Dendritic cell vaccination for metastatic melanoma: a 14-year monoinstitutional experience

Abstract

Although immunomodulating antibodies are highly effective in metastatic melanoma, their toxicity, related to the activation of T lymphocytes, can be severe. Anticancer vaccines promote a fairly specific response and are very well tolerated, but their effectiveness has yet to be demonstrated. We have been treating patients with advanced melanoma with an autologous dendritic cell vaccine since 2001; to better characterize the safety and efficacy of our product, we designed a retrospective study on all of our patients treated with the vaccine to date. We retrospectively reviewed both case report forms of patients included in clinical trials and medical records of those treated within a compassionate use program. Response was assessed according to the Response Evaluation Criteria In Solid Tumors criteria and toxicity has been graded according to CTCAE 4.0. Although the response rate has been rather low, the median overall survival of 11.4 months and the 1-year survival rate of 46.9% are encouraging, especially considering the fact that data were obtained in a heavily pretreated population and only about one quarter of the patients had received ipilimumab and/or BRAF inhibitors. Multivariate analysis confirmed that the development of an immune response was significantly correlated with a better prognosis (hazard ratio 0.54; P=0.019). The adverse events observed were generally mild and self-limiting. Our analysis confirms the excellent tolerability of our vaccine, making it a potential candidate for combination therapies. As efficacy seems largely restricted to immunoresponsive patients, future strategies should aim to increase the number of these patients.

Randomized phase II trial of autologous dendritic cell vaccines versus autologous tumor cell vaccines in metastatic melanoma: 5-year follow up and additional analyses

“…Second, the mechanism of action for the anti-programmed death-1 (PD1) checkpoint inhibitors is blocking the suppression of an existing immune response, but many patients show no evidence of an existing immune response in their tumors [ 10 , 11 ]. Third, therapeutic vaccines have been associated with survival benefit in some patients [ 12 , 13 ]. Fourth, dendritic cell vaccines can induce or enhance immune responses to patient-specific neoantigens [ 14 ].…”

Optimized dendritic cell vaccination induces potent CD8 T cell responses and anti-tumor effects in transgenic mouse melanoma models

“…We attempted to improve the presentation of shared melanoma-associated antigens (MAA) by dendritic cell (DC)-based immunotherapy since the clinical impact of such immunotherapy has been limited so far. 9 Efficient major histocompatibility complex (MHC)-peptide expression on DC and their activation determines the degree and quality of the T cell response. DCbased immunotherapies require improvements regarding (i) the origin and polarization of DC, (ii) the maturation stimuli by using better adjuvants, and (iii) the type and form of antigens to be loaded on DC.…”

Rhabdomyolysis during high dose interleukin-2 treatment of metastatic melanoma after sequential immunotherapies: a case report

“…An alternative immunotherapeutic option includes talimogene laherparepvec, (T-VEC), an oncolytic virus that mediates local and systemic antitumor activity by direct cancer cell lysis and an “in situ vaccine” effect [ 17 ]. Investigational approaches aimed at immune-mediated mechanisms of antitumor activity that remain viable options include dendritic cell vaccines, tumor cell vaccines and engineered T-cells that target tumor cells directly [ 18 – 20 ].…”