Use of human leukocyte antigen-mismatched allogeneic lymphokine-activated killer cells and interleukin-2 in the adoptive immunotherapy of patients with malignancies

Abstract

Clinical effects and side effects were studied in the adoptive immunotherapy of patients bearing malignant diseases using human leukocyte antigen (HLA)-mismatched allogeneic lymphokine-activated killer (LAK) cells. Allogeneic LAK cells were induced from peripheral blood lymphocytes (PBL) of normal donors by means of initial stimulation with pokeweed mitogen (PWM). Six of 15 patients applied in the adoptive immunotherapy showed clinical effects such as partial or complete regression of pulmonary metastasis, pleural effusion and primary tumor. All pulmonary metastatic lesions were eliminated in one case by this adoptive immunotherapy combined with chemotherapy. Generally toxic effects were chillness, fever and general fatigue which were reversible, and no allergic side effects occurred even though allogeneic LAK cells were injected frequently except one patient who showed preshock like symptom accompanied with leukocytopenia and continuous hypotension immediately after infusion but was finally rescued. In the patients who received more than 10(11) of allogeneic LAK cells, anti-HLA class I antibodies appeared without any evidence of autoantibody. However, immunological side effects were never experienced after injection of allogeneic LAK cells even when the anti-HLA class I antibodies appeared in the patients. Taken together, allogeneic LAK cells could be considered as alternative therapy for patients with malignancies who could not supply sufficient materials of autologous LAK cells.

Clinical scale isolation of T cell-depleted CD56+ donor lymphocytes in children

“…[13][14][15] It has been shown in the mouse model, that adoptive transfer of donor NK cells can induce antileukemic effects without inducing GVHD 16 and prevention of GVHD has even been reported. 17 However, there remain little data regarding infusion of allogeneic NK cells in relapsed patients after transplantation 18,19 and, to our knowledge, treatment of minimal residual disease has not been evaluated at all. …”

In vivo tracking of genetically engineered, anti-HER2/neu directed natural killer cells to HER2/neu positive mammary tumors with magnetic resonance imaging

“…Various investigators evaluated the antitumoral activity of NK cells, including the mechanisms of immunosurveillance, escape strategies of the malignant cells and risk of adverse reactions (1)(2)(3). Cancer therapy with NK cells can be performed by two approaches: Either by activation of endogenous NK cells through systemic application of cytokines (4,5) or by adoptive transfer of ex vivo-expanded and activated autologous or donor derived NK cells (6)(7)(8). The latter approach includes the use of cytotoxic NK cell lines that are suitable for clinical use (9).…”

Intracardiac echocardiography off piste? Closure of the left atrial appendage using ICE and local anesthesia

“…Approaches to inhibit tumor proliferation by improving NK cell defense comprise activation of endogenous NK cell reserves by stimulation via cytokines (32) or by ex vivo expansion (33). Unfortunately, while these therapeutic approaches are well tolerated by patients (34), only few have reaped significant anticancer benefit (31).…”