Abstract
Treatment of metastatic melanoma is a challenge for clinicians as most agents have failed to demonstrate improved survival in phase III trials. Despite the immunogenicity of this tumor entity, different immunological interventions including cytokine therapy, vaccination, biochemotherapy or allogeneic hematopoietic cell transplantation did not lead to a satisfactory response. However, continuous investigation on the immune mediated rejection of melanoma cells has led to the development of effective antibodies blocking cytotoxic T-lymphocyte antigen-4 (CTLA-4), a critical negative regulator of the antitumor T-cell response. Based on data from rodent models, the anti-CTLA-4 antibody ipilimumab was developed into clinical studies where it had encouraging activity in advanced melanoma with unusual response patterns. As in most immunostimulatory therapies, acute toxicities were severe and clearly mechanism-related. Although some patients developed signs of autoimmunity, the toxicities were overall manageable and mostly reversible.
This review summarizes different immunotherapeutical approaches against melanoma that have been applied in the past and focuses on CTLA-4 blockade with respect to its mechanism, clinical effectiveness and immunological side effects.
Keywords: Allogeneic transplantation, CTLA-4, immunotherapy, malignant melanoma
Current Stem Cell Research & Therapy
Title:Immunotherapy for Malignant Melanoma Robert
Volume: 7 Issue: 3
Author(s): Robert Zeiser, Marc Schnitzler, Hana Andrlová, Tina Hellige and Frank Meiss
Affiliation:
Keywords: Allogeneic transplantation, CTLA-4, immunotherapy, malignant melanoma
Abstract: Treatment of metastatic melanoma is a challenge for clinicians as most agents have failed to demonstrate improved survival in phase III trials. Despite the immunogenicity of this tumor entity, different immunological interventions including cytokine therapy, vaccination, biochemotherapy or allogeneic hematopoietic cell transplantation did not lead to a satisfactory response. However, continuous investigation on the immune mediated rejection of melanoma cells has led to the development of effective antibodies blocking cytotoxic T-lymphocyte antigen-4 (CTLA-4), a critical negative regulator of the antitumor T-cell response. Based on data from rodent models, the anti-CTLA-4 antibody ipilimumab was developed into clinical studies where it had encouraging activity in advanced melanoma with unusual response patterns. As in most immunostimulatory therapies, acute toxicities were severe and clearly mechanism-related. Although some patients developed signs of autoimmunity, the toxicities were overall manageable and mostly reversible.
This review summarizes different immunotherapeutical approaches against melanoma that have been applied in the past and focuses on CTLA-4 blockade with respect to its mechanism, clinical effectiveness and immunological side effects.
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Cite this article as:
Zeiser Robert, Schnitzler Marc, Andrlová Hana, Hellige Tina and Meiss Frank, Immunotherapy for Malignant Melanoma Robert, Current Stem Cell Research & Therapy 2012; 7 (3) . https://dx.doi.org/10.2174/157488812799859883
DOI https://dx.doi.org/10.2174/157488812799859883 |
Print ISSN 1574-888X |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3946 |
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