Dataset Information

Long-term survival and outcome of patients originally given Mycobacterium vaccae for metastatic malignant melanoma.

ABSTRACT: BACKGROUND:The long-term prognosis of patients with stage IV AJCC melanoma is extremely poor. We have previously published short-term clinical outcome and immunological responses to a heat killed Mycobacterium vaccae-based vaccine. RESULTS:In this study we report on a better than expected long-term survival (3-y DSS 29·6%, 5-y, and 7-y DSS both 23·9%) relative to historical controls in the patients who received the vaccine in these trials, published in 1999 and 2003. Although the complete or partial response was only 10%, it was the remarkable response to other interventions upon relapse, such as surgery and radiotherapy followed by stable disease that was previously unexpected. METHODS:We reviewed the outcome of 72 patients who were treated with M. vaccae for metastatic melanoma between January 1996 and July 2004. CONCLUSION:Given this remarkable outcome in stage IV metastatic melanoma and its lack of toxicity we propose that this would make a promising candidate for randomized trials for stage III fully resected melanoma.

SUBMITTER: Cananzi FC

PROVIDER: S-EPMC3981853 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Long-term survival and outcome of patients originally given Mycobacterium vaccae for metastatic malignant melanoma.

Cananzi Ferdinando C M FC Mudan Satvinder S Dunne Mary M Belonwu Nneka N Dalgleish Angus G AG

Human vaccines & immunotherapeutics 20130709 11

<h4>Background</h4>The long-term prognosis of patients with stage IV AJCC melanoma is extremely poor. We have previously published short-term clinical outcome and immunological responses to a heat killed Mycobacterium vaccae-based vaccine.<h4>Results</h4>In this study we report on a better than expected long-term survival (3-y DSS 29·6%, 5-y, and 7-y DSS both 23·9%) relative to historical controls in the patients who received the vaccine in these trials, published in 1999 and 2003. Although the ...[more]

PMID: 23863507

Similar Datasets

Project description:Melanoma treatment has been revolutionized over the past decade. Long-term results with immuno-oncology (I-O) agents and targeted therapies are providing evidence of durable survival for a substantial number of patients. These results have prompted consideration of how best to define long-term benefit and cure. Now more than ever, oncologists should be aware of the long-term outcomes demonstrated with these newer agents and their relevance to treatment decision-making. As the first tumor type for which I-O agents were approved, melanoma has served as a model for other diseases. Accordingly, discussions regarding the value and impact of long-term survival data in patients with melanoma may be relevant in the future to other tumor types. Current findings indicate that, depending on the treatment, over 50% of patients with melanoma may gain durable survival benefit. The best survival outcomes are generally observed in patients with favorable prognostic factors, particularly normal baseline lactate dehydrogenase and/or a low volume of disease. Survival curves from melanoma clinical studies show a plateau at 3 to 4 years, suggesting that patients who are alive at the 3-year landmark (especially in cases in which treatment had been stopped) will likely experience prolonged cancer remission. Quality-of-life and mixture-cure modeling data, as well as metrics such as treatment-free survival, are helping to define the value of this long-term survival. In this review, we describe the current treatment landscape for melanoma and discuss the long-term survival data with immunotherapies and targeted therapies, discussing how to best evaluate the value of long-term survival. We propose that some patients might be considered functionally cured if they have responded to treatment and remained treatment-free for at least 2 years without disease progression. Finally, we consider that, while there have been major advances in the treatment of melanoma in the past decade, there remains a need to improve outcomes for the patients with melanoma who do not experience durable survival.

Project description:Tuberculosis (TB) is one of the leading causes of death worldwide, especially in developing countries. Neonatal BCG vaccination occurs in various regions, but the level of protection varies in different populations. Recently, Mycobacterium vaccae is found to be an immunomodulating therapeutic agent that could confer a significant level of protection against TB. It is the only vaccine in a phase III trial from WHO to assess its efficacy and safety in preventing TB disease in people with latent TB infection. However, the mechanism of immunotherapy of M. vaccae remains poorly understood. In this study, the full genome of M. vaccae was obtained by next-generation sequencing technology, and a proteogenomic approach was successfully applied to further perform genome annotation using high resolution and high accuracy MS data. A total of 3,387 proteins (22,508 unique peptides) were identified, and 581 proteins annotated as hypothetical proteins in the genome database were confirmed. Furthermore, 38 novel protein products not annotated at the genome level were detected and validated. Additionally, the translational start sites of 445 proteins were confirmed, and 98 proteins were validated through extension of their translational start sites based on N terminus-derived peptides. The physicochemical characteristics of the identified proteins were determined. Thirty-five immunogenic proteins of M. vaccae were identified by immunoproteomic analysis, and 20 of them were selected to be expressed and validated by Western blot for immunoreactivity to serum from patients infected with M. tuberculosis The results revealed that eight of them showed strong specific reactive signals on the immunoblots. Furthermore, cellular immune response was further examined and one protein displayed a higher cellular immune level in pulmonary TB patients. Twelve identified immunogenic proteins have orthologous in H37Rv and BCG. This is the first study to obtain the full genome and annotation of M. vaccae using a proteogenomic approach, and some immunogenic proteins that were validated by immunoproteomic analysis could contribute to the understanding of the mechanism of M. vaccae immunotherapy.

Dataset Information

Long-term survival and outcome of patients originally given Mycobacterium vaccae for metastatic malignant melanoma.

Publications

Long-term survival and outcome of patients originally given Mycobacterium vaccae for metastatic malignant melanoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets