Enhanced antitumour immunity by combined use of temozolomide and TAT‐survivin pulsed dendritic cells in a murine glioma

Kim, Chang‐Hyun; Woo, Sun-Je; Park, Jungsun; Kim, Hye‐Sung; Park, Mi-Young; Park, Sung-Dong; Hong, Yong-Kil; Kim, Tai‐Gyu

doi:10.1111/j.1365-2567.2007.02680.x

Cited by 50 publications

(30 citation statements)

References 32 publications

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“…The considerable immune response rate may, moreover, reflect a beneficial effect of temozolomide. Several studies in mice have reported enhanced immunization after combining vaccination with temozolomide, or that temozolomide suppresses Treg function (4,(36)(37)(38)(39)(40). Chemotherapy may also suppress myeloid-derived suppressor cells (5).…”

Section: Discussionmentioning

confidence: 99%

Telomerase Peptide Vaccination Combined with Temozolomide: A Clinical Trial in Stage IV Melanoma Patients

Kyte

Gaudernack

Dueland

et al. 2011

Clinical Cancer Research

101

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Purpose: The study is a proof-of-principle trial evaluating toxicity, immune response, and clinical response in melanoma patients after combined therapy with temozolomide and the telomerase peptide vaccine GV1001. Our previous GV1001 trials showed immune responses in approximately 60% of lung or pancreatic cancer patients. Experimental Design: Twenty-five subjects with advanced stage IV melanoma (M1B or M1C) received concomitant temozolomide and GV1001. Temozolomide was administered 200 mg/m2 orally for 5 days every fourth week, and GV1001 as eight injections over 11 weeks. Immune response was evaluated by delayed type hypersensitivity, T-cell proliferation, and cytokine assays. The immunologic responders continued monthly vaccination. Results: The treatment was well tolerated. A GV1001-specific immune response was shown in 18 of 23 evaluated subjects (78%). Patients developing long-term T-cell memory survived more than those rapidly losing their responses. The immune response exhibited several characteristics of possible clinical significance including high IFNγ/IL-10 ratios, polyfunctional cytokine profiles, and recognition of naturally processed antigens. Survival compared favorably with matched controls from a benchmark meta-analysis (1 year: 44% vs. 24%, 2 years: 16% vs. 6.6%). The clinical responses developed gradually over years, contrary to what is expected from chemotherapy. Five patients developed partial tumor regression and six more recorded stable disease. One patient has no remaining disease on fluorodeoxyglucose positron emission tomography scans after 5 years. Conclusions: The immunologic response rate is considerable compared with previous GV1001 trials without concomitant chemotherapy, although low toxicity is retained. The results warrant further studies of GV1001/temozolomide treatment and support the general concept of combining cancer vaccination with chemotherapy. Clin Cancer Res; 17(13); 4568–80. ©2011 AACR.

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Section: Discussionmentioning

confidence: 99%

Telomerase Peptide Vaccination Combined with Temozolomide: A Clinical Trial in Stage IV Melanoma Patients

Kyte

Gaudernack

Dueland

et al. 2011

Clinical Cancer Research

101

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“…Although some objective responses were observed with increased tumor-free survival, the current adjunctive approaches are not curative. Thus, movement toward testing several modalities involving combinations of chemotherapy coupled with specific TAA peptide-pulsed DC vaccines has occurred [16]. Despite the fact that factors influencing the host immune response are poorly understood at this time, DC vaccination has emerged as a promising type of active immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

Tumor antigen precursor protein profiles of adult and pediatric brain tumors identify potential targets for immunotherapy

et al. 2008

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Objectives-We evaluated and compared tumor antigen precursor protein (TAPP) profiles in adult and pediatric brain tumors of 31 genes related to tumor associated antigens (TAA) for possible use in immunotherapy. Antigens were selected based on their potential to stimulate T cell responses against tumors of neuroectodermal origin.Methods-Thirty-seven brain tumor specimens from 11 adult and 26 pediatric patients were analyzed by quantitative real-time PCR for the relative expression of 31 TAPP mRNAs. The age range of adults (4F:7M) was 27-77 years (median 51.5 ± 14.5 years) and for pediatrics (12F:14M) was 0.9-19 years (median 8.3 ± 5.5 years). Histological diagnoses consisted of 16 glioblastomas, 4 low grade astrocytomas, 10 juvenile pilocytic astrocytomas, and 7 ependymomas.Results-The adult gliomas expressed 94% (29 of 31) of the TAPP mRNAs evaluated compared with pediatric brain tumors that expressed 55-74% of the TAPP mRNAs, dependent on tumor histological subtype. Four types of TAPP expression patterns were observed: (1) equal expression among adult and pediatric cases, (2) greater expression in adult than pediatric cases, (3) expression restricted to adult GBM and (4) a random distribution. The pediatric brain tumors lacked expression of some genes associated with engendering tumor survival, such as hTert and Survivin.Conclusions-The potential TAA targets identified from the TAPP profiles of 31 genes associated with adult and pediatric brain tumors may help investigators select specific target antigens for developing dendritic cell-or peptide-based vaccines or T cell-based immunotherapeutic approaches against brain tumors.

