Immuno-viral therapy of brain tumors by combination of viral therapy with cancer vaccination using a replication-conditional HSV

Toda, Masahiro; Iizuka, Yukihiko; Kawase, Takeshi; Uyemura, Keiichi; Kawakami, Yutaka

doi:10.1038/sj.cgt.7700446

Cited by 38 publications

(24 citation statements)

References 33 publications

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“…[22][23][24]28 Moreover, we demonstrated that the antitumor effect on distant, noninfected tumors involves tumor antigen-specific CTL responses induced by the intratumoral HSV inoculation. 23 Although several brain tumor antigens have been recently identified, [38][39][40] few glioma antigens recognized by glioma-specific CTLs have been isolated.…”

Section: Discussionmentioning

confidence: 99%

“…20,21 For the induction of strong antitumor immune responses, we have used a replication-conditional HSV mutant, G207, to modify tumor cells directly in situ. [22][23][24][25][26] Using syngeneic tumor models with mouse CT26 colon adenocarcinoma cells, we have demonstrated that intratumoral inoculation with G207 elicits strong immune responses not only to the HSV but also to the tumor antigen. 23,24 Inoculation with G207 inhibits the growth of both the infected tumor and the noninfected contralateral tumor.…”

mentioning

confidence: 99%

“…[22][23][24][25][26] Using syngeneic tumor models with mouse CT26 colon adenocarcinoma cells, we have demonstrated that intratumoral inoculation with G207 elicits strong immune responses not only to the HSV but also to the tumor antigen. 23,24 Inoculation with G207 inhibits the growth of both the infected tumor and the noninfected contralateral tumor. Mice treated intratumorally with G207 generate specific CTL responses against CT26 as well as the AH1 peptide, 27 the immunodominant MHC class I-restricted antigen for CT26.…”

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confidence: 99%

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Identification of a glioma antigen, GARC‐1, using cytotoxic T lymphocytes induced by HSV cancer vaccine

Iizuka¹,

Kojima²,

Kobata³

et al. 2005

Intl Journal of Cancer

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Despite several ongoing clinical trials of immunotherapies against glioma, few glioma-specific antigens recognized by cytotoxic T lymphocytes (CTLs) have been identified. We recently demonstrated that intratumoral inoculation with herpes simplex virus (HSV) as a cancer vaccine activates tumor-specific CTLs. To identify glioma antigens recognized by CTLs, we used the HSV cancer vaccine to vaccinate mice harboring a syngeneic mouse glioma cell line, GL261. From the splenocytes of the immunized mice, we generated an H-2D b -restricted CTL line, GCL-1, that was specific for GL261. Then, a cDNA expression library generated from GL261 was screened with GCL-1, and a new gene encoding glioma antigen, GARC-1, was isolated. Sequence analysis revealed that the GARC-1 gene isolated from GL261 had a point mutation causing an amino acid change (Asp to Asn at position 81). T-cell epitope analysis revealed that the mutated peptide GARC-1 77-85 (AALLN-KLYA) but not the wild-type peptide (AALLDKLYA), was recognized by GCL-1. These results suggest that HSV cancer vaccination may be a useful method for inducing tumor-specific CTLs and identifying tumor antigens. Furthermore, this GL261/ GARC-1 murine glioma model may be useful for the development of immunotherapy for brain tumors. ' 2005 Wiley-Liss, Inc.Key words: glioma; antigen; CTL; immunotherapy; HSV; G207; GL261; cancer vaccine Malignant brain tumors continue to be a major unsolved health problem throughout the world. Despite aggressive combined treatment modalities, little improvement has been made in the prognosis and survival of patients with malignant gliomas over the last decade. [1][2][3] The standard management of patients with malignant gliomas entails surgical resection followed by radiotherapy and chemotherapy. However, tumor progression inevitably occurs in almost all patients. 4 Therefore, the development of new therapeutic modalities for malignant gliomas is needed.Although the central nervous system (CNS) has long been considered an immunologically privileged site, recent studies have demonstrated that this privileged state is not absolute. [5][6][7][8] The presence of active immunity within the CNS supports the possibility of manipulating the immune system to create effective immunotherapy protocols against gliomas. 9,10 Recent progress in tumor immunology has highlighted the molecules involved in specific tumor immunity, including tumor rejection antigens recognized by CTLs. 11-15 Some of the antigenic peptides encoded by the tumor antigen genes have been used as a peptide-based vaccine in clinical trials for cancer patients, with tumor regression observed in some melanoma patients. 16,17 Despite several ongoing clinical trials of immunotherapies against glioma, however, few glioma antigens recognized by CTLs have been identified. To better understand the immune responses in the CNS and to design immunotherapeutic strategies against gliomas, glioma-specific antigens must be identified.A number of lytic viruses have been used in attempts to induce antitumor imm...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Identification of a glioma antigen, GARC‐1, using cytotoxic T lymphocytes induced by HSV cancer vaccine

