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.

Renal Transplant Immunosuppression Impairs Natural Killer Cell Function In Vitro and In Vivo

“…Alemtuzumab is a known T cell, B cell and dendritic cell depleting antibody [37], [38]. Alemtuzumab has been previously reported to spare NK cells [39], marginally decrease CD16 + NK cell counts until 1–2 months after treatment [40], [41], or to deeply suppress NK cells for over 9 months after treatment [42]. Our results demonstrate that compared to other lymphocytes, NK cells are relatively spared by alemtuzumab.…”

Human Peripheral Blood Mononuclear Cells Exhibit Heterogeneous CD52 Expression Levels and Show Differential Sensitivity to Alemtuzumab Mediated Cytolysis

“…Alemtuzumab has been approved for the treatment of patients with advanced chronic lymphocytic leukemia (CLL) [6], [7], [8]. This antibody has also been utilized in the treatment of a wide range of diseases including rheumatoid arthritis [9], [10], [11], non-Hodgkin’s lymphoma [12], [13] and T- cell lymphoma [14], [15]. In recent phase 2 (CAMMS223) clinical studies, alemtuzumab showed efficacy in the treatment of relapsing-remitting multiple sclerosis [16].…”

Expansion of a Clonal CD8+CD57+ Large Granular Lymphocyte Population After Autologous Stem Cell Transplant in Multiple Myeloma

“…18,19 Clonal T cells also have been identified in other B-cell malignancies. 20,21 In our study, we have defined a distinct cytotoxic CD8+CD57+ clonal T-cell expansion in the bone marrow occurring in the setting following autologous transplant. The phenotype of this population is strikingly similar to the population described in the peripheral blood of MGUS and myeloma patients.…”