Manipulation of costimulatory signals to enhance antitumor T-cell responses

Allison, James P.; Hurwitz, Arthur A.; Leach, Dana R.

doi:10.1016/0952-7915(95)80077-8

Cited by 158 publications

(81 citation statements)

References 30 publications

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“…The fibroblast cell lines were selected because they expressed syngeneic (H-2 b ) or allogeneic (H-2 k ) MHC class I determinants, along with the costimulatory molecule B7.1, enabling them to act as antigen presenting cells. 32,33 Before DNA transfer, the fibroblasts were modified to secrete IL-2, to further augment their immunogenic properties. 34 The immunogenic properties of the transfected cells were then compared in C57BL/6 mice with melanoma.…”

Section: Fibroblasts Survived Significantly Longer Than Mice In Variomentioning

confidence: 99%

An optimum anti-melanoma response in mice immunized with fibroblasts transfected with DNA from mouse melanoma cells requires the expression of both syngeneic and allogeneic MHC-determinants

2002

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Section: Fibroblasts Survived Significantly Longer Than Mice In Variomentioning

confidence: 99%

An optimum anti-melanoma response in mice immunized with fibroblasts transfected with DNA from mouse melanoma cells requires the expression of both syngeneic and allogeneic MHC-determinants

2002

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“…4,5 Intensive research efforts are currently being directed at defining therapeutic strategies that bypass these inherent limitations in the induction of antitumour immunity. These strategies include the expression of costimulatory molecules on tumour cells 6 and ex vivo manipulation of APC such that tumour antigens are presented by MHC class-I molecules. Among professional APC, which include macrophages, B-lymphocytes and dendritic cells (DC), DC are the most potent stimulators of antigen-specific T-lymphocyte responses.…”

Section: Introductionmentioning

confidence: 99%

Human PBMC-derived dendritic cells transduced with an adenovirus vector induce cytotoxic T-lymphocyte responses against a vector-encoded antigen in vitro

et al. 1999

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Dendritic cells (DC) are among the most potent antigentor encoding bacterial ␤-galactosidase (␤-gal) under the presenting cells known and play an important role in the transcriptional control of a CMV promoter was used to initiation of antigen-specific T-lymphocyte responses. Sevtransduce DC at multiplicities of infection (MOI) up to 1000. eral recent studies have demonstrated that DC expressing While high MOI were required to achieve efficient transducvector-encoded tumour-associated antigens can induce tion there was no significant effect on DC morphology, protective and therapeutic immunity in murine cancer modimmunophenotype or potency in allogeneic lymphocyte els. In the current study we set out to examine in vitro the proliferation assays. Furthermore, transduced DC-induced utility of adenovirus vectors in the transduction of human antigen-specific CTL activity against adenoviral proteins DC for the induction of antigen-specific T-lymphocyte and more significantly, the vector-encoded antigen ␤-gal. responses against a defined vector-encoded antigen. DC These data clearly demonstrate the potential of adenovirus were derived from the adherent fraction of PBMC by culvectors in anticancer DC vaccine strategies and provide ture in defined medium containing GM-CSF and IL-4. A an important link between existing animal data and human replication-defective E1/E3-deleted type 5 adenovirus vecclinical application.

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“…All these data suggest priming of melan-A-specific CTL by malignant melanoma is weak. This should perhaps not be unduly surprising, because tumor cells usually lack costimulatory molecules (37,38), and tumor Ags have no direct route into the MHC class I pathway of professional APCs.…”

Section: Priming Of Melan-a-specific Ctl Precursors Is Often Weak In mentioning

confidence: 99%

A Shift in the Phenotype of Melan-A-Specific CTL Identifies Melanoma Patients with an Active Tumor-Specific Immune Response

Dunbar¹,

Smith²,

Chao

et al. 2000

The Journal of Immunology

123

117

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In a significant proportion of melanoma patients, CTL specific for the melan-A26/7–35 epitope can be detected in peripheral blood using HLA-A2/peptide tetramers. However, the functional capacity of these CTL has been controversial, since although they prove to be effective killers after in vitro expansion, in some patients they have blunted activation responses ex vivo. We used phenotypic markers to characterize melan-A tetramer+ cells in both normal individuals and melanoma patients, and correlated these markers with ex vivo assays of CTL function. Melanoma patients with detectable melan-A tetramer+ cells in peripheral blood fell into two groups. Seven of thirteen patients had a CCR7+ CD45R0− CD45RA+ phenotype, the same as that found in some healthy controls, and this phenotype was associated with a lack of response to melan-A peptide ex vivo. In the remaining six patients, melan-A tetramer+ cells were shifted toward a CCR7− CD45R0+ CD45RA− phenotype, and responses to melan-A peptide could be readily demonstrated ex vivo. When lymph nodes infiltrated by melan-A-expressing melanoma cells were examined, a similar dichotomy emerged. These findings demonstrate that activation of melan-A-specific CTL occurs in only some patients with malignant melanoma, and that only patients with such active immune responses are capable of responding to Ag in ex vivo assays.

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Manipulation of costimulatory signals to enhance antitumor T-cell responses

Cited by 158 publications

References 30 publications

An optimum anti-melanoma response in mice immunized with fibroblasts transfected with DNA from mouse melanoma cells requires the expression of both syngeneic and allogeneic MHC-determinants

An optimum anti-melanoma response in mice immunized with fibroblasts transfected with DNA from mouse melanoma cells requires the expression of both syngeneic and allogeneic MHC-determinants

Human PBMC-derived dendritic cells transduced with an adenovirus vector induce cytotoxic T-lymphocyte responses against a vector-encoded antigen in vitro

A Shift in the Phenotype of Melan-A-Specific CTL Identifies Melanoma Patients with an Active Tumor-Specific Immune Response

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