Immunotherapy of malignant melanoma

Kadison, Alan S.; Morton, Donald L.

doi:10.1016/s0039-6109(02)00162-7

Cited by 28 publications

(21 citation statements)

References 120 publications

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“…*Po0.05. DTIC therapy, the use of tumor lysates and whole tumor vaccines, tumor-derived peptides, DC-based vaccination protocols, and adoptive transfer of tumor-specific T cells (Kadison and Morton, 2003). These approaches have so far obtained little success in the clinic, are complex and laborintensive, thereby limiting their potential for widespread use.…”

Section: Discussionmentioning

confidence: 99%

Dacarbazine-Mediated Upregulation of NKG2D Ligands on Tumor Cells Activates NK and CD8 T Cells and Restrains Melanoma Growth

Hervieu

Rébé

Végran

et al. 2013

Journal of Investigative Dermatology

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Dacarbazine (DTIC) is a cytotoxic drug widely used for melanoma treatment. However, the putative contribution of anticancer immune responses in the efficacy of DTIC has not been evaluated. By testing how DTIC affects host immune responses to cancer in a mouse model of melanoma, we unexpectedly found that both natural killer (NK) and CD8(+) T cells were indispensable for DTIC therapeutic effect. Although DTIC did not directly affect immune cells, it triggered the upregulation of NKG2D ligands on tumor cells, leading to NK cell activation and IFNγ secretion in mice and humans. NK cell-derived IFNγ subsequently favored upregulation of major histocompatibility complex class I molecules on tumor cells, rendering them sensitive to cytotoxic CD8(+) T cells. Accordingly, DTIC markedly enhanced cytotoxic T lymphocyte antigen 4 inhibition efficacy in vivo in an NK-dependent manner. These results underscore the immunogenic properties of DTIC and provide a rationale to combine DTIC with immunotherapeutic agents that relieve immunosuppression in vivo.

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Section: Discussionmentioning

confidence: 99%

Dacarbazine-Mediated Upregulation of NKG2D Ligands on Tumor Cells Activates NK and CD8 T Cells and Restrains Melanoma Growth

Hervieu

Rébé

Végran

et al. 2013

Journal of Investigative Dermatology

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“…The present dramatic rise in melanoma incidence necessitates new and effective treatment strategies [1][2][3][4][5][6][7][8][9][10]. Gene therapy is an emerging technology with great promise as an effective treatment for a wide range of diseases.…”

Section: Discussionmentioning

confidence: 99%

“…At present, therapeutic strategies include polychemotherapy or chemoimmunotherapy; however, many patients with melanoma are resistant to these available therapeutics. Development of new cancer therapies is focused on stimulation of the immune system with vaccines that deliver relevant antigens and immunologic molecules [5][6][7][8][9][10]. Unfortunately, these therapies have yet to demonstrate survival benefits.…”

Section: Introductionmentioning

confidence: 99%

RNAi silencing of the WT1 gene inhibits cell proliferation and induces apoptosis in the B16F10 murine melanoma cell line

et al. 2007

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The Wilms' tumor protein 1 (WT1) is essential for tumor cell proliferation and is highly expressed in various hematological and solid malignancies including human malignant melanoma. We investigated whether WT1 expression is essential for growth in the B16F10 murine melanoma cell line. Toward this end, we examined WT1 protein expression and WT1 isoforms (17AA+/17AA-, KTS+/KTS-) in this cell line. WT1 was silenced by two RNA interference constructs, designated WT1-1 and WT1-2. RNA interference-mediated reduction of WT1 protein expression significantly inhibited B16F10 cell viability. Loss of WT1 also increased caspase-3 and poly-ADP-ribose polymerase activation, as well as apoptotic body formation, chromatin condensation, and DNA fragmentation. Together, these findings implicate decreased WT1 protein levels in the induction of apoptosis. These results imply that WT1 plays a distinct role in B16F10 melanoma growth.

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“…6,7 One of the most studied methods of tumor immunotherapy involves the in vitro manipulation of DCs. In this experiment, we investigated the possibility of using human DCs pulsed with our laboratory's polyvalent melanoma vaccine (DC-IL-2VMO) for the possible treatment of Stage III melanoma.…”

Section: Resultsmentioning

confidence: 99%

Expression of melanoma-associated antigens in human dendritic cells pulsed with an interleukin-2 gene encoded vaccinia melanoma oncolysate (rIL-2VMO)

Aydin

Jack²,

Montenegro³

et al. 2006

Cancer Biology & Therapy

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[Cancer Biology & Therapy 5:12, 1654-1657, December 2006 ABstrACtDendritic cells (DCs) possess the unique abilities to initiate a primary immune response and to present antigens to naïve T lymphocytes. Recently, there has been a rapidly growing interest in the use of DCs in active specific immunotherapy (ASI) for the treatment of patients with cancer. In the present study, we determined the ability of DCs to express Melanoma-Associated Antigens (MAAs) from a polyvalent Melanoma Vaccine (DC-MelVac; Patent #11221/5) developed in our facility. The vaccine consists of a recombinant IL-2 gene-encoded vaccinia melanoma oncolysate (rIL-2VMO) derived from an established human melanoma cell line. Our results show that r-IL2VMO-pulsed DCs express MAAs presented by the Mel-2 melanoma cell line oncolysate used in this study. We believe that these promising results will prove useful as an active specific immunotherapeutic agent for patients with Stage III melanoma.

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Immunotherapy of malignant melanoma

Cited by 28 publications

References 120 publications

Dacarbazine-Mediated Upregulation of NKG2D Ligands on Tumor Cells Activates NK and CD8 T Cells and Restrains Melanoma Growth

Dacarbazine-Mediated Upregulation of NKG2D Ligands on Tumor Cells Activates NK and CD8 T Cells and Restrains Melanoma Growth

RNAi silencing of the WT1 gene inhibits cell proliferation and induces apoptosis in the B16F10 murine melanoma cell line

Expression of melanoma-associated antigens in human dendritic cells pulsed with an interleukin-2 gene encoded vaccinia melanoma oncolysate (rIL-2VMO)

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