Therapeutic cancer vaccines

The last decade has seen a considerable improvement in the understanding of the biology of melanoma. Advances have come in the understanding of the importance of critical oncogenes and tumour suppressor genes, epigenetic phenomena, signalling pathways, drug resistance mechanisms, the pivotal role of the local immune system, and the importance of cell-cell and cell-matrix interactions. Many of these pathways and interactions include potentially 'drugable' targets. These developments have allowed the identification and/or design of a range of new, targeted therapies. Evaluation of these new drugs has brought a whole new series of challenges. These include identification of appropriate pre-clinical models, overcoming the redundancy in-built in complex biological systems, identification of appropriate molecular and clinical endpoints to show that the drug is hitting the target, how to combine treatments, and new toxicities. For the first time, there is the possibility of personalized treatment for melanoma patients, based on individual host and tumour characteristics. This paper discusses the range of new drugs and targets have been identified, the outcome of clinical trials, and the directions for future advances.

Systemic therapy for metastatic malignant melanoma – from deeply disappointing to bright future?

Seventy-four (74) patients with metastatic melanoma were treated with patient-specific vaccines derived from autologous tumor cell lines. Cryopreserved irradiated tumor cells were injected weekly for 3 weeks, then monthly for 5 months. At a median follow up >6 years, the median event-free survival (EFS) was 4.5 months, with 13 patients alive and progression free 6–12 years later. Median overall survival (OS) was 20.5 months, with 29% 5-year OS. Tumor response rate was 9% among the 35 patients with evaluable disease who received at least 3 injections. Better survival was observed for patients who had minimal rather than clinically evident metastatic disease at the time vaccine therapy was initiated (5-yr OS 47% vs. 13%; p 12 million cells p...

Patient-specific vaccines derived from autologous tumor cell lines as active specific immunotherapy: results of exploratory phase I/II trials in patients with metastatic melanoma.

Background: Heat shock proteins (HSP) play an essential role as molecular chaperones by assisting correct holding and folding in human cells. At the same time they present implications in tumor cell proliferation, differentiation, matrix invasion, angiogenesis, metastasis and cell death. They also possess the ability to present tumor molecules to the immune system and elicit an immune response. New agents targeting HSP, as anticancer treatment, are under clinical evaluation. Objective: The aim of this review is to explore the role of HSP90 inhibitors as anticancer agents as well as to evaluate the benefit from the use of autologous HSP vaccines in both the adjuvant setting and first-line treatment. Methods: The latest evidence regarding the use of geldanamycin analogues or newer water-soluble and synthetics molecules that inhibit the binding of HSP90 to client proteins was reviewed. Immunization using tumor-derived HSP in several cancer types was also evaluated. Conclusions: HSP90 inhibitors represent a p...

Heat shock protein inhibitors and vaccines as new agents in cancer treatment.

Background: Melanoma is a tumour that is usually resistant to systemic therapy. Since it has been considered to be a highly immunogenic tumour, it has become an excellent target for the active specific immunotherapy. Vaccine therapy represents a novel approach to the treatment of melanoma. Objective: To evaluate different vaccines tested in stage III and/or IV melanoma patients. Methods: Systematic review of the published evidence on vaccine therapy in melanoma. Results: Melanoma vaccines can be classified into six groups: whole-cell vaccines, dendritic cell vaccines, peptide vaccines, ganglioside vaccines, DNA vaccines and viral vectors. The main characteristics of these vaccines including their advantages and disadvantages and the results from conducted trials are presented. Clinical responses to melanoma vaccines are still poor and currently there is no melanoma vaccine with a proven efficacy. Conclusion: Vaccine therapy still remains an experimental therapy in patients with metastatic melanoma. Furthe...

The role of vaccine therapy in the treatment of melanoma.

8002 Background: Vitespen (Oncophage; formerly HSPPC-96) is an autologous, tumor-derived, heat shock protein (gp96)-peptide complex vaccine that has shown signals of clinical activity in patients (...

Autologous tumor-derived HSPPC-96 vs. physician’s choice (PC) in a randomized phase III trial in stage IV melanoma

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Autologous tumor-derived HSPPC-96 vs. physician’s choice (PC) in a randomized phase III trial in stage IV melanoma