Immune response, clinical outcome and safety of dendritic cell vaccine in combination with cytokine-induced killer cell therapy in cancer patients

Abstract

The aim of the present study was to determine the clinical value of autologous immunocyte therapy as a standard treatment regimen for patients with cancer. A total of 121 patients with cancer were included in this study. Subsequent to performing leukapheresis using the Fresenius Kabi System, 1×107 dendritic cells (DCs) for the vaccine and 1×109 cytokine-induced killer (CIK) cells for injection were prepared. An analysis of the immune phenotypes of HLA2DR, CD80 and CD83 for the DCs and of CD3, CD8 and CD56 for the CIK cells, as well as negative detection of bacteria and endotoxin, were used as the quality standards. The delayed-type hyper-sensitivity (DTH) skin test was used to measure the immune response, while physical strength, appetite and sleeping status were analyzed for the clinical outcome. Fever, insomnia, anorexia, joint soreness and skin rashes were recorded as side-effects. Patients received the DC vaccination once a week for six weeks and a CIK cell injection six times within four days. In total, 121 cancer patients with primary tumors located in the colorectum (43.0%), lung (15.7%), breast (11.6%), kidney (5.8%), stomach (4.1%) and other regions (19.8%) were included in the study. A positive cell-mediated cytotoxicity response rate of 76.9% was detected by the DTH skin tests. Improvements in physical strength, appetite and sleeping status were observed in 94.1, 83.9 and 76.3% of cases, respectively. None of the serious adverse side-effects that commonly occur during chemotherapy and radiotherapy were observed. During therapy, 69 cases developed a fever that was resolved with antipyretics, dexamethasone or physical cooling, while 28 cases developed insomnia combined with excitement, 19 cases complained of anorexia, 11 cases complained of joint soreness, which was alleviated using analgesics, and 8 cases developed skin rashes. The combined use of CIK cells with a DC-based cancer vaccination strategy may be used to target innate and adaptive immune mechanisms and synergistically promote positive clinical outcomes. The therapy was safe and no serious adverse side-effects similar to those caused by chemotherapy and radiotherapy were observed. The regimen may have a beneficial effect in the future treatment of patients with cancer.

Clinical value of Pro‑GRP and T lymphocyte subpopulation for the assessment of immune functions of lung cancer patients after DC‑CIK biological therapy

“…A previous study proved that Pro-GRP is highly expressed in SCLC (10), and the specificity and sensitivity of Pro-GRP detection for SCLC diagnosis are higher than those of NSE (22,23). In line with this, the present study also indicated that Pro-GRP is a specific tumor marker of SCLC that had a relatively high expression prior to therapy and exhibited on obvious decrease thereafter.…”

“…Peripheral hematopoietic stem cells were expanded and DCs and CIKs were collected. The cell quantity was required to reach >1x10 10 and the cell activity >95%. The cells were suspended in 100 ml normal saline containing 20 g/l human serum albumin and injected back into the patient's body once per week for a total of three times.…”

Dendritic cell vaccine and cytokine-induced killer cell therapy for the treatment of advanced non-small cell lung cancer

“…A total of 1x10 7 DCs in 0.1 ml NS was administrated intradermally into the forearm of each patient. The patients were asked to measure the diameter of the skin erythema around the injection point following 24, 48 and 72 h. The DTH reaction was defined as follows: >10 mm in diameter, strongly positive; 5-10 mm, positive; 2-5 mm, weakly positive; and <2 mm, negative (22,28).…”

“…The supernatants were collected and used as a tumor lysate for DC preparation. DCs and CIK cells were prepared as described in a previous study (22)(23)(24). The supernatants of cultured PBMCs were removed for the additional preparation of CIK cells and the remaining cells were cultured for 7 days in the presence of granulocyte-macrophage colony stimulating factor, interleukin (IL)-4 and tumor necrosis factor (PeproTech EC, Ltd., London, UK), and pulsed with the tumor lysate (PeproTech EC, Ltd.) (25).…”

Clinical outcome of immunotherapy with dendritic cell vaccine and cytokine-induced killer cell therapy in hepatobiliary and pancreatic cancer

“…The cells were cultured overnight, then adherent cells (including monocytes) and suspension cells (including lymphocytes) were collected separately (14)(15)(16).…”