And knowledge about the treatment impact, response and biomarker profile is
And knowledge about the treatment impact, response and biomarker profile is generated (see for example [1]). Two conceptually related proposals for clinical trial design, the adaptive [2,3] and two-stage [4] clinical trial design paradigms, have been recently proposed to overcome at least some of the limitations associated with the traditional clinical development path for new therapeutics. Both the adaptive and two-stage clinical design paradigms are integrally dependent on the development and application of robust, relevant and statistically-based biomarker studies to guide the clinical development process; accordingly, increased implementation of these approaches has fostered a renewed emphasis on the development of high quality biomarker research [5-9]. Recent focus on the establishment and implementation of integrated translational research programs has highlighted a critical role for biomarkers during preclinical stages of research. In addition to guiding go-no-go decisions to move new agents into the clinic, preclinical biomarker studies commonly evaluate mechanistic aspects of the product, and often serve to define both the biomarkers to be studied and the assays to be?2011 Kalos; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Kalos Journal of Translational Medicine 2011, 9:138 http://www.translational-medicine.com/content/9/1/Page 2 ofemployed in the clinical trial. A strong argument can thus be made for the close integration of biomarker development from the preclinical through the clinical trial process.T cell therapy clinical trialsThe concept of enhancing cellular immunity through the transfer of ex-vivo expanded T cells was pioneered by Greenberg et al., who coined the term PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28878015 FruquintinibMedChemExpress HMPL-013 adoptive T cell transfer to describe the process [10]. The first clinical application of adoptive T cell transfer involved reconstitution of cellular anti-CMV immunity in the context of allogeneic bone marrow transplantation [11]; since then, adoptive T cell transfer has been evaluated as a treatment modality against a number of viral diseases [12-14]. Significant effort has been put forth over the past few years to evaluate the potential to treat cancer via the adoptive transfer of T lymphocytes, both effector lymphocytes (CD8 and CD4) and regulatory (Treg) cells, manipulated ex-vivo to generate large numbers and in some cases to enhance their activity (see for examples [15-17]). Such efforts been enabled by enhanced understanding of T cell immunobiology, and facilitated by the development of approaches to expand and manipulate T cells ex vivo [18-20], methodologies to enable manufacture under Good Manufacturing Practice (GMP) [21-23], as well as genetic approaches to augment T cell specificity and function [24,25]. These developments have facilitated a broad range of clinical trials to evaluate the ability of T cell therapy-based strategies to target tumors. T cells, derived from the periphery [17,26-28], from tumor infiltrating lymphocytes (TIL) [29-31], or have been enriched for virus-specificities [13,32,33] to enhance persistence have been infused into patients after ex-vivo expansion either as bulk or antigen-specific populations. More recently, advances in the practical ability to genetically en.
