B7.1 immunogene therapy effectively activates CD4+ tumor-infiltrating lymphocytes in the central nervous system in comparison with B7.2 gene therapy

Ando, Hideyuki; Saio, Masanao; Ohe, Naoyuki; Tamakawa, Noriyuki; Yu, Hai; Nakayama, Takashi; Yoshimura, Shinichi; Kaku, Yasuhiko; Iwama, Toru; Shinoda, Jun; Sakai, Noboru; Takami, Taro

doi:10.3892/ijo.20.4.807

Cited by 8 publications

(7 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This was thought would circumvent the necessity of dendritic cells to first activate naïve T-cells. In a mouse model of glioma, it was found that B7.1 expression on tumor cells within the CNS was sufficient to improve survival in 60% animals for longer than 120 days [151]. Survival was significantly greater than animals injected with wild-type tumor cells, which survived for less than 20 days.…”

Section: Dendritic Cellsmentioning

confidence: 95%

“…Survival was significantly greater than animals injected with wild-type tumor cells, which survived for less than 20 days. However, the tumor model used in this study was injected into the subarachnoid space, a region of the brain with a large number of infiltrating immune cells, including T-cells and dendritic cells [151]. In two separate studies, one using transfected glioma cells and the other using adenovirus expressing the B7.1 transgene to infect glioma cells in vitro before intracranial implantation, a very weak anti-tumor response was observed This suggests that B7.1 expression alone is not sufficient to induce strong anti-tumor immunity against brain tumors [152,153], most likely because priming of naïve T lymphocytes normally occurs within the microenvironment of the lymph nodes.…”

Section: Dendritic Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Combining Cytotoxic and Immune-Mediated Gene Therapy to Treat Brain Tumors

Curtin

King

Candolfi

et al. 2005

CTMC

View full text Add to dashboard Cite

Glioblastoma (GBM) is a type of intracranial brain tumor, for which there is no cure. In spite of advances in surgery, chemotherapy and radiotherapy, patients die within a year of diagnosis. Therefore, there is a critical need to develop novel therapeutic approaches for this disease. Gene therapy, which is the use of genes or other nucleic acids as drugs, is a powerful new treatment strategy which can be developed to treat GBM. Several treatment modalities are amenable for gene therapy implementation, e.g. conditional cytotoxic approaches, targeted delivery of toxins into the tumor mass, immune stimulatory strategies, and these will all be the focus of this review.Both conditional cytotoxicity and targeted toxin mediated tumor death, are aimed at eliminating an established tumor mass and preventing further growth. Tumors employ several defensive strategies that suppress and inhibit anti-tumor immune responses. A better understanding of the mechanisms involved in eliciting anti-tumor immune responses has identified promising targets for immunotherapy. Immunotherapy is designed to aid the immune system to recognize and destroy tumor cells in order to eliminate the tumor burden. Also, immune-therapeutic strategies have the added advantage that an activated immune system has the capability of recognizing tumor cells at distant sites from the primary tumor, therefore targeting metastasis distant from the primary tumor locale. Pre-clinical models and clinical trials have demonstrated that in spite of their location within the central nervous system (CNS), a tissue described as 'immune privileged', brain tumors can be effectively targeted by the activated immune system following various immunotherapeutic strategies. This review will highlight recent advances in brain tumor immunotherapy, with particular emphasis on advances made using gene therapy strategies, as well as reviewing other novel therapies that can be used in combination with immunotherapy. Another important aspect of implementing gene therapy in the clinical arena is to be able to image the targeting of the therapeutics to the tumors, treatment effectiveness and progression of disease. We have therefore reviewed the most exciting non-invasive, in vivo imaging techniques which can be used in combination with gene therapy to monitor therapeutic efficacy over time.

show abstract

Section: Dendritic Cellsmentioning

confidence: 95%

Section: Dendritic Cellsmentioning

confidence: 99%

Combining Cytotoxic and Immune-Mediated Gene Therapy to Treat Brain Tumors

Curtin

King

Candolfi

et al. 2005

CTMC

View full text Add to dashboard Cite

show abstract

“…Since many tumors lack appropriate costimulatory ligands for T cell activation (5), numerous studies have aimed at introducing costimulatory molecules into tumor cells via gene transfer, including the CD28 ligands CD80 (B7-1) and CD86 (B7-2). Using established tumor cell lines which were modified by electroporation (30,31) or by recombinant viral vector transfection (32)(33)(34) to express the costimulatory molecules, this strategy often resulted in impressive tumor regression rates and antitumor immunity in various murine tumor models. A clinical application of this approach, however, is generally impeded by technical hurdles and low transfection efficiencies.…”

