Substantial remission of Prostate Adenocarcinoma with Dendritic Cell Therapy APCEDEN® in combination with Chemotherapy

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Introduction

Prostate cancer (PCa) is the most frequently diagnosed non-cutaneous malignancy in elderly men and is the second leading cause of cancer-related death in Western countries. Localized, early- stage disease is, in general, successfully treated with surgery or radiation therapy; however, approximately 30% of patients have recurrence and require further management. Cancer immunotherapy is being tested as an additional treatment modality in oncology. Active cellular immunotherapy (ACI) using antigen-loaded dendritic cells (DCs) is another immunotherapeutic approach in the clinical development. The concept of combined chemoimmunotherapy explores the fact that the treatment with chemotherapy might not only decrease the tumor cell load but also neutralize the tumor induced immunosuppression thus facilitating the effect of concurrent immunotherapy.
Active immunotherapy utilizing dendritic cells (DCs) loaded with tumor antigen ex vivo results in eliciting tumor-specific T-cell-mediated tumor cell toxicity. Antigen-loaded DCs have been tested in multiple clinical trials as therapeutic vaccines. Varied formulations of DC vaccines utilizing alternative sources of tumor-associated antigens along with other adjuvants are also under experimentation to target early stages of tumor development.

Methodology

• Separation of peripheral blood mononuclear cells by apheresis and further isolation of monocytes from apheresis harvest by plastic adherence; culturing in RPMI-1640 media supplemented with IL-4 and GM-CSF and autologous plasma in vitro.
• On the 6th day, exposure of the patient’s own tumor lysate and supplemented with PolyI:C was used as maturation stimuli; after 3 hours of adding PolyI:C, 1-20 ug/ml protein was loaded on DCs.
• On the 8th day, mature DCs were harvested and packed as six doses (4-5 million mature DCs per dose)

 

Therapy

The DC vaccines were administered via intravenously (IV) and intradermally (ID) routes. Six doses of APCEDEN were given at 15-day intervals (fortnightly) in a time frame of 3 months.Case Presentation
In 2011, a 63-year-old male was diagnosed with prostate adenocarcinoma. PET scan revealed an enlarged prostate gland measuring 48x45x40 mm and a high serum PSA level of 82.17 ng/mL with a GLEASON score of 8. He was given neoadjuvant hormonal therapy in the form of Inj Goserelin 10.8 mg twice (first dose in November 2011 and second dose in February 2012) which resulted in complete resolution of bilateral iliac and para-aortic nodes. He underwent radiation therapy for 14 months. In July 2015, six cycles of chemotherapy in the form of docetaxel were administered to reduce the observed post-radiation tumor progression to lymph nodes and skeletal metastasis. From March 2016 – November 2016, the therapy was followed by abiraterone, which is an effective therapy option primarily intended to treat metastatic prostate cancer that has metastasized to other parts of the body. In November 2016, he received 10 cycles of palliative radiation therapy to alleviate obstructive urinary symptoms, tenesmus, and pain. In December 2016, he was re-administered with docetaxel, which was stopped as he developed neutropenia and increase the risk of infection. After consulting his oncologist, he chose to receive APCEDEN, an autologous dendritic cell immunotherapy.

 

Results

Post the APCEDEN immunotherapy regimen of six doses administered fortnightly from February 2017 to May 2017. PET-CT scan in the following May 2018 did not reveal any appearance of significant avidity in the prostate gland with more than 60% reduction in size of the lesions in the left para-aortic, mediastinal and right supraclavicular nodes.
Positive response to immunotherapy was also supported by a lower serum PS level of 8 ng/mL post-APCEDEN. The NLR and PLR for the patient were also seen to decrease during the course of the therapy. The immune assessment of the patient was done at the baseline and after the dose 4 and 6, which showed an increased amount of IFN-y-expressing CD4+ T lymphocytes along with the decrease in CD4+ and CD8+ Tregs in peripheral blood. Further, he was administered ommanacortil 5 mg (corticosteroid), ketoconazole 200 mg from November 2017 until May 2018.

 

Conclusion

Immunotherapy along with modern antiandrogen therapies has the potential to severely impact the survival of patients with prostate adenocarcinoma. The autologous DC vaccine APCEDEN has been reported as safe and shown significant improvement in the quality of life of cancer patients. This case study illustrates the benefits of immunotherapy in prostate cancer patients when used as an adjunct therapy to existing line of treatment regimens after a brief pseudo progression.

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Scientific article publishing date : 29/10/2019

Immucura identifier : BSC21_015EN

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