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.

Substantial tumor regression in prostate cancer patient with extensive skeletal metastases upon Immunotherapy (APCEDEN): A case report.

RATIONALE: Prostate cancer along with colorectal and lung cancers accounts for 42% of cancer cases in men globally. It is the first cancer indication for which the use of active immunotherapy, Sipuleucel-T (Provenge) was granted by the FDA in 2010. This study presents a case of prostate carcinoma and the tumour remission observed after administration of a personalised Dendritic cell vaccine (APCEDEN). PATIENT CONCERNS: A 58 years old Caucasian male diagnosed with prostate carcinoma with GLEASON score 8. The patient had previously been diagnosed with Renal Cell Carcinoma (RCC) in 1996 and had undergone nephrectomy of the right kidney. PET CT scan revealed multiple intensely PSMA avid lesions noted in both lobes of the prostate gland with SUVmax -28.3 and the prostate gland measuring 3.2 × 3.2 cm displaying maximum dimensions. DIAGNOSIS: FNAC followed by PETCT confirmed CA Prostate and further supported by increased serum PSA level. INTERVENTIONS: The patient underwent personalised Dendritic Cell Immunotherapy APCEDEN regimen of six doses biweekly, in a time frame of 3 months were given both via intravenous and intradermal route. Six months post completion of APCEDEN, the patient was administered 6 booster shots for 6 months. OUTCOMES: Progressive remission of carcinoma was observed along with reduction in PSA and Testosterone levels. PET CT showed decline in PSMA avidity by 50% with SUVmax -14.0 and normal size and shape of prostate gland. LESSONS: Prostate carcinoma is the second most common cancer in men with majority of them exhibiting locally advanced disease. Apparently 20% to 30% of them are categorized as relapsed cases after various therapeutic interventions. Modulating immune system is an emerging therapy termed as Immunotherapy and potentiates the killing cancer cells via immune activation. Interestingly, prostate cancer is slow growing and it provides the scope and time to mount an anti-tumor response which makes it an attractive target for immunotherapy. This case study demonstrates the efficacy of APCEDEN Immunotherapy regimen resulting in a significant disease remission benefiting the patient.

Substantial remission of prostate adenocarcinoma with dendritic cell therapy APCEDEN® in combination with chemotherapy.

Of the most prevalent solid tumors with advanced disease, prostate and ovarian cancer and non-small cell lung carcinoma have the fewest therapeutic options. Herein, we report the case of a 63-year-old male with metastatic prostate adenocarcinoma showing substantial remission post-administration of personalized dendritic cell-based vaccine APCEDEN® in combination with chemotherapeutic drug Mitoxantrone. Therapeutic response displayed an interesting clinical correlation validated by PET scan images showing decreased fluorodeoxyglucose (FDG) avidity in the prostate gland, reduced skeletal metastases further established by the drop in serum Prostate Specific Antigen (PSA) levels and expression of immune assessment markers (IFN-γ, Tregs, neutrophil lymphocyte ratio and platelet lymphocyte ratio). This case demonstrates the potential efficacy of dendritic cell immunotherapy, showing a potent antitumor activity by enhancing the host immune responses, and improving quality of life.

Complete remission of rare adenocarcinoma of the oropharynx with APCEDEN® (dendritic cell-based vaccine): a case report.

APCEDEN ® is an autologous monocyte-derived dendritic cell-based immunotherapy. A 58-year-old man with adenocarcinoma of oropharynx shows complete remission after receiving APCEDEN ® in conjunction with Geftinib validated by reduction in size, whereas Gefitinib alone lead to disease progression.

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.

Characterization of aeromonads isolated from the river Narmada, India.

Thirty isolates of Aeromonas species were isolated from river Narmada at Jabalpur during the period of January 2002-December 2002. Diversity of these fresh water isolates were determined by randomly amplified polymorphic DNA (RAPD) analysis. These environmental isolates were found to be positive for virulence factors, i.e. protease, amylase, lipase and DNase. Isolates were also positive for beta-hemolytic activity. All Aeromonas species were tested for antibiotic resistance patterns and were found to be resistant to ampicillin and sensitive to gentamycin.