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Lot 006; Thermo Fisher Scientific, Inc. The PCR amplified products were examined by agarose gel electrophoresis, and the results were observed under a UV lamp and photographed. ZA-0063; 1:100; and vascular endothelial growth factor receptor 2 (VEGFR-2) primary antibody, rabbit anti-human polyclonal antibody; cat. ZA-0287; 1:100; Beijing Zhongshan Jinqiao Biotechnology Co.

Slices were the incubated with horseradish peroxidase-conjugated secondary goat anti-rabbit antibody (cat. Expression of these proteins was evaluated using optical microscopy (BX43; Olympus Corporation, Tokyo, Japan) as positive when the nucleus of the cancerous tissue was stained. Positive controls (tissues known to be positive for antigen expression) and negative controls (replaced primary antibody with normal rabbit (rat) serum and the result was negative) were included in each run.

Results demonstrated overexpression of CEA and VEGFR-2. CEA-652 peptide (TYACFVSNL; cat. In vitro cell processing and expansion were performed in a good manufacturing practices-compliant laboratory. DCs and CTLs were obtained from blood mononuclear cells as described previously (12,13). Cell counts were estimated using the trypan blue dye-exclusion method (14). The average cell count of PBMCs prior to each expansion was 2.

FACS Ariar cell sorter (BD Biosciences) was used to perform fluorescent expression analysis. Data were analyzed using FlowJo software 7. Prior to cell transplantation, cells were tested for endotoxin levels using a Limulus Amebocyte Lysate kit (Charles River Laboratories, Ltd. Plates were scanned using an Elispot CTL Reader (Cell Technology Inc. CTL, cytotoxic T lymphocyte; CD, cluster of differentiation; PE, phycoerythrin; FITC, fluorescein isothiocyanate. The patient received 8 cycles of antigen peptide-pulsed DC-CTLs with an oral administration of low-dose of cyclophosphamide (50 mg daily) from June 2014 to May 2015.

Each cycle included the administration of two DC vaccines (1. The DCs and CTLs were administered intradermally and intravenously, respectively.

Throughout the course of treatment, the progression of the metastatic bone lesions was monitored using CT, MRI and ECT. Positive CTL responses specific to the vaccinated peptides were determined as previously described (10). IFN, interferon; PBMC, peripheral blood mononuclear cell; CEA, carcinoembryonic antigen; VEGFR-2, vascular endothelial growth factor receptor 2; ELISPOT, enzyme-linked immunospot. Following 3 cycles of treatment, CT scan demonstrated a decrease in multiple patchy high-density shadows located in the pelvis (Fig.

The radionuclide bone-imaging scan indicated a marked decrease in the number of multiple bone metastases (Fig. Following completion of 8 cycles of autologous immune enhancement therapy, the number of multiple bone metastases was markedly decreased, this was further confirmed in June 2015 using CT imaging (Fig. Overall, the patient was doing well at the time of writing. The present case was the first report of the disappearance of almost all bone metastases following antigen peptide-pulsed DC-CTLs immunotherapy in chemotherapy-resistant gastric cancer.

We also investigated the safety and efficacy of the ex vivo activated, expanded and adoptively transferred antigen peptide-pulsed DC-CTLs obtained from the peripheral blood of a stage IV chemotherapy-resistant patient with GC and multiple bone metastases, whose bone metastases was markedly decreased following therapy and without serious adverse reactions.

As an immune-based approach, adoptive therapy has become an increasingly attractive modality for cancer therapy due to collectively demonstrating a decreased risk of cross-resistance compared with conventional therapies, high specificity and long-term immune protection (15). Recent success of adoptive T cell therapy using ex vivo expanded autologous tumor-reactive T cells has increased optimism that this modality may form a specific therapy for patients with advanced-stage disease, including those who are refractory to standard therapies (16,17).

Previously, autologous immune cells intravenously administered to patients with GC have resulted in improved survival rates compared with controls, as reported by Zhang et al (18).