Section: Discussionmentioning

confidence: 99%

An effective tumor vaccine optimized for costimulation via bispecific and trispecific fusion proteins

Aigner

Janke²,

Lulei³

et al. 2008

Int J Oncol

View full text Add to dashboard Cite

Abstract. T cell costimulation has great therapeutic potential if it can be optimized and controlled. To achieve this, we engineered T cell-activating fusion proteins and immunocytokines that specifically attach to viral antigens of a virusinfected tumor vaccine. We employed the avian Newcastle Disease Virus because this agent is highly efficient for human tumor cell infection, and leads to introduction of viral hemagglutinin-neuraminidase (HN) molecules at the tumor cell surface. Here, we demonstrated the strong potentiation of the T cell stimulatory activity of such a vaccine upon attachment of bispecific or trispecific fusion proteins which bind with one arm to viral HN molecules of the vaccine, and with the other arm either to CD3 (signal 1), to CD28 (costimulatory signal 2a), or to interleukin-2 receptor (costimulatory signal 2b) on T cells. A vaccine with a combination of all three signals triggered the strongest activation of naïve human T cells, thereby inducing the most durable bystander antitumor activity in vitro. Adoptive transfer of such polyclonally activated cells into immunodeficient mice bearing human breast carcinoma caused tumor regression. Furthermore, tumor-reactive memory T cells from draining lymph nodes of carcinoma patients could be efficiently reactivated in a short-term ELISpot assay using an autologous tumor vaccine with optimized signals 1 and 2, but not with a similarly modified vaccine from an unrelated tumor cell line. Our data describe new bioactive molecules which in combination with an established virus-modified tumor vaccine greatly augments the antitumor activity of T cells from healthy donors and cancer patients. IntroductionThe strength of T cell stimulation is determined by numerous parameters including i) the concentration of major histocompatibility complex-restricted antigen on the surface of antigen-presenting cells (APCs) such as dendritic cells (DCs) and its affinity for the T cell receptor (TCR; determining the rate of TCR triggering) (1,2), ii) the presence or absence of costimulation (regulating the extent of signal amplification) (3,4), such as costimulation via CD28 which is the most prominent costimulatory receptor on T cells (5,6), and iii) the duration of the interactions between T cells and DCs (setting the duration of the signalling process) (7,8). A low-strength stimulation which may occur with tumor cells can have a negative effect leading to T cell unresponsiveness (anergy) (9), or apoptosis (10,11). However, CD28 engagement drives interleukin-2 (IL-2) production (12,13), a cytokine pivotal for T cell growth, survival and cytotoxicity (14).We have already reported on three recombinant, monomeric single chain Fv (scFv) fusion proteins (15-17). These specially designed molecules provide T cell activation signals by interacting either with the TCR-associated CD3 complex [signal 1, mediated by the bispecific (bs) fusion protein bsHN-CD3], or with the costimulatory molecule CD28 (signal 2a, mediated by bsHN-CD28), or with the IL-2 receptor (signal 2b, mediate...

show abstract

“…Immunoprotection gene therapy may enhance host immunity against regrowth of leukemia cells through the administration of gene-modified autologous leukemia cells. Recent mouse studies, mainly using solid tumor models, have shown that the transduction of cDNAs encoding cytokines [4][5][6][7] or costimulatory molecules [8][9][10] into tumor cells helped to decrease the tumorigenicity of the cells or endowed them with in vivo vaccination efficacy. Since differences in immunological properties between hematopoietic malignant cells and solid tumor cells were suggested, 11 it may be worthwhile to test the propriety of adopting immuno/gene therapeutic approaches to leukemia therapy.…”

Section: Introductionmentioning

confidence: 99%

Gene transfer of pro-IL-18 and IL-1β converting enzyme cDNA induces potent antitumor effects in L1210 cells

Zhang

et al. 2004

Leukemia

View full text Add to dashboard Cite

B7.1 immunogene therapy effectively activates CD4+ tumor-infiltrating lymphocytes in the central nervous system in comparison with B7.2 gene therapy

Cited by 8 publications

References 0 publications

Combining Cytotoxic and Immune-Mediated Gene Therapy to Treat Brain Tumors

Combining Cytotoxic and Immune-Mediated Gene Therapy to Treat Brain Tumors

An effective tumor vaccine optimized for costimulation via bispecific and trispecific fusion proteins

Gene transfer of pro-IL-18 and IL-1β converting enzyme cDNA induces potent antitumor effects in L1210 cells

Contact Info

Product

Resources

About