Phase 1/2 Study of Immunotherapy With Dendritic Cells Pulsed With Autologous Tumor Lysate in Patients With Refractory Bone and Soft Tissue Sarcoma

Before and after immunotherapy

Before and after immunotherapy

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Summary

The purpose of this study was to assess the immunological and clinical effects of dendritic cells (DCs) pulsed with autologous tumor lysate (TL) in patients with advanced bone and soft tissue sarcomas. DC therapy appears safe and resulted in an immunological response in the patients.

Patients characteristics

37 patients were enrolled in the study 17 patients with bone tumors
20 patients with Soft tissue Sarcoma.
(5 with malignant Fibrous Histiocytomas, 4 with Clear Cell Sarcoma, 2 with Synovial Sarcoma, 3 with Leiomyosarcoma, 1 Ewing Sarcoma, 1 with Liposarcoma, 1 with Alveolar soft part sarcoma, 1 with Angiosarcoma, 1 Ependymomas, 1 with malignant Peripheral nerve sheath tumor).

Methodology

• Dendritic cells were prepared from blood monocyte precursors from the patients
• To isolate peripheral blood mononuclear cells, PBs was centrifuged with
Lymphoprep tubes.
• Subsequently, the PBMC were plate in 6-well dishes at 1-4×107 cells in 2 mL per well for 2 hours.
• To generate DC, the adherent cells in the dish were cultured in serum free media containing Penicillin G, Streptomycin, recombinant human IL-4 and recombinant GM-CSF for 7 days.
• The DC divided into 3 groups and treated with several combination of tumor lysate, TNF-a, OK-432.
• On day 4 and 5, the cultures were additional supplemented with or without TL, OK-432 and TNF-a
• On day 7, the DCs at 3 groups were collected and mix of normal saline.

Treatment

The DC vaccine were subcutaneously (SC) injected into the inguinal or axillary region in 6 weekly.

Results

• No adverse effects associated with the DC based immunotherapy were observed in all the patient level were observed 1 month after the DC injection.
• Increased in serum IFN-y and IL-2
• Within 3 months after the treatment, 4 patients (2 OS, 1 CCS, 1 PNST,) exhibit
progressive disease (PD)
• After 8 weeks of DC vaccine, 1 patient (2.9%) achieved partial response (PR), 6 (17.1%) patients exhibit stable disease (SD) and 28 (80.0%) developed progressive disease (PD)
• During the follow-up period, 27 patients received other treatments like Chemotherapy, Mastectomy and Radiotherapy.
• 3-year overall survival rate of all the patient is 42.3% and progression-free survival (PFS) of 2.9%.

Conclusion

In conclusion, the findings of our phase 1/2 trial indicate that a regimen consisting of DC immunotherapy using TL and OK-432 was safe and could induce immunological responses in patients with refractory sarcoma.

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Scientific article publishing date 2/17/2017

Immucura identifier BSC21_306EN

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