Antibody therapies for melanoma: New and emerging opportunities to activate immunity (Review) (original) (raw)
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Antibody-Based Immunotherapy: Alternative Approaches for the Treatment of Metastatic Melanoma
Biomedicines, 2020
Melanoma is the least common form of skin cancer and is associated with the highest mortality. Where melanoma is mostly unresponsive to conventional therapies (e.g., chemotherapy), BRAF inhibitor treatment has shown improved therapeutic outcomes. Photodynamic therapy (PDT) relies on a light-activated compound to produce death-inducing amounts of reactive oxygen species (ROS). Their capacity to selectively accumulate in tumor cells has been confirmed in melanoma treatment with some encouraging results. However, this treatment approach has not reached clinical fruition for melanoma due to major limitations associated with the development of resistance and subsequent side effects. These adverse effects might be bypassed by immunotherapy in the form of antibody–drug conjugates (ADCs) relying on the ability of monoclonal antibodies (mAbs) to target specific tumor-associated antigens (TAAs) and to be used as carriers to specifically deliver cytotoxic warheads into corresponding tumor cell...
Expert Review of Dermatology, 2012
Background: Immunotherapy for cancers is based on the principle that the host's immune system is capable of generating immune responses against tumor cells. Currently available treatments for melanoma patients are limited by poor response rates. Interferon-α has been approved for adjuvant treatment of stage III melanoma with improved survival. New and more innovative approaches with improved efficacy are needed. Methods: We reviewed the various new approaches and strategies for immunotherapy for the treatment of melanoma. Results: Immunotherapy for melanoma includes a number of different strategies with vaccines utilizing whole cell tumors, peptides, cytokine-mediated dendritic cells, DNA and RNA, and antibodies. Conclusions: A variety of approaches can be used to enhance immune reactivity in patients with melanoma. Preclinical studies and initial clinical trials have shown promising results. Additional clinical trials are currently ongoing to evaluate the clinical efficacy and the associated toxicities of these novel treatment strategies. Immunotherapy holds promise as an innovative and more effective approach for treatment of melanoma.
Mount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine, 2010
Melanoma immunotherapy has been an area of intense research for decades, and this work is now yielding more tangible results for patients. Work has focused on 4 main areas: cytokine therapy, administration of immune-modulating antibodies, adoptive T-cell therapy, and vaccines. Cytokine therapy is an established treatment for advanced melanoma, and immune-modulating antibodies have recently emerged as an exciting new area of drug development with efficacy now established in a phase III trial. Adoptive T-cell therapy provides the proof of principle that T cells can attack and eliminate tumors. It has been challenging, however, to adapt this treatment for widespread use. Vaccines have generally yielded poor results, but intratumor pathogen-based strategies have shown encouraging results in recent trials, perhaps due to stronger immune stimulation. A review of the field of melanoma immunotherapy is provided here, with emphasis on those agents that have reached clinical testing. Novel strategies to induce the immune system to attack melanomas are reviewed. In the future, it is envisioned that immunotherapy will have further application in combination with cytotoxic and targeted therapies. Mt Sinai J Med 77:620-642, 2010. 2010 Mount Sinai School of Medicine
Advances in Immunotherapy for Melanoma: A Comprehensive Review
Mediators of inflammation, 2017
Melanomas are tumors originating from melanocytes and tend to show early metastasis secondary to the loss of cellular adhesion in the primary tumor, resulting in high mortality rates. Cancer-specific active immunotherapy is an experimental form of treatment that stimulates the immune system to recognize antigens on the surface of cancer cells. Current experimental approaches in immunotherapy include vaccines, biochemotherapy, and the transfer of adoptive T cells and dendritic cells. Several types of vaccines, including peptide, viral, and dendritic cell vaccines, are currently under investigation for the treatment of melanoma. These treatments have the same goal as drugs that are already used to stimulate the proliferation of T lymphocytes in order to destroy tumor cells; however, immunotherapies aim to selectively attack the tumor cells of each patient. In this comprehensive review, we describe recent advancements in the development of immunotherapies for melanoma, with a specific ...
