Gamma irradiated human platelet lysate as a serum substitute for ex vivo expansion of immune cells

Abstract

Background & Aim Adoptive immunotherapy is emerged as one of the leading treatments in cancer. The clinical applications require ex vivo expansion of lymphocytes to therapeutic doses in a timely manner under strict cGMP compliance. Culture medium is one important determinant for successful cell expansion. Many efficient expansion strategies incorporate serum or plasma as a supplement to provide cells with a richer milieu to grow in. However, autologous serum has supply limitations for meeting the expected commercial demand for immunotherapies. Moreover, pooled human serum or animal-derived serum bring the inherent concern about risk of infection transmission. Human platelet lysate (hPL) is well recognized as an efficient xenogenic-free alternative to FBS for manufacturing cells and cellular products. To address the risk management for pathogen transmission, we have assessed the feasibility of gamma irradiation as a pathogen reduction treatment for hPL and validated its efficacy for virus inactivation. Our gamma irradiation process demonstrated low impact on hPL potency and long-term stability. In this study, we evaluated the potential use of gamma-irradiated human platelet lysate (GI hPL) on immune cell expansion. Methods, Results & Conclusion To compare the potency of different culture supplements, peripheral blood mononuclear cells were activated and expanded in the presence of interleukin 2 (IL2). T cell expansion in GI hPL supplemented medium showed higher yields than the expansion obtained with autologous plasma. For NK cell expansion, the potency of GI hPL and plasma were comparable. The cytotoxicity of NK cells against K562 cells was high and comparable for both GI hPL and plasma. High viability was observed in all expanded lymphocytes. The results suggest that GI hPL is a viable and valuable alternative cell culture supplement for ex vivo expansion of immune cells.