Phase I clinical trial of a five-peptide cancer vaccine combined with cyclophosphamide in advanced solid tumors

Murahashi, Mutsunori; Hijikata, Yasuki; Yamada, Kazunari; Tanaka, Yoshihiro; Kishimoto, Junji; Inoue, Hiroyuki; Marumoto, Tomotoshi; Takahashi, Atsushi; Okazaki, Toshihiko; Takeda, Kazuyoshi; Hirakawa, Masakazu; Fujii, Hiroshi; Okano, Shinji; Morita, Masaru; Baba, Eishi; Mizumoto, Kazuhiro; Maehara, Yoshihiko; Tanaka, Masao; Akashi, Koichi; Nakanishi, Yoichi; Yoshida, Kōji; Tsunoda, Takuya; Tamura, Kazuo; Nakamura, Yusuke; Tani, Kenzaburo

doi:10.1016/j.clim.2016.03.015

Cited by 53 publications

(32 citation statements)

References 43 publications

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“…We also showed that FoxM1 was overexpressed in GC and its overexpression was a significant prognostic factor and had an association with chemo-resistance in GC (28). Upregulated lung cancer 10 (URLC10), KIF20 and DEPDC1, which have been used for cancer vaccine therapy as oncogenic peptides (29)(30)(31), were also confirmed to show overexpression in GC. A vaccination with a peptide derived from vascular endothelial growth factor receptor-1 (VEGFR-1) has also been reported to show cytotoxicity for tumors as an antiangiogenic cancer vaccine (32).…”

Section: Multiple Therapeutic Peptide Vaccines For Patients With Advamentioning

confidence: 55%

“…FoxM1 is a well-studied molecule associated with cancer development, and we have reported that its overexpression makes it worth consideration as a prognostic marker in GC (28). DEPDC1, kIF20 and URLC10 were also reported as cancerspecific antigens and have been applied in peptide vaccination therapy (29)(30)(31)(34)(35)(36). An anti-angiogenic vaccine targeting VEGFR-1 was also widely studied in patients with advanced solid tumors (29,32).…”

Section: Discussionmentioning

confidence: 99%

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Multiple therapeutic peptide vaccines for patients with advanced gastric cancer

Fujiwara

Okada

Omori

et al. 2017

International Journal of Oncology

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We performed a clinical trial using HLA-A24-binding peptide vaccines containing a combination of novel cancer-testis antigens and anti-angiogenic peptides for advanced gastric cancer (GC). Thirty-five GC patients who had shown resistance to the standard therapy were enrolled in this clinical trial using vaccinations with a mixture of multiple peptides derived from DEPDC1, URLC10, FoxM1, Kif20A and VEGFR1. The safety, the overall survival (OS), and the immunological responses based on an ELISPOT assay were determined to assess differences in patients who were HLA-A24-positive [24(+)] and HLA-A24-negative [24(-)]. No severe adverse effects were observed except for severe skin reactions in 4 patients. The differences in OS were not significant between patients who were 24(+) and 24(-). In the 24(+) group, patients who showed T cell responses specific to antigen peptides had a tendency towards better survival than those who showed no response, especially to the DEPDC1 peptide. The patients with local skin reactions had significantly better OS than the others. Peptide vaccine therapy was found to be safe and is expected to induce specific T cell responses in patients with advanced GC. The survival benefit of peptide vaccine monotherapy may not have been shown and further trials are needed to confirm these results.

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Section: Multiple Therapeutic Peptide Vaccines For Patients With Advamentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Multiple therapeutic peptide vaccines for patients with advanced gastric cancer

Fujiwara

Okada

Omori

et al. 2017

International Journal of Oncology

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“…238 Murahashi et al (from Kyushu University, Fukuoka, Japan) evaluated a multipeptide-based vaccine combined with escalating doses of cyclophosphamide in patients with locally advanced, metastatic and/or recurrent gastrointestinal, lung or cervical cancer, achieving increased overall survival accompanied by increased TAA-specific T cells and peripheral T REG cell depletion. 242 Tanis and collaborators (from The Netherlands Cancer Institute, Amsterdam, Netherlands) found that patients with liver metastases from colorectal carcinoma obtain a survival benefit from the FOLFOX therapeutic regimen (consisting of folinic acid, fluorouracil and oxaliplatin), which is accompanied by increased amount of CTLs at invasive tumor margin, as well as with mast cell infiltration. 243 Collectively, these reports demonstrate that ICDinducing chemotherapeutic regimens can prolong the survival of some cancer patients, and this often correlates with biomarkers of ongoing anticancer immunity.…”

Section: Completed Clinical Trialsmentioning

confidence: 99%

Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

et al. 2017

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The expression "immunogenic cell death" (ICD) refers to a functionally unique form of cell death that facilitates (instead of suppressing) a T cell-dependent immune response specific for dead cell-derived antigens. ICD critically relies on the activation of adaptive responses in dying cells, culminating with the exposure or secretion of immunostimulatory molecules commonly referred to as "damage-associated molecular patterns". Only a few agents can elicit bona fide ICD, including some clinically established chemotherapeutics such as doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin. In this Trial Watch, we discuss recent progress on the development of ICD-inducing chemotherapeutic regimens, focusing on studies that evaluate clinical efficacy in conjunction with immunological biomarkers.

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“…Several studies suggest that the optimal time point for vaccination is 3-7 days after this type of chemotherapy [50][51][52]. In a randomized phase II trial, administration of a single dose of cyclophosphamide, followed by vaccination 3 days later with IMA901, a vaccine that consists of multiple-tumor associated peptides (TUMAPs) plus granulocyte-macrophage colony-stimulating factor (GM-CSF), reduced the number of Tregs and was associated with prolonged survival in immune responder patients with advanced renal cell cancer [52].…”

Section: Administration Of Chemotherapy Before Vaccination Alleviatesmentioning

confidence: 99%

The importance of correctly timing cancer immunotherapy

Nejad

Welters

Arens

et al. 2016

Expert Opinion on Biological Therapy

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Introduction:The treatment options for cancer-surgery, radiotherapy and chemotherapy-are now supplemented with immunotherapy. Previously underappreciated but now gaining strong interest are the immune modulatory properties of the three conventional modalities. Moreover, there is a better understanding of the needs and potential of the different immune therapeutic platforms. Key to improved treatment will be the combinations of modalities that complete each other's shortcomings. Area covered: Tumor-specific T-cells are required for optimal immunotherapy. In this review, the authors focus on the correct timing of different types of chemotherapeutic agents or immune modulators and immunotherapeutic drugs, not only for the activation and expansion of tumor-specific Tcells but also to support and enhance their anti-tumor efficacy. Expert opinion: At an early phase of disease, clinical success can be obtained using single treatment modalities but at later disease stages, combinations of several modalities are required. The gain in success is determined by a thorough understanding of the direct and indirect immune effects of the modalities used. Profound knowledge of these effects requires optimal tuning of immunomonitoring. This will guide the appropriate combination of treatments and allow for correct sequencing the order and interval of the different therapeutic modalities. ARTICLE HISTORY

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Phase I clinical trial of a five-peptide cancer vaccine combined with cyclophosphamide in advanced solid tumors

Cited by 53 publications

References 43 publications

Multiple therapeutic peptide vaccines for patients with advanced gastric cancer

Multiple therapeutic peptide vaccines for patients with advanced gastric cancer

Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

The importance of correctly timing cancer immunotherapy

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