Dendritic Cell Vaccines for Melanoma: Past, Present and Future

Dillman, Robert O.; Nistor, Gabriel; Cornforth, Andrew N.

doi:10.2217/mmt-2016-0014

Cited by 25 publications

(27 citation statements)

References 114 publications

(93 reference statements)

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“…Well-characterized melanoma TAA have also been loaded onto DC, as summarized previously [14]. Most of these were small exploratory studies focusing on induction of immune response to the TAA being presented but only rare tumor responses were reported.…”

Section: Well-characterized Melanoma Tumor-associated Antigensmentioning

confidence: 99%

“…Most of these were small exploratory studies focusing on induction of immune response to the TAA being presented but only rare tumor responses were reported. Pooled data from nine published studies of autologous DC loaded with HLA-2-restricted peptides yielded an objective response rate of only 11/201 (5.5%) [14]. One randomized trial using this approach was conducted in patients with measurable metastatic melanoma, and it was published over 10 years ago [15].…”

Section: Well-characterized Melanoma Tumor-associated Antigensmentioning

confidence: 99%

“…Data pooled for three studies that used autologous DC loaded with TAA from allogeneic tumor cell lines had a response rate of 6/68 (8.8%) [14]. This approach has not been tested in randomized trials.…”

Section: Allogeneic Cell Linesmentioning

confidence: 99%

“…Toward this end, there now a number of approaches being tested that utilize whole tumor, mRNA from whole tumor and short-term autologous tumor cell lines, rather than going through the tedious process of trying to identify all relevant neoantigens. Several trials using these approaches were summarized previously [7][8]14].…”

Section: Allogeneic Cell Linesmentioning

confidence: 99%

“…Randomized trial of intralesional vaccine to optimize dendritic cell processing and presentation of tumor-associated antigen versus intravenous dacarbazine in patients with advanced melanoma. 1 antigens [14]. Rather than increasing exposure to TAA, the rationale for the Allovectin product was enhancement of DC processing of available TAA for presentation to T cells.…”

Section: Intralesional Injections As a Therapeutic Vaccinementioning

confidence: 99%

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An Update on the Relevance of Vaccine Research for the Treatment of Metastatic Melanoma

Dillman¹

2017

Melanoma Manag.

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Past & present r In the past decade, the introduction of effective signal transduction inhibitors and anticheckpoint antibodies has significantly improved the prognosis for patients with metastatic melanoma, but the majority of such patients still die within 5 years. r Vaccine approaches designed to induce immunity to well-characterized melanoma-associated antigens, or to antigens expressed on allogeneic tumor cell lines, have not resulted in approved agents. r Despite the limitations associated with the immunosuppressive tumor microenvironment, there now is one intralesional autologous vaccine that has received regulatory approval for patients who have primarily soft-tissue metastases. Future r There are still unmet needs that may be met by therapeutic vaccines. r Successful vaccines likely will be those that induce or enhance recognition of patient-specific autologous neoantigens that result from nonsynonymous mutations contained in autologous tumor cells.Signal transduction inhibitors and anticheckpoint antibodies have significantly improved survival for metastatic melanoma patients, but most still die within 5 years. Vaccine approaches to induce immunity to well-characterized melanoma-associated antigens, or to antigens expressed on allogeneic tumor cell lines, have not resulted in approved agents. Despite the limitations associated with the immunosuppressive tumor microenvironment, there now is one intralesional autologous vaccine approved for patients who have primarily soft-tissue metastases. There is continued interest in patient-specific vaccines, especially dendritic cell vaccines that utilize ex vivo loading of autologous antigen, thus bypassing certain in vivo immunosuppressive cells and cytokines. Because of their mechanism of action and limited toxicity, they are potentially synergistic or additive to other antimelanoma therapies. A recent commentary concluded that there is a potential role for therapeutic vaccines in cancer therapy despite the clinical success of immune checkpoint inhibitors [1]. A similar conclusion previously was made for metastatic melanoma, in which it was argued that there is a strong rationale for therapeutic anticancer vaccines against metastatic melanoma even though to date no antimelanoma vaccines had been proven to be effective, and the best chance for success rested on approaches leading to recognition of autologous tumor cell antigens (tumor-associated antigen [TAA]) [2]. Furthermore, the suggestion that therapeutic vaccine research was no longer relevant because of the success of new targeted therapies including BRAF/MEK and immune-checkpoint inhibitors was refuted. The following is an update regarding these issues.

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Section: Well-characterized Melanoma Tumor-associated Antigensmentioning

confidence: 99%

Section: Well-characterized Melanoma Tumor-associated Antigensmentioning

confidence: 99%

Section: Allogeneic Cell Linesmentioning

confidence: 99%

Section: Allogeneic Cell Linesmentioning

confidence: 99%

Section: Intralesional Injections As a Therapeutic Vaccinementioning

confidence: 99%

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An Update on the Relevance of Vaccine Research for the Treatment of Metastatic Melanoma

Dillman¹

2017

Melanoma Manag.

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Immune therapy of melanoma: Overview of therapeutic vaccines

Payandeh

Yarahmadi

Nariman‐Saleh‐Fam

et al. 2019

Journal Cellular Physiology

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Melanoma is the most serious type of skin cancer which develops from the occurrence of genetic mutations in the melanocytes. Based on the features of melanoma tumors such as location, genetic profile and stage, there are several therapeutic strategies including surgery, chemotherapy, and radiotherapy. However, because of the appearance resistance mechanisms, the efficiency of these treatments strategies may be reduced. It has been demonstrated that therapeutic monoclonal antibodies can improve the efficiency of melanoma therapies. Recently, several mAbs, such as nivolumab, pembrolizumab, and ipilimumab, were approved for the immunotherapy of melanoma. The antibodies inhibit immune checkpoint receptors such as CTL4 and pd‐1. Another therapeutic strategy for the treatment of melanoma is cancer vaccines, which improve clinical outcomes in patients. The combination therapy using antibodies and gene vaccine give us a new perspective in the treatment of melanoma patients. Herein, we present the recent progressions in the melanoma immunotherapy, especially dendritic cells mRNA vaccines by reviewing recent literature.

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