Optimized process for regulatory T cell activation and expansion using Dynabeads™ Treg CD3/CD28 for clinical applications

CD4+CD25+ Tregs are a suppressive subset of CD4+ T helper cells important for the regulation of immune responses. Tregs are proven highly effective in preventing graft versus host disease (GVHD) and autoimmunity in murine models. The relative frequency of Tregs in peripheral blood is approximately 1-2% of total lymphocytes implicating the necessity of ex vivo expansion of Tregs prior to adoptive transfer for most clinical applications. The Dynabeads™ CD3⁄CD28 CTS™ has been developed for ex vivo isolation, activation, and expansion of human T cells for use in various immunotherapies. To address the specific needs for Treg expansion, we have generated a new product, Dynabeads™ Treg CD3/CD28, designed to provide optimal activation and expansion of Tregs. We have compared the functionality of Dynabeads™TregCD3/CD28 with other existing technologies (competitors and Dynabeads™ CD3⁄CD28 CTS™) regarding expansion of CD4+CD25+CD127low flow sorted Tregs and magnetically isolated Tregs. Our studies demonstrate superior fold expansion of functional Tregs with the Dynabeads™ Treg CD3/CD28. We show several hundred fold expansion of Treg cells in 14 days culture and with maintenance of high FOXP3 expression and suppressive activity. This optimized Dynabeads™ Treg CD3/CD28 support consistent and scalable Treg manufacturing for immunotherapies, supplementing our Cell Therapy System (CTSTM) portfolio. For Research Use Only. Not for use in diagnostic procedures

CAR T Cell Therapy: A Game Changer in Cancer Treatment

The development of novel targeted therapies with acceptable safety profiles is critical to successful cancer outcomes with better survival rates. Immunotherapy offers promising opportunities with the potential to induce sustained remissions in patients with refractory disease. Recent dramatic clinical responses in trials with gene modified T cells expressing chimeric antigen receptors (CARs) in B-cell malignancies have generated great enthusiasm. This therapy might pave the way for a potential paradigm shift in the way we treat refractory or relapsed cancers. CARs are genetically engineered receptors that combine the specific binding domains from a tumor targeting antibody with T cell signaling domains to allow specifically targeted antibody redirected T cell activation. Despite current successes in hematological cancers, we are only in the beginning of exploring the powerful potential of CAR redirected T cells in the control and elimination of resistant, metastatic, or recurrent nonhematological cancers. This review discusses the application of the CAR T cell therapy, its challenges, and strategies for successful clinical and commercial translation

Ex vivo expansion of human T cells for adoptive immunotherapy using the novel Xeno-free CTS Immune Cell Serum Replacement

The manufacture of clinical grade cellular products for adoptive immunotherapy requires ex vivo culture and expansion of human T cells. One of the key components in manufacturing of T cell therapies is human serum (HS) or fetal bovine serum (FBS), which can potentially expose immunotherapy recipient to adventitious infectious pathogens and are thus considered as non-cGMP compliant for adoptive therapy. Here we describe a novel xeno-free serum replacement (SR) with defined components that can be reproducibly used for the production of clinical grade T-cell therapies in combination with several different cell culture media. Dynabeads CD3/CD28 Cell Therapy System (CTS)-activated or antigen-specific T cells expanded using the xeno-free SR, CTS Immune Cell SR, showed comparable growth kinetics observed with cell culture media supplemented with HS or FBS. Importantly the xeno-free SR supplemented medium supported the optimal expansion of T cells specific for subdominant tumour-associated antigens and promoted expansion of T cells with central memory T-cell phenotype, which is favourable for in vivo survival and persistence following adoptive transfer. Furthermore, T cells expanded using xeno-free SR medium were highly amenable to lentivirus-mediated gene transduction for potential application for gene-modified T cells. Taken together, the CTS Immune Cell SR provides a novel platform strategy for the manufacture of clinical grade adoptive cellular therapies