Xenogeneic immunization with human tyrosine hydroxylase DNA vaccines suppresses growth of established neuroblastoma

Huebener, Nicole; Fest, Stefan; Hilt, Kerstin; Schramm, Alexander; Eggert, Angelika; Durmus, Tahir; Woehler, Anja; Stermann, Alexander; Bleeke, Matthias; Baykan, Bianca; Weixler, Silke; Gaedicke, Gerhard; Lode, Holger N.

doi:10.1158/1535-7163.mct-09-0107

Cited by 25 publications

(15 citation statements)

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“…Additionally, the immune response against H9 could lead to antigenic spread to induce protective immunity against NuTu-19 unique tumor antigens, a concept akin to what was proposed to explain the efficiency of xenogeneic antigen immunization. (Huebener et al, 2009) We have found cross-reactive proteins between H9 and NuTu-19 by Western-blot. The ability to separate and purify these proteins in order to find the exact antigen and to explore the antitumor mechanism of embryonic stem cells are both interesting questions worthy of further exploration.…”

Section: Discussionmentioning

confidence: 77%

Human Embryonic Stem Cells - a Potential Vaccine for Ovarian Cancer

Zhang

Chen²,

Chang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Section: Discussionmentioning

confidence: 77%

Human Embryonic Stem Cells - a Potential Vaccine for Ovarian Cancer

Zhang

Chen²,

Chang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…Vaccination of mice with tyrosine hydroxylase DNA minigenes can induce CTLs, eradicate established primary NXS2 neuroblastoma tumors, and inhibit spontaneous metastases without induction of autoimmunity (29, 30). MYCN derived peptides have been reported to generate MHC class I restricted human CTL in vitro that lyse MYCN amplified human neuroblastoma cells (31).…”

Section: Cytotoxic T Lymphocytesmentioning

confidence: 99%

Immunology and immunotherapy of neuroblastoma

Seeger

2011

Seminars in Cancer Biology

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Purpose This review demonstrates the importance of immunobiology and immunotherapy research for understanding and treating neuroblastoma. Principal results The first suggestions of immune system-neuroblastoma interactions came from in vitro experiments showing that lymphocytes from patients were cytotoxic for their own tumor cells and from evaluations of tumors from patients that showed infiltrations of immune system cells. With the development of monoclonal antibody (mAb) technology, a number of mAbs were generated against neuroblastoma cells lines and were used to define tumor associated antigens. Disialoganglioside (GD2) is one such antigen that is highly expressed by virtually all neuroblastoma cells and so is a useful target for both identification and treatment of tumor cells with mAbs. Preclinical research using in vitro and transplantable tumor models of neuroblastoma has demonstrated that cytotoxic T lymphocytes (CTLs) can specifically recognize and kill tumor cells as a result of vaccination or of genetic engineering that endows them with chimeric antigen receptors. However, CTL based clinical trials have not progressed beyond pilot and phase I studies. In contrast, anti-GD2 mAbs have been extensively studied and modified in pre-clinical experiments and have progressed from phase I through phase III clinical trials. Thus, the one proven beneficial immunotherapy for patients with high-risk neuroblastoma uses a chimeric anti-GD2 mAb combined with IL-2 and GM-CSF to treat patients after they have received intensive cyto-reductive chemotherapy, irradiation, and surgery. Ongoing pre-clinical and clinical research emphasizes vaccine, adoptive cell therapy, and mAb strategies. Recently it was shown that the neuroblastoma microenvironment is immunosuppressive and tumor growth promoting, and strategies to overcome this are being developed to enhance anti-tumor immunotherapy. Conclusions Our understanding of the immunobiology of neuroblastoma has increased immensely over the past 40 years, and clinical translation has shown that mAb based immunotherapy can contribute to improving treatment for high-risk patients. Continued immunobiology and pre-clinical therapeutic research will be translated into even more effective immunotherapeutic strategies that will be integrated with new cytotoxic drug and irradiation therapies to improve survival and quality of life for patients with high-risk neuroblastoma.

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“…Another pre-clinical study have demonstrated that tyrosine hydroxylase and MYCN proteins, which are relatively specific for neuroblastoma cells compared to normal cells, include peptides that can be targets for CTL. Vaccination of mice with tyrosine hydroxylase DNA minigenes can induce CTLs, eradicate established primary NXS2 neuroblastoma tumors, and inhibit spontaneous metastases without induction of autoimmunity [84,85].…”

Section: Cd8mentioning

confidence: 99%