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Evaluation of safty of personalized Colon Cancer Cell Vaccine

ABSTRACT: Intervention 1: Intervention group: Patients with colorectal cancer, stage 4 which receive chemotherapy and vaccine. Autologous vaccine will be injected in two periods. The first period consists of three consecutive doses: the first dose will be injected one week after diagnosis /surgery, the next two doses will be injected with a week interval. One week after the third injection, chemotherapy will begin. After the first period, chemotherapy begins and continues for six months. The second period of the vaccine starts one month after chemotherapy and includes three consecutive vaccine doses with a distance of one week. Chemotherapy begins and continues two weeks after the sixth injection. Ten million irradiated tumor cells with 10 million BCG organisms are injected intradermally in the first and second injectons. The third, fourth, fifth and sixth injections contain 10 million irradiated tumor cells. Intervention 2: Control group: Patients with colorectal cancer, stage 4 which receive Chemotherapy treatment 5 weeks after diagnosis /surgery. Primary outcome(s): Investigation of tumor markers levels (CEA, CA19-9) and liver enzymes and no new tumor formation. Timepoint: 6 months after the last vaccination. Method of measurement: Measure the umor markers levels (CEA, CA19-9) and liver enzymes concentration via Elisa method, and assay the new tumor formation via colonoscopy. Study Design: Randomization: Not randomized, Blinding: Not blinded, Placebo: Not used, Assignment: Parallel, Purpose: Treatment.

DISEASE(S): Malignant Neoplasm Of Colon, Malignant Neoplasm Of Rectosigmoid Junction, Malignant Neoplasm Of Rectum, Malignant Neoplasm Of Anus And Anal Canal,C18, C19,Colorectal Cancer

PROVIDER: 2504199 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Intervention 1: Intervention group: Patients with colorectal cancer, stage 4 which receive chemotherapy and vaccine. The allogene vaccine (including three colon cancer cell lines) will be injected in two periods. The first period consists of three consecutive doses: the first dose will be injected one week after diagnosis /surgery, the following two doses will be injected with a week interval. One week after the third injection, chemotherapy will begin. After the first period, chemotherapy begins and continues for six months. The second period of the vaccine starts one month after chemotherapy and includes three consecutive vaccine doses with a distance of one week. Chemotherapy begins and continues two weeks after the sixth injection. 300 million tumor cells (108 cells from each cancer cell line) with 1 million BCG organisms are injected intradermally in the first and second injections. The third, fourth, fifth, and sixth injections contain 300 million irradiated tumor cells. Intervention 2: Control group: Patients with colorectal cancer, stage 4 which receive Chemotherapy treatment 5 weeks after diagnosis /surgery. Primary outcome(s): Measuring the levels of CA19-9. Timepoint: 6 months after the last vaccination. Method of measurement: via Elisa method.;Measuring the levels of CEA. Timepoint: 6 months after the last vaccination. Method of measurement: via Elisa method.;Measuring the levels of alanine aminotransferase. Timepoint: 6 months after the last vaccination. Method of measurement: via Elisa method.;Measuring the levels of aspartate aminotransferase. Timepoint: 6 months after the last vaccination. Method of measurement: via Elisa method.;Measuring the levels of alkaline phosphatase. Timepoint: 6 months after the last vaccination. Method of measurement: via Elisa method.;Measuring the levels of glutamyl tarnspeptidase. Timepoint: 6 months after the last vaccination. Method of measurement: via Elisa method.;Investigation of tumor formation. Timepoint: 6 months after the last vaccination. Method of measurement: via colonoscopy. Study Design: Randomization: Not randomized, Blinding: Not blinded, Placebo: Not used, Assignment: Parallel, Purpose: Treatment.

Project description:Using whole-blood transcriptional profiling, we investigated differences in the host response to vaccination and challenge in a rhesus macaque AIDS vaccine trial. Samples were collected from animals prior to and after vaccination with live irradiated vaccine cells secreting the modified endoplasmic reticulum chaperone gp96-Ig loaded with SIV peptides, either alone or in combination with a SIV-gp120 protein boost. Additional samples were collected following multiple low-dose rectal challenge with SIVmac251. Animals in the boosted group had a 73% reduced risk of infection. Surprisingly, few changes in gene expression were observed during the vaccination phase. Focusing on post-challenge comparisons, in particular for protected animals, we identified a host response signature of protection comprised of strong interferon signaling after the first challenge, which then largely abated after further challenges. We also identified a host response signature, comprised of early macrophage-mediated inflammatory responses, in animals with undetectable viral load five days after the first challenge, but which had unusually high viral titers after subsequent challenges. Statistical analysis showed that prime-boost vaccination significantly lowered the probability of infection in a time-consistent manner throughout several challenges. Given that humoral responses in the prime-boost group were highly significant pre-challenge correlates of protection, the strong innate signaling after the first challenge suggests that interferon signaling enhances vaccine-induced antibody responses and is an important contributor to protection from infection during repeated low-dose exposure to SIV. 36 Indian-origin outbred, young adult, male and female rhesus macaques divided into thre vaccination groups of 12 animals each. Groups were balanced for Mamu-A*01 (three in each group), Mamu-B*08 (one in each group), and for susceptible and resistant TRIM5α alleles. There were no Mamu-B*17+ animals. The prime group (PG) received Gp96 SIV Ig vaccine 292 cells that were transfected with plasmids encoding gp96-Ig, SIVmac251 rev-tat-nef, Gag and gp160 (35). They were injected intraperitoneally with 107 irradiated gp96SIVIg vaccine cells in HBSS, which secrete 10 μg of gp96SIVIg per 24 h. For the prime-boost group (PBG), 100 g of rSIVgp120 protein was added to the vaccine cells. The control group received 292-gp96 Ig cells not transfected with SIV antigens. After a 32-week vaccination phase, which consisted of priming in weeks 0, 6, and 25 and (for the PBG only) additional boosts in weeks 6 and 25, all animals were subject to up to seven weekly low-dose intrarectal challenges starting at 33-week with SIVmac251 at a dosage of 120 TCID50. Whenever an animal had detectable viral load (>50 copies/ml of plasma) at 5 days post challenge, it was considered viremic, further challenges were suspended, and only viral load screening continued on a weekly basis. Whole blood samples (preserved in PAXgene tubes) were collected 2 weeks prior to the first prime, 1 week after the first prime, 2 weeks before and 1 week after the third prime, 1 week before the first challenge, for newly infected animals five days into the corresponding study week and from viremic animals four days into the study week (also denoted as challenge 2 and challenge 3). Total RNA was isolated from Paxgene tubes using Paxgene Blood RNeasy Mini Kits (Qiagen) following the manufacturer’s protocol. RNA quality was assessed on an Agilent 2100 Bioanalyzer using the nanochip format, and only intact RNA was used for microarray analyses.

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Evaluation of safty of personalized Colon Cancer Cell Vaccine

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