Project description:In this single arm non-randomized phase II trial, 40 patients with recurrent/metastatic EBV-positive nasopharyngeal carcinoma who failed prior chemotherapy received nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks. The best overall objective response rate was 38% with a median progression-free and overall survival of 5.3 and 19.5 months, respectively. This regimen was well-tolerated and treatment-related adverse events requiring discontinuation were low. There was no correlation of response with PD-L1 expression or tumor mutation burden, however patients with low plasma circulating EBV-DNA titre (<7,800 IU/ml) showed a trend to better response and progression-free survival. Deep immunophenotyping of pre- and on-treatment tumor biopsies demonstrated early activation of the adaptive immune response, with T-cell cytotoxicity seen in responders prior to any clinically evident response. Profiling immune-subpopulations also identified a specific PD-1 and CTLA-4 expressing CD8 subpopulation that predicted for response to combined immune checkpoint blockade in nasopharyngeal carcinoma.
Project description:Mice were immunized with either formalin fixed Influenza A/PR/8/34 (Killed PR8), the 2006-2007 seasonal influenza vaccine, the 2007-2008 seasonal influenza vaccine, a sublethal infection (live PR8) or mock immunized (PBS). Array data was used to distinguish the immunogens from each other and predict which of the three inactivated vaccines would be protective against A/PR/8/34 challenge. two replicates of each peptide was printed on 1 CIM_10kv3 peptide microarray. One microarray were tested for each sample. Image was qualified using in-house metrics for quality assurance.
Project description:Relevant clinical data for POPLAR including treatment arm, histology, overall survival, progression-free survival, and best confirmed overall response.
Project description:Relevant clinical data for OAK including treatment arm, histology, overall survival, progression-free survival, and best confirmed overall response.
Project description:MITO16/MaNGO-OV2 (NCT01706120) is a multicenter, phase IV, single arm trial for advanced stage IIIB-IV or recurrent, previously untreated, ovarian cancer patients receiving carboplatin, paclitaxel plus bevacizumab for six 3-weekly cycles followed by bevacizumab single agent until progression or unacceptable toxicity up to a maximum of 22 total cycles. The trial that was specifically designed with a translational primary endpoint to explore if selected clinical and biological factors could identify ovarian cancer patients with better prognosis in terms of progression free survival and overall survival after combined first-line treatment with chemotherapy plus Bevacizumab. The translational study, designed together with the clinical trial, the translational study implicated the collection of patients’ tissue (formalin-fixed paraffin-embedded – FFPE) and blood samples. Gene expression profile was among the molecular analyses proposed on FFPE samples.
Project description:Interventions: Subctaneus injection of cancer peptide vaccine(three peptides)
Primary outcome(s): Safety Overall survival
Study Design: Single arm Non-randomized
Project description:Interventions: peptide vaccine therapy
Primary outcome(s): We confirm the safety of the peptide vaccine against gastric and colorectal cancer patient.
Study Design: Single arm Non-randomized
Project description:Interventions: Peptide vaccine therapy
Primary outcome(s): We confirm the safety of the peptide vaccine against colorectal cancer patient.
Study Design: Single arm Non-randomized
Project description:A single arm, Phase II trial of carboplatin, nab-paclitaxel, and pembrolizumab (CNP) in metastatic triple negative breast cancer (mTNBC) was designed to evaluate overall response rate (ORR), progression-free survival (PFS), duration of response (DOR), safety/tolerability, and identify pathologic and transcriptomic correlates of response to therapy.
Project description:Immunotherapy provides an alternative approach for cancer treatment. However, in-depth analyses of the effects of immunotherapy on the tumor microenvironment (TME) have not been conducted in non-melanoma tumors. Here we describe changes in the pancreatic ductal adenocarcinoma (PDAC) TME following immunotherapy treatment, and show for the first time that vaccine-based immunotherapy directly alters the TME, inducing neogenesis of tertiary lymphoid structures that convert immunologically quiescent tumors into immunologically active tumors. Alterations in five pathways important for immune modulation and lymphoid structure development (TH17/Treg, NFkB, Ubiquitin-proteasome, Chemokines/chemokine receptors, and Integrins/adhesion molecules) in vaccine-induced intratumoral lymphoid aggregates were associated with improved post-vaccination responses. Additional studies in other cancers and patients treated with other forms of immunotherapy are warranted to further develop signatures defined in intratumoral lymphoid structures into biomarkers that predict effective anti-tumor immune responses. These signatures may also expose therapeutic targets for promoting more robust antitumor immune responses in the TME. Between July 2008 and September 2012, 59 patients were enrolled into an ongoing study of an irradiated, allogeneic GM-CSF-secreting pancreatic tumor vaccine (GVAX) administered intradermally either alone or in combination with immune modulatory doses of cyclophophamide (Cy) as neoadjuvant and adjuvant treatment for patients with resectable pancreatic ductal adenocarcinoma (PDAC). Patients were randomized 1:1:1 to 3 treatment arms. In Arm A, patients received GVAX alone; in Arm B, patients received GVAX plus a single intravenous dose of Cy at 200 mg/m2 1 day prior to each vaccination; in Arm C, patients received GVAX plus oral Cy at 100 mg once daily for 1 week on and 1 week off. Up to 6 GVAX treatments were administered and all of the patients remained in their initial treatment arms throughout the duration of the study. All 59 of the patients received the 1st GVAX treatment 2 weeks +/-4 days prior to surgery. Formalin-fixed paraffin-embedded (FFPE) tissue blocks of surgically resected PDAC were obtained from the pathology archive. FFPE tissue blocks from each subject were stained by H&E immediately before the vaccine therapy-induced lymphoid aggregates were microdissected . To better understand the functional status of these vaccine therapy induced lymphoid aggregate structures, gene microarray analysis on RNA isolated from microdissected lymphoid aggregates was performed. Gene expression was compared among samples grouped according to patient overall survival, post-vaccination induction of enhanced mesothelin-specific T cell responses in peripheral blood lymphocytes (PBL), and the intratumoral CD8+ T effector to FoxP3+ Treg ratio. Post-vaccination induction of enhanced mesothelin-specific T cell responses has been reported to correlate with longer survival in patients treated with Panc GVAX.