A phase I trial of autologous cytokine-induced killer cells for the treatment of relapsed Hodgkin disease and non-Hodgkin lymphoma

Abstract

We have previously reported on the ex vivo generation of cytotoxic effector cells, termed cytokine-induced killer (CIK) cells, that have both in vitro and in vivo antitumor activity in murine models. We now report on our efforts for the large-scale expansion of CIK cells and also present preliminary results from a phase I clinical trial. Nine patients with advanced Hodgkin disease (n = 7) and non-Hodgkin lymphoma (n = 2), all of whom had relapsed after an autologous transplantation, were treated with escalating doses of CIK cells (3 patients at each dose level of 1 x 10(9) , 5 x 10(9) , or 1 x 10(10) cells). The CIK cells were produced by culturing unselected cells from steady-state apheresis products with interferon gamma, OKT3, and interleukin 2. After 21 days in culture, with the addition of fresh media and interleukin 2 every 3 to 4 days, the median culture was 97% viable (range, 61%-100%), 98% CD3 + (range, 66%-99%), 76% CD8 + (range, 27%-96%), 23% CD4 + (range, 6%-78%), 20% CD3 + CD56 + (range, 8%-58%), and <1% CD16 + 56 + (range, 0.2%-7.7%). The CD3 + CD56 + cells have previously been shown to exhibit the most cytotoxic activity. The absolute number of CD3 + CD56 + cells typically expanded 290-fold (range, 3- to 4000-fold) under these culture conditions. In vitro cytotoxic activity was measured against a human B-cell tumor line (OCI-Ly8). At a 40:1 effector-target cell ratio, CIK cells killed 32% (range, 2%-69%) of the target cells. A total of 21 infusions were administered to 9 patients. The number of CIK cells infused ranged from 1.0 x 10(9) to 1.0 x 10(10) per treatment. Toxicity was minimal, and there were no immediate adverse reactions to the infusions. Two patients had partial responses, and 2 patients had stabilization of disease: 1 for more than 18 months. Considering that these were heavily pretreated patients with advanced hematologic malignancies, we believe that CIK cells expanded in this fashion may have utility for the treatment of high-risk patients with evidence of minimal residual disease after autologous transplantation.

Cytotoxic effect of trans-cinnamaldehyde on human leukemia K562 cells

“…They are generated from peripheral blood lymphocytes and represent a rare subset of circulating lymphocytes (from 1% to 5% of peripheral blood lymphocytes) [17] . At maturity, CIK cells exhibit potent cytotoxicity against autologous acute myeloid leukemia (AML) targets, as well as against allogeneic myeloid leukemia cells, regardless of the HLA types of these targets.…”

Silencing Human NKG2D, DAP10, and DAP12 Reduces Cytotoxicity of Activated CD8+ T Cells and NK Cells

“…These T cells have broad in vitro and in vivo biological activity against inoculated tumors after both syngeneic and allogeneic bone marrow transplantation in rodent models (29,30). Autologous infusion of cells of this type in patients has been associated with minimal toxicity, can reduce the risk of tumor recurrence in patients with hepatocellular carcinoma after surgical resection, and may induce partial remissions in patients with relapse of lymphoma after bone marrow transplantation (31,32). In this study, we extended our evaluation of the signaling requirements for induction of cytotoxicity by activated and expanded human CD8 ϩ T cells.…”

Effect of Chinese Medicine XIAOJI Decoction Combined with Platinum-Based Chemotherapy and Transfusion of Cytokine-Induced Killer Cells in Patients with Stage III B/IV Non-Small Cell Lung Cancer

“…At the present, the approaches to treat lung cancer are abundant constantly. Adjuvant chemotherapy and targeted However, immunotherapy has become one of promising strategies for the treatment of certain malignant tumors in recent decades [18], Tumors may release some materials that suppressed the immune system; the immunosuppressive response may be more servers after adjuvant chemotherapy. Thus, the tumors through some mechanisms to evade destruction by the immune system could be an important reason leading poor outcome in advanced lung cancer.…”