Clinical Evaluation of Dendritic Cells Vaccination for Advanced Cancer Patients at Fukushima Medical University

Nakamura, Izumi; Kanazawa, Masashi; Sato, Yu; Irisawa, Atsushi; Takagi, Tadayuki; Ogata, Takashi; Kashimura, Shogo; Kenjo, Akira; Suzuki, Hiroyuki; Shibata, Masahiko; Shimura, Tatsuo; Ohira, Hiromasa; Goto, Minoru; Takenoshita, Seiichi; Ohto, Hitoshi

doi:10.5387/fms.58.40

Cited by 9 publications

(5 citation statements)

References 16 publications

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“…Thus, it has been suggested that in clinical trials, in order to obtain enhanced vaccine efficiency, peptide-pulsed DCs are immunized mostly via s.c. or i.d. [52][53][54][55][56]. In further studies, a comparison on i.p.…”

Section: Discussionmentioning

confidence: 99%

Enhanced anti-colon cancer immune responses with modified eEF2-derived peptides

et al. 2015

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A B S T R A C TEukaryotic elongation factor-2 (eEF2) is overexpressed in many human cancers and is an attractive target for cancer immunotherapy. The eEF2 derived polypeptides have been shown to be able to induce cytotoxic T lymphocytes from healthy donor. Here, we demonstrate the evidence indicating that modification of a segment of peptides from wild type eEF2-derived immunogenic peptides is able to further enhance its capacity of inducing antigen-specific cytotoxic T lymphocytes (CTLs) against colon cancer cells. Using peptide-MHC binding algorithms, potential HLA-A2.1-restricted epitopes capable of inducing specific CD8 + CTLs were identified. By analyzing HLA-A2.1 affinity and immunogenicity, we further identified one novel immunogenic peptide, P739-747 (RLMEPIYLV), that elicited specific CTL responses in HLA-A2.1/K b transgenic mice and culture with peripheral blood lymphocytes from colon cancer patients. Furthermore, replacing certain amino acids (at positions 1, 3, 7) within the P739-747 sequence improved the immunogenicity against eEF2. Several analogs containing the auxiliary HLA-A*0201 anchor residues were able to stably bind to HLA-A*0201 and enhance CTL responses compared with the native sequence; two of them showed increased anti-tumor effects during the adoptive immunotherapy in vivo. Thus, these results support that modified immunogenic analogs are promising candidates for peptide-based cancer vaccination and immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Enhanced anti-colon cancer immune responses with modified eEF2-derived peptides

et al. 2015

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“…Endoscopic ultrasonography–fine needle aspiration biopsy has recently made remarkable progress. For example, the direct injection of immature dendritic cells into advanced pancreatic tumors using an EUS‐guided fine‐needle injection technique has been reported, and CRAds could potentially be injected directly into pancreatic cancers using this method. Intravenously injected CRAds were also found to be safe in the infection of cancer cells and to replicate and emit light in vivo .…”

Section: Discussionmentioning

confidence: 99%

Conditionally replicative adenoviral vectors for imaging the effect of chemotherapy on pancreatic cancer cells

et al. 2013

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Pancreatic cancer has a poor prognosis after complete macroscopic resection combined with chemotherapy. Even after neoadjuvant chemotherapy, R0 resection is often not possible. Moreover, current imaging techniques cannot reliably distinguish viable cancer cells from scar tissue at the resectional margin. We investigated the use of a conditionally replicative adenovirus (CRAd), Ad5 ⁄ 3Cox2CRAd-DE3ADP-Luc, for imaging the effects of chemotherapy. The CRAd infectivity of pancreatic cancer cells was enhanced by a chimeric Ad5 ⁄ 3 fiber, E1A expression was under the control of the Cox2 promoter, and the luciferase gene was inserted adjacent to the adenovirus death protein (ADP) gene. Subcutaneous xenografts of the pancreatic cancer cell line MiaPaCa-2 were established in 24 BALB ⁄ c nu ⁄ nu mice. When xenografts reached a diameter of 4-6 mm (day 1), the mice were injected i.p. with either PBS (group A; n = 12) or 1000 mg ⁄ kg gemcitabine (group B; n = 12), weekly. On days 19, 26, 33, and 40, CRAd were injected intratumorally into three mice in groups A and B. Bioluminescence was imaged 72 h after CRAd injection, and gross tumor volumes were measured then tumors were removed for ex vivo histopathology using H&E and Ki-67 staining. Correlations between gross tumor volume, pathological evaluation of the percentage of viable tumor area, and CRAd bioluminescence were analyzed. Bioluminescence correlated closely with the percentage of viable tumor area (R = 0.96), but not with gross tumor volume (R = 0.31). Therefore, CRAds might be reliable imaging tools for monitoring chemotherapy in pancreatic cancer, and could improve our ability to distinguish viable tumor cells from scar tissue. (Cancer Sci 2013; 104: 1083-1090 P ancreatic adenocarcinoma has one of the worst survival rates of all cancers worldwide, with only a 5% five-year survival rate, for all stages. In 2008, 37 680 new cases of pancreatic cancer were diagnosed, and 34 290 deaths were expected.(1) In Japan, only 20% of patients diagnosed with pancreatic cancer are treatable by resection, as 50-60% of patients already have distant metastases and approximately 30% of patients have locally advanced disease that is not resectable.(2) Median survival rates of 20-24 months can be expected only in cases where resection is possible and is combined with postoperative chemotherapy or chemoradiation. (3)(4)(5)

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“…DCs pulsed by peptide and injected into the skin showed a response rate of 28%. This percentage increased to 35.7% when immature DCs are injected straight into the tumour and even higher to 40% for advanced pancreatic cancer [113].…”

Section: Modes Of Immunotherapymentioning

confidence: 97%