Clonal CD8+ and CD52– T cells are induced in responding B cell lymphoma patients treated with Campath-1H* (anti-CD52)

Abstract: Five patients with non-Hodgkin's lymphoma (NHL) and 4 patients with chronic lymphocytic leukaemia (CLL) were treated with the CDR-grafted (rat × human) monoclonal antibody (mAb) Campath-1H (anti-CD52). Tumour regression was noted preferentially in peripheral blood and in the bone marrow but lymph nodes were less affected. Normal blood B and T cells were profoundly reduced in all patients whereas CD16⁺ NK cells and CD14⁺ monocytes decreased marginally. In all responding CLL patients CD52-negative T but not B cells appeared during treatment and persisted for several months (4–19+) during unmaintained follow-up. Clonal T cells defined as a predominance of a single T cell receptor (TCR) V gene usage, in one case verified by TCR CDR3 fragment analysis and nucleotide sequencing, emerged within the CD52^–/CD8⁺ cell population during Campath-1H therapy in 2 CLL patients, both achieving a long-lasting remission. The increase in CD8⁺ T cell expansions (up to 23-fold) during unmaintained remission and follow-up suggest that the clonal CD8⁺ cells may represent regulatory T cells controlling the growth of the tumour B cell clone. Clonal T cells might thus be a target for an immune therapeutic intervention in B cell tumours.