada, M, Sempere, L, Moscoso, J, Martinez, M, Gutierrez, J.R, Torres, J, Santo Tomas, J, Guardia, M.J, Rossell, E
• Format: Article
• Language: English
• Subjects: Bacteria; Cancer; Cancer therapies; CTLA-4 protein; Disease control; Dysbacteriosis; Endometrium; Esophagus; Glioblastoma; Hematology, Oncology and Palliative Medicine; Immunity; Intervention; Intestinal microflora; Liver; Median (statistics); Metabolites; Metastases; Metastasis; Microbiomes; Microbiota; Molecular chains; Non-small cell lung carcinoma; Patients; Pharmacodynamics; Pharmacology; Prostate; Quality assessment; Quality of life; Reactive oxygen species; Sarcoma; Secondary metabolites; Side effects; Solid tumors; Statistical analysis; Statistical methods; Survival; Therapy; Tumors
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/S0959-8049(16)33049-0

Dysbiosis impacts in the natural history of cancer. A set of experimental data sustains the potential of how manipulations of the gut microbiota might improve the outcomes of cancer patients and can amplify the activity of pleiotropic agents, through selective induction of Reactive Oxygen Species in cancer cells. Robust experimental demonstrates that commensal bacteria promotes antitumor immunity and synergizes with PD-Li and CTLA4 disrupting agents. Serum samples from consenting cancer patients (n = 92) and healthy individuals (n = 94) have been analyzed in an immune-precipitation assay, panel of 30 strains of commensal bacteria. This technology platform permits the identification of a dysbiotic profile in serum of cancer patients vs healthy subjects. A galenic process has been developed to lead to a postbiotic extract, lGlBO6t, that contains secondary metabolites from commensal bacteria present in serum of cancer patients. A clinical plan, randomized double blind, is under implementation in solid tumors in combination with pleiotropic agents or with PD-i/CTLA4 interacting agents. Early data from an compassionate program with 1G1806 is given to advanced cancer patients in combination, as single agent or as maintenance therapy is available. 35 non selected consecutive patients with advanced solid tumors are the subject of this analysis. 1G0608 is given orally, 600mg total dose daily, on a continuous basis. The median ECOG PS at entry = 2(1-3), ninety-four % of the patients being Stage IV, 29% with liver mestastasis, equal number with bone metastasis. 30 cases have received 1G1806 for >2 years. Most common side effects are dysgeusia and mild gastric discomfort. The program included a planned assessment of patient's quality of life (QoL) by using the EORTC QLC-C30 questionnaire at baseline and every other month (mo). An intrapatient baseline vs 2 mo QLC-30 information shows significant improvement in 12/35 patients, moreover the improvement pattern noted at 2 mo is confirmed at the 4 mo time point. The serum dysbiotic profile detectable at baseline becomes negative in most of the patients during 1G1806 therapy. The median survival f, Kaplan-Meler is 25 mo (95% CL 17-): the survival rates at 12, 24 and 36 mo are 82% (69-95), 57% (35-69) and 37% (17.5-56) respectively. An intrapatient analysis shows that statistical deviations, long lasting tumor control and improved survival, not justified by indolent disease or the play of chance has been attained in 9 cases