Infusing advanced cancer patients with tumour antigen-specific CD4+ and CD8+ T cell clones

Previous attempts to treat human cancer by infusing tumour antigen- specific T cells have highlighted the need to deliver CD4+ T cells to maintain an effective CD8+ T cell response in vivo. We have explored a protocol designed to generate both CD4+ and CD8+ T cell clones for infusing advanced cancer patients. T cells were reactivated in vitro from patients with EBV-associated tumours, melanoma and prostate cancer using DCs pulsed with peptides representing defined epitopes within tumour antigens. Cloning efficiency was significantly improved by pre-selecting specific cells using an interferon capture assay. CD4+ and/or CD8+ T cell clones were successfully generated from 16/27 patients, six of whom were infused with escalating doses of T cells. Treatments were well tolerated, and functional cells were detectable in blood 1-14 days postinfusion, with some cells present for >2 months. T cell clones were heterogeneous both in their ability to recognise tumour lines and in their homing phenotype. This highlights the value of cloning T cell populations which can be screened prior to infusion to select those with sufficient avidity for the target antigen and with the appropriate homing phenotype.