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“…The use of multimodality treatments that combine conventional antitumor therapies with immunotherapy, such as vaccination with DC-based vaccines, has emerged as a potentially plausible approach to the treatment of tumors (3,5). We previously reported that the use of a multimodality treatment regimen with a DC-based vaccine in combination with the chemotherapeutic agent temozolomide (TMZ) leads to enhanced tumor-specific CTL responses and enhanced antitumor effects, resulting in a cure rate higher than that achieved with either a DC-based vaccine or TMZ alone (17,28). However, the immunological factors relating to the antitumor effect of TMZ chemoimmunotherapy in a murine glioma model are still unclear.…”

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confidence: 99%

Immunological Factors Relating to the Antitumor Effect of Temozolomide Chemoimmunotherapy in a Murine Glioma Model

Kim¹,

Kim

Park³

et al. 2010

Clin Vaccine Immunol

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Most tumors express an array of antigens that act as targets for their immune-mediated destruction, and a number of potential therapies have emerged to exploit this (22). The immunotherapeutic strategy used to induce an immune response against tumors is quite attractive because it offers the potential for a high level of tumor-specific cytotoxicity, minimal side effects, and a durable effect.Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs) in the induction of primary immune responses (29, 33). Because of their central role in controlling cell-mediated immunity, DCs hold much promise as cellular adjuvants in therapeutic cancer vaccines. DC-based immunotherapy has been reported to induce strong antitumor immune responses in animal experiments and in selected clinical trials involving malignant gliomas (2, 11, 36). However, its clinical effects on patients with malignancies have not been up to the expectations because of immune tolerance, the sheer physical burden of tumor antigens, and the mechanisms of tumor escape from the immune surveillance system, among others (10,20).Calreticulin (CRT) acts as a danger signal for DCs, allowing them to phagocytose tumor cells and to prime tumor antigenspecific cytotoxic T cells (CTLs) (12). It was recently reported that CRT exposure on the surfaces of dying tumor cells may determine whether chemotherapy is immunogenic (26). The capacity of chemotherapies to induce immunogenic tumor cell death is associated with the expression of CRT on the tumor cell surface. Furthermore, it was shown with an animal tumor model that the provision of CRT from an exogenous CRT exposure source as enforcement for endogenous CRT exposure could improve the efficacy of chemotherapy by stimulating antitumor immunity (27). Thus, whether chemotherapy triggers such an immunogenic effect depends on the exposure of CRT on the cell surface. The use of multimodality treatments that combine conventional antitumor therapies with immunotherapy, such as vaccination with DC-based vaccines, has emerged as a potentially plausible approach to the treatment of tumors (3, 5). We previously reported that the use of a multimodality treatment regimen with a DC-based vaccine in combination with the chemotherapeutic agent temozolomide (TMZ) leads to enhanced tumor-specific CTL responses and enhanced antitumor effects, resulting in a cure rate higher than that achieved with either a DC-based vaccine or TMZ alone (17,28). However, the immunological factors relating to the antitumor effect of TMZ chemoimmunotherapy in a murine glioma model are still unclear.

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Enhanced antitumour immunity by combined use of temozolomide and TAT‐survivin pulsed dendritic cells in a murine glioma

Cited by 50 publications

References 32 publications

Telomerase Peptide Vaccination Combined with Temozolomide: A Clinical Trial in Stage IV Melanoma Patients

Telomerase Peptide Vaccination Combined with Temozolomide: A Clinical Trial in Stage IV Melanoma Patients

Tumor antigen precursor protein profiles of adult and pediatric brain tumors identify potential targets for immunotherapy

Immunological Factors Relating to the Antitumor Effect of Temozolomide Chemoimmunotherapy in a Murine Glioma Model

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