Melanoma antigen-specific effector T cell cytokine secretion patterns in patients treated with ipilimumab.

Background: In a previously reported study, patients with regionally advanced melanoma were treated with neoadjuvant ipilimumab (ipi) (Tarhini in PLoS ONE 9(2): e87705, 3). Significant changes in circulating myeloid derived suppressor cells (MDSC), regulatory T cells (Treg) and peptide specific type I CD4 and CD8 T cells were noted at week 6 that correlated with clinical outcome. Characterization of antigen-specific effector T cell secreted cytokines may shed insights into ipi associated T cell activation and function.

Phenotypic and functional testing of circulating regulatory T cells in advanced melanoma patients treated with neoadjuvant ipilimumab.

Background: We have previously investigated neoadjuvant ipilimumab (ipi) for patients with locally/regionally advanced melanoma. That initial assessment of peripheral blood mononuclear cells (PBMC) showed a significant increase in shared tumor associated antigen specific CD4(+) and CD8(+) T cell activation. We also observed a transient increase in circulating T regulatory cells (Treg) with a parallel increase in total CD4(+) T cells, as well as a significant decrease in circulating myeloid derived suppressor cells (MDSC).

Baseline circulating IL-17 predicts toxicity while TGF-β1 and IL-10 are prognostic of relapse in ipilimumab neoadjuvant therapy of melanoma.

Background: We evaluated candidate circulating serum cytokines, chemokines and growth factors in patients with locally/regionally advanced melanoma receiving neoadjuvant ipilimumab with toxicity and clinical outcome.

Methods: Patients were treated with ipilimumab (10 mg/kg IV every 3 weeks, 2 doses) before and after surgery. xMAP multiplex serum testing for 36 functionally selected cytokines and chemokines was performed at baseline and at six weeks (following ipilimumab).

Immunotherapy of Melanoma.

The host antitumor immune response in patients with advanced melanoma is compromised with a bias towards tumor immune tolerance and a tumor microenvironment that facilitates disease survival and progression. Overcoming tumor-induced immune suppression has been one of the most significant advances in cancer therapy, making a cure an ever closer and achievable goal. Immunotherapeutic strategies in melanoma have been built upon the immunomodulatory qualities and the early successes of interferon-α in the melanoma adjuvant setting and interleukin-2 in the treatment of inoperable advanced melanoma.

Melanoma adjuvant therapy.

Adjuvant therapy targets melanoma micrometastases in patients with surgically resected disease that carry a high risk of death from melanoma recurrence. In this setting, adjuvant therapy provides the greatest opportunity for cure before progression into advanced inoperable stages. In randomized clinical trials, interferon-alfa has been shown to have a significant impact on relapse-free survival and, at high dosage, on overall survival compared with observation (E1684) and the GMK vaccine (E1694).

Phase I trial of carboplatin and etoposide in combination with panobinostat in patients with lung cancer.

Unlabelled: A phase I trial consisting of panobinostat (a HDAC inhibitor), carboplatin and etoposide was conducted in patients with lung cancer.

Patients And Methods: Patients received carboplatin AUC5 on day 1 and etoposide 100 mg/m(2) on days 1, 2 and 3, every 21 days. Concurrent oral panobinostat was given 3 times weekly on a 2-weeks-on and 1-week-off schedule during the 4-6 cycles of chemotherapy and then continued as maintenance therapy.