Iizuka¹,

Kojima²,

Kobata³

et al. 2005

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

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“…178,179 It appears that G207 inhibits tumor growth by two mechanisms: direct oncolysis via virus replication 166 and induction of tumor-specific immunity via an increase in cytotoxic T-cell (CTL) activity. 172,[180][181][182][183] Based on the promising preclinical data, G207 is now evaluated in clinical trials. Phase I clinical trials in patients with malignant glial tumors confirmed the safety of G207 virotherapy.…”

Section: Hsv-1 For Cancer Treatment Y Shen and J Nemunaitismentioning

confidence: 99%

Herpes simplex virus 1 (HSV-1) for cancer treatment

2006

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Cancer remains a serious threat to human health, causing over 500 000 deaths each year in US alone, exceeded only by heart diseases. Many new technologies are being developed to fight cancer, among which are gene therapies and oncolytic virotherapies. Herpes simplex virus type 1 (HSV-1) is a neurotropic DNA virus with many favorable properties both as a delivery vector for cancer therapeutic genes and as a backbone for oncolytic viruses. Herpes simplex virus type 1 is highly infectious, so HSV-1 vectors are efficient vehicles for the delivery of exogenous genetic materials to cells. The inherent cytotoxicity of this virus, if harnessed and made to be selective by genetic manipulations, makes this virus a good candidate for developing viral oncolytic approach. Furthermore, its large genome size, ability to infect cells with a high degree of efficiency, and the presence of an inherent replication controlling mechanism, the thymidine kinase gene, add to its potential capabilities. This review briefly summarizes the biology of HSV-1, examines various strategies that have been used to genetically modify the virus, and discusses preclinical as well as clinical results of the HSV-1-derived vectors in cancer treatment.

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“…43 This is in accordance with the observation that following intratumoral injection of so called oncolytic herpesvirus vectors for local tumor control, systemic antitumor activity with rejection of metastases at distant sites has been observed. 44 In this setting HSV vector-induced lysis of solid tumor cells is thought to initiate crosspriming events, [45][46][47] resulting in uptake of tumor-cell-derived proteins by professional antigen-presenting cells. 48 The observed expansion of activated T, NK and antigen-presenting cells in mice splenocytes supports a similar scenario underlying the antineoplastic effects induced by the replication-defective HSV-1 helper virus-dependent vectors.…”

Section: Hsv-1 Amplicons For Generation Of All Vaccinesmentioning

confidence: 99%

Herpes simplex virus type-1 amplicon vectors for vaccine generation in acute lymphoblastic leukemia

et al. 2005

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For leukemia vaccine generation, high-efficiency gene transfer is required to express immunomodulatory molecules that stimulate potent antileukemic immune responses. In this context, herpes simplex virus type-1 (HSV-1)-derived vectors have proven to be a promising tool for genetic modification of lymphoblastic leukemia cells. Yet, vector-associated viral protein expression might inadvertently modulate vaccine efficacy facilitating both immune evasion and immune stimulation. To explore the issue of immune-stimulation versus immune-suppression in immature lymphoblastic leukemia cells, two types of HSV-1 amplicon vectors, helper virus-dependent and helper virus-free that express the immunomodulatory molecules CD70 and IL-2, were compared with regard to their vector-associated immunomodulatory potential. We first established that lymphoblastic cell lines and primary acute lymphoblastic leukemia (ALL) cells express HSV receptor genes. Lymphoblastic cell lines were transduced with high efficiency, and in primary ALL cells high gene transfer rates of 47715 and 42714% were obtained with helper virus-dependent and -free HSV-1 amplicon vectors, respectively. The efficacy of the two amplicon vectors to induce antineoplastic responses was assessed in a vaccine setting in mice with pre-existing highly malignant lymphoblastic disease. Treatment of mice with vaccine cells transgenically expressing CD70+IL2 significantly suppressed lymphoblastic cell proliferation and improved survival. Of note, when helper virus-dependent HSV-1 amplicon vectors were used for vaccine preparation, the high immunogenic potential of the vector itself, in the absence of transgenic CD70+IL2 expression, seemed to be sufficient to mediate protection comparable to the antineoplastic response achieved by expression of immunomodulatory molecules. Thus for vaccine generation in B lymphoblastic leukemia, the immunogenic potential of HSV-1 helper virus-dependent amplicon vectors does provide additional benefit to the high transduction efficiency of HSV-1-derived vectors.

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Immuno-viral therapy of brain tumors by combination of viral therapy with cancer vaccination using a replication-conditional HSV

Cited by 38 publications

References 33 publications

Identification of a glioma antigen, GARC‐1, using cytotoxic T lymphocytes induced by HSV cancer vaccine

Identification of a glioma antigen, GARC‐1, using cytotoxic T lymphocytes induced by HSV cancer vaccine

Herpes simplex virus 1 (HSV-1) for cancer treatment

Herpes simplex virus type-1 amplicon vectors for vaccine generation in acute lymphoblastic leukemia

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