Blood-derived Dendritic Cell Vaccinations Induce Immune Responses that Correlate with Clinical Outcome in Patients with Chemo-naive Castration-resistant Prostate Cancer

Tumour size before and after treatment

Tumour size before and after treatment

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Summary

A study involving patients with Castration-resistant Prostate cancer showed that the the immunological response and outcome of vaccination with dendritic cells was feasible and safe. The immunotherapy with blood-derived dendritic cells induced functional antigen-specific T cells that correlated with an improved clinical outcome.

Introduction

The study involved 21 patients with Castration-resistant Prostate cancer are in this trial. All patients had not received any immunotherapy, docetaxel, cabazitaxel or treatment with the RANKL-inhibitor denosumab. Patients had no visceral metastasis.

Absence of active autoimmune diseases, absence of an active viral infection or allergy to shellfish; and no significant laboratory abnormalities. Adequate bone marrow, liver and renal function.

Methodology

21 chemo naive CRPC patients received maximally 9 vaccinations with mature myeloid dendritic cells (mDCs), plasmacytoid (pDCs) or a combination of mDCs plus pDCs.

Treatment

One cycle of vaccinations consisted of three biweekly vaccinations administered intranodal in a clinically tumor-free lymph node.

Results

Safety and adverse events:

DC vaccinations were well tolerated. In all vaccinated patients only low-grade toxicity (CTCAE grade 1–2) was noticed. Most frequent grade 1–2 toxicity included flu- like symptoms, fatigue, upper respiratory infections, dizziness, vaccination-induced hematomas and injection site reactions. Also, some low-grade laboratory adverse events were seen.

Clinical outcome:
Of the 21 included patients, in 1 patient (5%) a partial radiological response was observed. Stable disease
that persisted > 6 months was seen in 12 patients (57%). In 8 patients (38%) disease progression was observed within 6months. Median rPFS for all patients was 9.5months (range: 3.2–24.8* months). The 6- and 12-months rPFS was 62% and 29%, respectively. There was no significant difference between the three treatment arms; in the mDC group the rPFS was 12.0months (range 3.4–24.8* months), in the pDC group 10.7 months (range 3.4–23.9* months) and 4.2 months (range 3.2–12.0 months) in the combiDC group.

A decrease in PSA level was detected only in 2 of 21 patients. One of these patients (combiDC- 07) showed a > 99% PSA-decrease which co-occurred with a partial radiological response. Median OS was not reached. The median follow-up of all patients is 27.2months (range 10.7– 41.2* months).Clinical outcome related to immunohistochemical results.

Patients with TAA-specific T cells whose tumor expressed the same TAA (dm+ and tumor+; n = 5) had a median rPFS of 10.7 months (range: 9.5–24.8*). Patients that did not have matching TAA-specific T cells and TAA-expression of the tumor (dm+/− and tumor−; n = 16), had a median rPFS of 5.2 months (range: 3.2–24.3*). This difference was not statistically significant. In two patients who progressed after DC vaccination, loss of MUC1 expression by the tumor was observed. In one of these patients, MUC-1-specific T cells were detected. Tumor PD-L1 expression was studied in 10 patients. In two of these patient’s tumor PD-L1 expression post-vaccination was ≥1%.
One of them was a dm+ and IFN-γ+ patient showing tumor PD-L1 expression of 60%. Tumors of all biopsied patients were microsatellite stable.

Conclusion

Immunotherapy with blood-derived DC subsets was feasible and safe and induced functional antigen- specific T cells. The presence of functional antigen-specific T cells correlated with an improved clinical outcome.

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Scientific article publishing date : 6/3/2019

Immucura identifier : BSC21_027EN

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