A systematic approach to biomarker discovery; Preamble to "the iSBTc-FDA taskforce on immunotherapy biomarkers"

Department of Medicine, Division of Hematology Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, 15213, USA.
Journal of Translational Medicine (Impact Factor: 3.99). 01/2009; 6:81. DOI: 10.1186/1479-5876-6-81
Source: PubMed

ABSTRACT The International Society for the Biological Therapy of Cancer (iSBTc) has initiated in collaboration with the United States Food and Drug Administration (FDA) a programmatic look at innovative avenues for the identification of relevant parameters to assist clinical and basic scientists who study the natural course of host/tumor interactions or their response to immune manipulation. The task force has two primary goals: 1) identify best practices of standardized and validated immune monitoring procedures and assays to promote inter-trial comparisons and 2) develop strategies for the identification of novel biomarkers that may enhance our understating of principles governing human cancer immune biology and, consequently, implement their clinical application. Two working groups were created that will report the developed best practices at an NCI/FDA/iSBTc sponsored workshop tied to the annual meeting of the iSBTc to be held in Washington DC in the Fall of 2009. This foreword provides an overview of the task force and invites feedback from readers that might be incorporated in the discussions and in the final document.

Download full-text


Available from: Sylvia Janetzki, Aug 21, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Assay miniaturization and the implementation of high-density 1,536-microwell screening increase the speed and efficiency of screening and lead discovery. To serve this need, a platform of miniaturizable assay technologies has been assembled for specific biological targets. This platform will enable initiation and completion of uHTS screens in a straightforward and expeditious manner. Although faster primary screening does contribute to a reduction in timelines, the process of assay development can become a bottleneck. Assay technologies that do not require the use of target-specific reagents can reduce the time necessary for assay development. Assays that measure inhibition of tyrosine kinases can be configured in a competitive format where only the enzyme itself is specific to the assay. In this context, several technologies, including time-resolved fluorometry (also known as DELFIA), time-resolved fluorescence resonance energy transfer (also known as LANCE( trade mark )), fluorescence polarization, enzyme fragmentation complementation assay, and confocal laser scanning imaging, were examined. Quality parameters such as assay reproducibility, signal:background ratio, Z factor, and assay sensitivity were compared. Additionally, the relative merits of each of these technologies are assessed in terms of assay miniaturization, ease of development, ultimate screening capability, efficiency, and cost.
    Assay and Drug Development Technologies 05/2004; 2(2):141-51. DOI:10.1089/154065804323056486 · 2.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although tumor-infiltrating T cells have been documented in ovarian carcinoma, a clear association with clinical outcome has not been established. We performed immunohistochemical analysis of 186 frozen specimens from advanced-stage ovarian carcinomas to assess the distribution of tumor-infiltrating T cells and conducted outcome analyses. Molecular analyses were performed in some tumors by real-time polymerase chain reaction. CD3+ tumor-infiltrating T cells were detected within tumor-cell islets (intratumoral T cells) in 102 of the 186 tumors (54.8 percent); they were undetectable in 72 tumors (38.7 percent); the remaining 12 tumors (6.5 percent) could not be evaluated. There were significant differences in the distributions of progression-free survival and overall survival according to the presence or absence of intratumoral T cells (P<0.001 for both comparisons). The five-year overall survival rate was 38.0 percent among patients whose tumors contained T cells and 4.5 percent among patients whose tumors contained no T cells in islets. Significant differences in the distributions of progression-free survival and overall survival according to the presence or absence of intratumoral T cells (P<0.001 for both comparisons) were also seen among 74 patients with a complete clinical response after debulking and platinum-based chemotherapy: the five-year overall survival rate was 73.9 percent among patients whose tumors contained T cells and 11.9 percent among patients whose tumors contained no T cells in islets. The presence of intratumoral T cells independently correlated with delayed recurrence or delayed death in multivariate analysis and was associated with increased expression of interferon-gamma, interleukin-2, and lymphocyte-attracting chemokines within the tumor. The absence of intratumoral T cells was associated with increased levels of vascular endothelial growth factor. The presence of intratumoral T cells correlates with improved clinical outcome in advanced ovarian carcinoma.
    New England Journal of Medicine 01/2003; 348(3):203-13. DOI:10.1056/NEJMoa020177 · 54.42 Impact Factor
  • Journal of Clinical Oncology 03/2003; 21(4):586-7. DOI:10.1200/JCO.2003.12.065 · 18.43 Impact Factor
Show more