Tabelecleucel

Tabelecleucel is an allogeneic, EBV-specific T-cell immunotherapy which targets and eliminates EBV-infected cells in an HLA-restricted manner. Tabelecleucel has an equivalent mechanism of action to that demonstrated by endogenous circulating T cells in the donors from which the medicinal product is derived. The T-cell receptor of each clonal population within tabelecleucel recognises an EBV peptide in complex with a specific HLA molecule on the surface of target cells (the restricting HLA allele) and allows the medicinal product to exert cytotoxic activity against the EBV-infected cells.

Pharmacodynamic effects

Across multiple clinical studies, systemic cytokine levels of IL-1β, IL-2, IL-6 and TNFα did not meaningfully change from baseline after administration of tabelecleucel.

Upon administration of tabelecleucel, circulating EBV-targeting cytotoxic T lymphocytes show a 1.33-median fold increase from baseline to peak expansion. Responders demonstrate a 1.74-median fold increase whereas non-responders show a 0.67-median fold decrease. The specific timing of this expansion varies widely among patients; however, peak expansion has been shown to correlate with response to tabelecleucel.

Tabelecleucel is an ex vivo expanded T-cell product that is not genetically modified. Hence, the nature and the intended use of the product are such that conventional studies including absorption, distribution, metabolism and excretion are not applicable.

Special populations

Renal and hepatic impairment

The safety and efficacy of tabelecleucel have not been studied in patients with severe renal or hepatic impairment. However, the influence of renal or hepatic impairment on the pharmacokinetics of tabelecleucel is considered to be very unlikely.

Tabelecleucel is comprised of human T cells that are not genetically modified; therefore, in vitro assays and studies in ex vivo models or in vivo models cannot accurately assess and predict the toxicological characteristics of this product in humans. Hence, conventional toxicology, carcinogenicity, genotoxicity, mutagenicity and reproductive toxicology studies have not been performed with tabelecleucel.

Studies conducted in immunodeficient animal models for EBV+ PTLD revealed no overt signs of toxicity (e.g. loss of activity or weight loss) associated with a single dose of tabelecleucel.