CEA and VEGFR-2 are the most commonly expressed antigens in GC. Over the course of an adoptive cell transfer, monitoring antigen-specific T cell expansion in patient blood is crucial for predicting the clinical efficacy of such an immunological approach. The patient was administered with ex vivo generated CEA- and VEGFR-2-specific CTLs.

A previous study demonstrated that cyclophosphamide exerted variable effects on depleting suppressive Tregs, which resulted in enhanced T cell reactivity (22). Research also demonstrated that cyclophosphamide at a low dose selectively depleted Tregs, whereas at a high dose, cyclophosphamide led to a loss in specificity of Treg depletion in patients with cancer (23). Using this strategy, marked clinical benefits have been obtained, such as a significant delay in tumor progression.

In the present case report, oral administration of low-dose cyclophosphamide accompanied by immune cell transfusions resulted in the almost complete disappearance of all multiple bone metastases in chemotherapy-resistant GC, which lasted for over one year.

Therefore, optimizing the combination of adoptive cellular therapy and other immune-based or conventional approaches may herald a new generation of research and clinical opportunities for cancer immunotherapy. In conclusion, specific antigen peptide-pulsed DC-CTLs combined with low-dose cyclophosphamide administered to the patient with stage IV chemotherapy-resistant GC, demonstrated its safety by not exhibiting any severe adverse reactions.

There was also a marked decrease in bone metastatic lesions, improved quality of life and a prolonged duration of progression-free survival over one year. Therefore, it is recommended that the adoptive transfer of personalized antigen peptide-pulsed DC-CTLs may serve as a promising specific immunotherapy strategy for patients with malignant disease, and may be considered in combination with oral administration of low-dose cyclophosphamide or other modalities of treatment in cases of a similar nature.

The authors acknowledge the financial support from National Natural Science Foundation of China (grant nos. The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. JD and BL undertook study conception and design. JD, JW, YY, SS, JS, FC, FM and BL were responsible for the collection and assembly of data: Data analysis and interpretation were the responsibilities of JD, SS, JS, FC, FM, ZZ and BL.

JD wrote the manuscript. Final approval of manuscript was given by JD, JW, YY, SS, JS, FC, FM, ZZ and BL. Study participants provided written informed consent. World J Gastrointest Oncol. View Article : Google Scholar15 Wang M, Yin B, Wang HY and Wang RF: Current advances in T-cell-based cancer immunotherapy. To find out more, you may read our Privacy Policy. Following 3 cycles of combination therapy, marked remission regarding the number of metastatic bone lesions was achieved, confirmed by the use of enhanced computerized tomography, computerized tomography and magnetic resonance imaging.

Introduction Gastric cancer (GC) is the second most frequent cause of cancer-associated mortality in China (1). Case report Patient history Written informed consent was obtained from the patient for publication of the present case report and any accompanying results. Oncol Lett 16: 875-881, 2018Du, J.

Oncology Letters, 16, 875-881. Oncology Letters 16, no. View Article : Google Scholar 15 Wang M, Yin B, Wang HY and Wang RF: Current advances in T-cell-based cancer immunotherapy. The lymph nodes are an important gateway in the formation of metastatic cancer, as they take in cancer cells and then spew them out into the body, where they can form new tumors in distant tissues.

Now, scientists led by the Dartmouth-Hitchcock Medical Center have discovered T cells in the lymph nodes that have the power to kill melanoma cells before they can spread-a potential new target for therapeutic development. Unlike typical T cells that travel freely throughout the body, the cells the Dartmouth team discovered stay in the lymph nodes and kill melanoma cells.

The team treated mouse models of melanoma with immunotherapy, then injected resident memory T cells into them a month later. The melanoma did not return, they reported. They went on to analyze the gene signatures of T cells in melanoma samples from the Cancer Genome Atlas. The presence of resident memory T cells correlated with positive patient outcomes and longer survival in melanoma patients with lymph node metastases, the researchers reported. The researchers used advanced genetic sequencing techniques to determine that the primary job of the T cells they identified is to fend off cancer in the lymph nodes.

Immunotherapy has been game-changing in the treatment of melanoma, but not all patients respond well to it, inspiring many research teams to uncover mechanisms of resistance.