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

Abstract

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.

Toward precision manufacturing of immunogene T-cell therapies

“…Thus, HS substitutes of nonanimal origin may be alternatives in the setting of cell manufacturing and are currently being explored. In this regard, recent studies showed that an immune cell serum replacement (ThermoFisher Scientific) promotes at least equivalently efficient T-cell proliferation as compared with conventional expansion media containing HS [97,114]. It is expected that serum substitution will be integrated into current T-cell manufacturing for economical purposes with the goal of maintaining or improving the quality of T-cell products.…”

Methods to manufacture regulatory T cells for cell therapy

“…Serum provides critical factors for T reg growth but is costly, and can add significant regulatory hurdles due to its variability and the risk of possible adverse events . The use of serum‐free media, such as OpTmizer (ThermoFisher), ImmunoCult‐XF (Stemcell Technologies) or serum replacement supplements, would alleviate these concerns .…”

T Cell Receptor Engineered Lymphocytes for Cancer Therapy

“…Human serum is expensive and requires extensive testing before use in manufacturing cGMPcompliant T cell therapies. To circumvent the use of human serum, it is possible to use CTS TM OpTmizer TM supplemented with serum free CTS TM Immune Cell SR, which shows similar kinetics, expansion, and transduction efficiency after 2 weeks of T cell culture (Smith et al, 2015).…”