Open-label, multi-center, non-randomized, single-arm study to evaluate the safety and efficacy of dendritic cell immunotherapy in patients with refractory solid malignancies, on supportive care.

BACKGROUND AIMS: A phase II clinical trial of an autologous dendritic cell (DC) formulation for the management of refractory solid malignant tumors was conducted across six sites in India with an objective to study safety and efficacy. METHODS: A total of 51 patients with refractory cancer (either sex) with life expectancy ≥3 months, Eastern Cooperative Oncology Group score ≤2, available tumor tissue and adequate organ and bone marrow function were recruited. Monocytes obtained by leukapheresis, differentiated into DCs by cytokines and primed with autologous tumor lysate (fresh tissue biopsy or paraffin block). On the 8th day, mature DCs were analyzed for expression of CD40, CD80, CD83, CD86, DC205 and DC209. The treatment regime consisted of six doses (intravenous) over 14 weeks with 2 post-treatment follow-up visits, 6 weeks apart. Safety was assessed at all visits and responses were evaluated on days 58, 100 and 184 or at end of the study. RESULTS: A total of 38 patients were evaluated for safety and efficacy. One adverse event classified as possibly related was an episode of rigors or chills with mild pyrexia during one infusion. Objective response rate by Response Evaluation Criteria In Solid Tumors was 28.9% (11/38) and immune-related response criteria was 42.1% (16/38); 90% confidence interval for objective response rate was (17.2, 43.3) and (28.5, 56.7) by Response Evaluation Criteria In Solid Tumors and immune-related response criteria, respectively. The median time to treatment progression was >9 weeks. Median overall survival was 397 days. An increase in the expression of interferon-γ was not significant. CONCLUSIONS: Therapy was safe. The responses, time to treatment progression and survival are encouraging for patients with aggressive refractory disease.

Immune modulation by dendritic-cell-based cancer vaccines.

The interplay between host immunity and tumour cells has opened the possibility of targeting tumour cells by modulation of the human immune system. Cancer immunotherapy involves the treatment of a tumour by utilizing the recombinant human immune system components to target the pro-tumour microenvironment or by revitalizing the immune system with the ability to kill tumour cells by priming the immune cells with tumour antigens. In this review, current immunotherapy approaches to cancer with special focus on dendritic cell (DC)-based cancer vaccines are discussed. Some of the DC-based vaccines under clinical trials for various cancer types are highlighted. Establishing tumour immunity involves a plethora of immune components and pathways; hence, combining chemotherapy, radiation therapy and various arms of immunotherapy, after analysing the benefits of individual therapeutic agents, might be beneficial to the patient.

A retrospective analysis comparing APCEDEN® dendritic cell immunotherapy with best supportive care in refractory cancer.

AIM: A retrospective survival benefit analysis of APCEDEN®, APAC BIOTECH Pvt Ltd 69, Jacranda Marg, DLF PHASE II, Gurugram, Haryana, India, an autologous dendritic cell-based product for management of refractory solid malignancies, was performed in comparison with a control group. METHODS: Subjects (retrospective data) whose survival data, geographical region, age, gender, ECOG performance status and stage of disease that could be matched with the treatment group were considered for analysis. RESULTS: The analysis suggests a significant survival benefit of 199 days for the APCEDEN therapy treatment group when compared with the control group (356 vs 157 days). The event-free survival time of APCEDEN therapy was 439 days in patients who demonstrated an objective response at first evaluation as per immune-related response criteria. CONCLUSION: APCEDEN demonstrated highly convincing survival benefits when compared with the control group.