Ingrid Eriksson

Idiotype‐specific T lymphocytes in monoclonal gammopathies: evidence for the presence of CD4+ and CD8+ subsets

Tumour‐specific CD4+ T helper (Th) and CD8+ T cytotoxic (Tc) cells may participate in the control and eradication of tumour cells. In the present study, idiotype‐specific stimulation of CD4+ and CD8+ blood T cells from patients with monoclonal gammopathy of undetermined significance and patients with untreated multiple myeloma stage I was examined. Activation was measured in the CD4+ and CD8+ subsets enriched by magnetic microbeads as the incorporation of 3H‐thymidine and the secretion of interferon (IFN)‐γ, interleukin (IL)‐2 and IL‐4 by single cells using the enzyme‐linked immunospot assay. Idiotype‐specific T cells were found in four of seven patients. Stimulation was mainly confined to the CD4+ subset in three of the four responding patients. This type of response was major histocompatibility complex (MHC) class II restricted as it could be inhibited by monoclonal antibodies against MHC class II (HLA‐DR), but not against class I (HLA‐ABC) molecules. Idiotype‐specific CD8+ T cells were also demonstrated in these patients although at a lower frequency. One patient showed a strong and dominating activation of CD8+ T cells which could be blocked by antibodies against HLA‐ABC but not against HLA‐DR. Idiotype‐specific CD4+ or CD8+ T cells were mainly of the type‐1 subsets as judged by their secretion of IFN‐γ and IL‐2. Thus, this study provides evidence for the presence of idiotype‐specific and MHC‐restricted CD4+ and CD8+ T cells of the type‐1 subsets in patients with monoclonal gammopathies. Such T cells with the potential to control the growth of tumour B cells may be a suitable target for immunotherapeutic interventions in patients.

Long-term effects of idiotype vaccination on the specific T-cell response in peripheral blood and bone marrow of multiple myeloma patients.

Objectives:  To elucidate long‐term effects of idiotype (Id) vaccination on Id‐specific T cells of multiple myeloma (MM) patients and compare Id‐specific T‐cell responses of peripheral blood with those of bone marrow (BM).

Lenalidomide as immune adjuvant to a dendritic cell vaccine in chronic lymphocytic leukemia patients

We previously showed that immunization with ex vivo‐ generated autologous dendritic cells loaded with apoptotic tumor cells (Apo‐DC) potentiated tumor‐specific immunity in chronic lymphocytic leukemia (CLL) patients. Here, we evaluated safety and immunogenicity of Apo‐DC in combination with lenalidomide, granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), and low‐dose cyclophosphamide (CTX).