Current immunotherapy of melanoma
Clinical and Applied Immunology Reviews, 2005
The immunotherapy of patients with metastatic melanoma is currently at a crossroads. Indeed, recent results from vaccine strategies worldwide have revealed a strikingly low overall response rate in patients with stage IV melanoma. Although disappointing, we have gained valuable insight and knowledge about how vaccines interact with the host immune response and to melanoma. However, although an immunological response to therapy is often reported from various clinical trials, it does not contribute to a patient's long term survival. It has been proven time and again that an immunological response to therapy does not necessarily translate into a meaningful clinical response. This frustrating dichotomy of response continues to vex investigators, providing a glaring example of our poor understanding of the immunologic response to cancer. Thus, we remain at the crossroads of understanding and treatment. On the one hand, we have dramatically advanced the field of tumor immunology/ immunotherapy over the last 20 years. On the other hand, we have made little headway in truly developing effective treatment options for patients with stage IV disease. We must realize our previous shortcomings and failures in order to learn from them and develop improved therapies. The future of immunotherapy remains a bright ray of hope for everyone, with the road to success paved with the previous hard work of thousands of clinicians and researchers everywhere. Towards this end, this review hopes to provide the reader with the current state of affairs for the immunotherapy of melanoma as well as a primer of where we might be heading in the future. ą
Immunotherapy of advanced or metastatic melanoma
Clinical advances in hematology & oncology : H&O, 2007
Melanoma is often evaluated for the development of anticancer immunotherapeutics. Fascinating immune and clinical responses in small numbers of patients have prompted various approaches, ranging from nonspecific immune stimulation to therapies that target specific antigens. Unfortunately, these immune therapies have often shown limited success and objective responses have been seen in only a modest subset of patients. The challenge has been to identify factors that can lead to more consistent clinical benefit and to develop strategies to overcome the obstacles to successful antitumor immunity. Over the last 15 years many immune targets have been identified in cancers and the mechanisms underpinning clinical responses have become better understood. Furthermore, new ways to manipulate anticancer immunity are making it possible to overcome cancer immune evasion and subversion. New therapeutic strategies are resulting from these emerging insights into the relationship between melanoma a...
A New Era of Immunotherapy in Malignant Melanoma
2017
Even though melanoma skin cancer is less common than non-melanoma skin cancers (squamous cell carcinoma and basal cell carcinoma), still its mortality rate is relatively higher. Early diagnosis is the mainstay option to improve the disease outcome as early-stage melanoma made a favorable prognosis with surgical intervention. In contrast, advanced stage melanoma which is disseminated to distant sites through the lymphatics is associated with poor prognosis. Earlier traditional treatment modalities like interleukin 2 and non-specific anti-neoplastic agents are ineffective in improving the survival outcome and also the side-effects of these drugs have always been a treatment burden. However, recent understanding of immunotherapeutic approach against melanoma cancer has revolutionized the whole treatment scenario. Various adaptations of immunotherapies like targeted therapy, monoclonal antibodies, Toll-like receptors, T-cell therapy and oncolytic viral therapy has shown significant impr...
Immunotherapy of melanoma: efficacy and mode of action
Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG, 2016
Forty years of research have brought about the development of antibodies that induce effective antitumor immune responses through sustained activation of the immune system. These "immune checkpoint inhibitors" are directed against immune inhibitory molecules, such as cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1). Disruption of the PD-1/PD-L1 interaction improves the intermediate-term prognosis even in patients with advanced stage IV melanoma. One and a halfyears after treatment initiation, 30-60 % of these patients are still alive. While cancer immunotherapies usually do not eradicate metastases completely, they do cause a regression by 20-80 %. It is well established that the immune system is able to kill tumor cells, and this has also been demonstrated for immunotherapies. Preclinical data, however, has shown that anti-cancer immunity is not limited to killing cancer cells. Thus, through interferon gamma and tum...
NOVEL IMMUNOTHERAPIES FOR THE TREATMENT OF MELANOMA
Immunotherapies are achieving clinical success for the treatment of many cancers. However, it has taken a long time to exploit the potential of the immune system for the treatment of human cancers. We cannot forget that this has been the consequence of very extensive work in basic research in pre-clinical models and in human patients. Thus, it is rather hard to compile all of it while giving a comprehensive view on this subject. Here we have attempted to give an overall perspective in immunotherapy of melanoma. A brief overview on current therapies is provided, followed by adoptive cell therapies. Gene engineering strategies to improve these therapies are also explained, finishing with therapies based on interference with immune checkpoint pathways.
Advances in melanoma immunotherapy
2017
Melanoma is considered to be the most immunogenic malignant tumour. This fact is recognized for many years, and certain forms of immunotherapy have been used in melanoma therapy for a considerable time. Treatment options for patients with metastatic melanoma have changed dramatically in the past 5 years, with the FDA approval of eight new therapeutic agents (immunotherapies and targeted therapies). During this period, melanoma immunotherapy has transitioned from cytokine-based treatment to antibody-mediated blockade of the cytotoxic Tlymphocyteassociated antigen4 (CTLA4) and, recently, the programmed cell-death protein 1 (PD1) immune checkpoints. These changes in the treatment options have dramatically improved patient outcomes, with the median overall survival of patients with metastatic melanoma increasing from approximately 9 months before 2011 to at least 2 years, and probably longer. Various types of immunotherapy, like pembrolizumab, nivolumab, ipilimumab, combined therapy wit...