Dendritic cell-based vaccine in advanced melanoma

Abstract

Dendritic cells (DCs) are unique specialized antigen-presenting cells capable of priming naive T cells and inducing antigen-specific cytotoxic T lymphocytes. This study presents an update of clinical results from a DC-based phase I-II clinical vaccine trial in stage IV melanoma. From 2003 to 2010, 27 patients with metastatic melanoma were treated with mature DCs pulsed with autologous tumor lysate and keyhole limpet hemocyanin and with subcutaneous low-dose interleukin-2. Delayed-type hypersensitivity (DTH) tests for in-vivo immunomonitoring were performed at baseline and every four vaccinations thereafter. Two complete, two mixed and six partial responses, and five stable diseases were observed (overall response, 37.0%; clinical benefit, 55.5%). All 15 responders showed DTH positivity. A median overall survival of 22.9 months [95% confidence interval (CI): 13.4-61.3] for DTH-positive patients (19) and 4.8 months (95% CI: 3.9-11.9) for DTH-negative patients (8; log rank=7.26; P=0.007) was observed. The overall median overall survival was 16 months (95% CI: 9-33). Our results would seem to highlight a relationship between positive-DTH test and an improved survival.

Vaccination with autologous dendritic cells loaded with autologous tumor lysate or homogenate combined with immunomodulating radiotherapy and/or preleukapheresis IFN-α in patients with metastatic melanoma: a randomised “proof-of-principle” phase II study

“…Like de Vries et al [17], we saw that patients who developed anti-tumor immunity after vaccination experienced a better clinical outcome [16,18]. In particular, we observed that patients developing delayed type hypersensitivity (DTH) against autologous tumor lysate or keyhole lympet hemocyanin (KLH) after at least four courses of the vaccine showed a median overall survival (OS) of 22.9 months compared to the 4.8 months of DTH-negative cases (Log-rank test, p = 0.007) [16].…”

“…Since 2001, patients with advanced melanoma enrolled onto our phase II clinical studies have been administered autologous DC loaded with autologous tumor lysate/homogenate matured with a cytokine cocktail, showing a clinical benefit (PR + SD) in 55.5% of evaluable cases [15,16]. …”

“…In particular, we observed that patients developing delayed type hypersensitivity (DTH) against autologous tumor lysate or keyhole lympet hemocyanin (KLH) after at least four courses of the vaccine showed a median overall survival (OS) of 22.9 months compared to the 4.8 months of DTH-negative cases (Log-rank test, p = 0.007) [16]. Intriguingly, both the disease control rate (DCR) and OS obtained with DC vaccination considerably exceeded those obtained with ipilimumab in a similar patient setting [4].…”

“…Since 2001, IRST Somatic Cell Therapy Laboratory has produced an advanced medicinal product in the form of a therapeutic vaccine composed of autologous DC pulsed with autologous tumor lysate or homogenate for patients with metastatic melanoma or kidney cancer [15,16,38-40]. The vaccine can be administered to patients either immediately after preparation or after thawing of cryopreserved aliquots.…”

Dinitrophenyl hapten with laser immunotherapy for advanced malignant melanoma: A clinical study

“…Cutaneous DTH could be used as an indicator to evaluate immune therapy (35), as well as being a predictor of survival (36). In 27 patients with stage IV MM receiving a DC vaccine to induce DTH, the median survival time was 22.9 months (n=19) in DTH-positive patients and 4.8 months in DTH-negative patients (37). Similarly, in the present study, the extent of the DTH reaction was associated with OS and DFS.…”