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Prostate Cancer

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Substantial remission of prostate adenocarcinoma with dendritic cell therapy APCEDENR in combination with Chemotherapy

Cancer type:
Prostate adenocarcinoma. PSA level of 82.17 ng/ml with a GLEASON score of 8 and classified as T1cN1M1b stage of prostate cancer.

Patient conditions: A 63-year-old male with metastatic prostate adenocarcinoma and previous failed treatment history of standard hormonal, chemo, and radiotherapy regimens.

Treatments:
Administration of personalized dendritic cell-based vaccine APCEDENR in combination with anthracenedione antineoplastic drug Mitoxantrone. APCEDEN is an autologous DC formulation in which DCs are derived from CD14+ blood monocytes as previously described by Romani et al. and loaded with whole-tumour lysate. Each dose of the vaccine is divided and administered via intravenous and intradermal routes. Six doses of APCEDEN were given at 15-day intervals in a time frame of 3 months.

Results:
Substantial remission. More than 60% reduction in size of the lesions in the left para-aortic, mediastinal, and right supraclavicular nodes. Remarkable remission of skeletal metastases. Lower serum PSA level of 8 ng/ml post-APCEDEN.
After dose 4 and 6, the patient showed an increased amount of IFN-γ-expressing CD4+ T lymphocytes along with a decrease in CD4+ and CD8+ Tregs in peripheral blood. However, post-immunotherapy the patient received six cycles of mitoxantrone, an ‘antineoplastic’ or ‘cytotoxic’ chemotherapy drug, from July 2017 to October 2017, as he had an advanced hormone-refractory prostate cancer due to hormonal therapy failure earlier in the treatment history.

Conclusion:
The current case report suggests autologous DC immunotherapy could form a safe, feasible and efficacious therapy in combination with the systemic chemotherapy drug mitoxantrone, providing a step forward toward an evolving chemoimmunotherapy approach for cancer treatment. DC vaccine optimization through effective antigen presentation strategies and operational combination therapy strategies are the foci of ongoing and upcoming studies.

Reference:
Podrazil1 M., Horvath R., Becht E., Rozkova D., Bilkova P., Sochorova K., Hromadkova H., Kayserova J., Vavrova K., Lastovicka J., Vrabcova P., Kubackova K., Gasova Z., Jarolim L., Babjuk M., Spisek R., Bartunkova J., Fucikova J.
Phase I/II clinical trial of dendritic-cell based immunotherapy (DCVAC/PCa) combined with chemotherapy in patients with metastatic, castration-resistant prostate cancer
Oncotarget (2015) 6(20), 18192-18205

Blood-derived dendritic cell vaccinations induce immune responses that correlate with clinical outcome in patients with chemo-naive castration-resistant prostate cancer

Cancer type:
Castration-resistant prostate cancer (CRPC). Adenocarcinoma of the prostate.

Patient conditions: Eligible patients had not received any immunotherapy, docetaxel, cabazitaxel or treatment with the RANKL-inhibitor denosumab. Also, patients had no visceral metastases.

Treatments:
21 chemo naive CRPC patients received maximally 9 vaccinations with mature myeloid dendritic cells (mDCs), plasmacytoid (pDCs) or a combination of mDCs plus pDCs. One cycle of vaccinations consisted of three biweekly vaccinations administered intranodally in a clinically tumour-free lymph node.

Results:
IFN-γ+ antigen-specific T cells median radiological progression free survival (rPFS) was 18.8 months (n= 5) vs. 5.1 months (n= 16) in patients without IFN-γ-producing antigen-specific T cells (p= 0.02). The overall median rPFS was 9.5 months.
All DC vaccines were well tolerated with grade 1–2 toxicity. Most frequent grade 1–2 toxicity included flu-like symptoms, fatigue, upper respiratory infections, dizziness, vaccination-induced hematomas and injection site reactions.

Conclusion:
Immunotherapy with bloodderived DC subsets was feasible and safe and induced functional antigenspecific T cells. The presence of functional antigenspecific T cells correlated with an improved clinical outcome.

Reference:
Podrazil1 M., Horvath R., Becht E., Rozkova D., Bilkova P., Sochorova K., Hromadkova H., Kayserova J., Vavrova K., Lastovicka J., Vrabcova P., Kubackova K., Gasova Z., Jarolim L., Babjuk M., Spisek R., Bartunkova J., Fucikova J.
Phase I/II clinical trial of dendritic-cell based immunotherapy (DCVAC/PCa) combined with chemotherapy in patients with metastatic, castration-resistant prostate cancer
Oncotarget (2015) 6(20), 18192-18205

Survivin and PSMA Loaded Dendritic Cell Vaccine for the Treatment of Prostate Cancer

Cancer type:
Hormone refractory prostate cancer (HRPC).

Patient conditions:
A total of 21 HRPC patients with a life expectancy >3 months were randomised into two groups.
Treatment group consisting of autologous dendritic cell vaccine (n=11) and control group consisted of patients receiving docetaxel plus prednisone (n=11). Only patients with serum prostate specific antigen (PSA) between 10–100 ng/mL after radical prostatectomy for T1–T3, N0, M0 prostate adenocarcinoma were included in the study.

Treatments:
DC loaded with recombinant Prostate Specific Membrane Antigen (rPSMA) and recombinant Survivin (rSurvivin) peptides (ratio 1:1). Patients received 5 doses of 5×106 DCs in each dose and administered as a subcutaneous injection. The first three doses were administered at a gap of 15 days and last two doses were administered at a gap of 30 days. Control group patients received docetaxel (75 mg/m2 intravenously over 1 hour every 21 days [one cycle]) and prednisone per os (5 mg bis in die on days 1–21).

Results:
IFN-γ+ antigen-specific T cells median radiological progression free survival (rPFS) was 18.8 months (n= 5) vs. 5.1 months (n= 16) in patients without IFN-γ-producing antigen-specific T cells (p= 0.02). The overall median rPFS was 9.5 months.
All DC vaccines were well tolerated with grade 1–2 toxicity. Most frequent grade 1–2 toxicity included flu-like symptoms, fatigue, upper respiratory infections, dizziness, vaccination-induced hematomas and injection site reactions.

Conclusion:
Immunotherapy with bloodderived DC subsets was feasible and safe and induced functional antigenspecific T cells. The presence of functional antigenspecific T cells correlated with an improved clinical outcome.

Reference:
Podrazil1 M., Horvath R., Becht E., Rozkova D., Bilkova P., Sochorova K., Hromadkova H., Kayserova J., Vavrova K., Lastovicka J., Vrabcova P., Kubackova K., Gasova Z., Jarolim L., Babjuk M., Spisek R., Bartunkova J., Fucikova J.
Phase I/II clinical trial of dendritic-cell based immunotherapy (DCVAC/PCa) combined with chemotherapy in patients with metastatic, castration-resistant prostate cancer
Oncotarget (2015) 6(20), 18192-18205

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