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Vaccine immunotherapy and prognostic factors of success: where we are today?

Dréno, B.

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doi: 10.1097/01.cmr.0000382776.28935.2e
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In the strategies for the development of vaccination in melanoma (peptides, proteins, dendritic cells and clones), one of the main challenge in the future is to identify early prognostic biomarkers of response permitting to select good candidates tot this type of treatment. The main tracks can concern serum markers, tissue markers, gene signature or TReg.

In a general manner, at the clinical level, contrary to interferon or anti CTLA-4, if vitiligo have been reported with vaccination, no auto immune prognostic biomarker have been identified with vaccination. The alone prognostic marker reported are slow evolution of metastasis with low burden.

Concerning dendritic cells today, we have no tissue biomarker and very few data concerning serologic biomarkers. It has just been demonstrated that an increase in CD8+CD16(−) perforin+ T lymphocytes could be positive prognostic markers for patients’ response to DC vaccines.

For protein and peptides vaccination: with GM-CSF gene-transduced autologous tumour cells, it has been shown that there was a correlation between serum level of S-100 and clinical evolution of melanoma: In patients who acquired a status of no clinical evidence of disease after treatment, the S-100B concentration invariably decreased by more than 100%.

With the MAGE-3 protein, a gene signature was identified, with a potential to predict the benefit from MAGE-A3 ASCI therapy in patients in metastatic stages. Most of the genes identified in the GS are immune-related suggesting presence of a specific tumor-environment prior to ASCI treatment. Confirmation of these results is on going with a new trial in adjuvant situation with patient in stage III (macroscopic lymph nodes).

For T cell clones, the most interesting biomarkers (because of early detection) are the increased frequencies in antigen Melan-A specific T cells in blood following treatment by clone Melan-A. This anti-tumor response is associated with increased frequencies of Melan-A specific T cells in blood. This increase frequency is an early phenomenon, less than one month after treating the patient. Concerning tissue biomarker, the in situ production of TGF beta and IL-10 by tumour cells of lymph node metastasis has been shown associated with a worse prognostic (relapses and survival). Finally, Tumor-reactive T cells persisting in the peripheral blood and at the tumor site for prolonged times following clone injection may be a tissue marker for complete tumor regression.

In the future, the prognostic role of T Reg in tissue or serum for response to vaccination remains to be determined. Among the tools tetramers appears of particular interest.

© 2010 Lippincott Williams & Wilkins, Inc.