Briggs, D

Goodyear, O

Green, A M

Lee, S P

Machado, Lee

Marsden, J

McDonald, D

Patel, P

Steven, Neil

Thomas, Wendy

English

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 &gt;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

University of Northampton's Research Explorer

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

Kontos, Christopher D.

College of William & Mary: W&M Publish