Assessment of Immune Response Following Dendritic Cell-Based Immunotherapy in Pediatric Patients With Relapsing Sarcoma

PET/CT imaging

PET/CT imaging

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Summary

This study focuses on high-risk sarcoma patients representing a major diagnosis in this clinical trial. First, we evaluated quantitative association between basic cell-based immune parameters. Next, we described patterns of these parameters and their time changes during the DC vaccination course in the peripheral blood immunograms. We evaluated immune response of patient T-cells to the tumor antigens presented by DCs in autoMLR proliferation assay. This analysis was performed with T-cells obtained prior to DC ITx initiation and with T-cells collected after administration of the fifth dose of DCs. Finally, we presented clinical and immunological findings from DC-based ITx after relapse in the case of the Ewing’s sarcoma patient.

Patients characteristics

• Patients with histologically confirmed refractory, relapsing or primarily metastatic high- risk tumors.
• Karnofsky or Lansky score ≥50.
• Patients must have adequate function of bone marrow, kidney, liver and heart.
• Patients must not have severe ongoing toxicity resulting from any previous treatment.
• 47 patients enrolled in this study, due to some complications only 19 patients were given DC vaccines.
• Of these 19, 9 patients with Sarcomas (2 with Ewing sarcoma, 4 with Osteosarcoma, 1 with Alveolar Rhabdomyosarcoma, 1 with embroyomal rhabdomyosarcoma, 1 synovial sarcoma).

Methodology

• Mononuclear cells were collected by leukapheresis and then monocytes were separated by elutriation or adherence to a plastic surface.
• Harvested monocytes were cultivated with IL-4 and GM-CSF and differentiated into DC.
• Immature DCs were subsequently exposed to autologous tumor lysate antigens.
• Maturation was induced by lipopolysaccharide and interferon-y.

Treatment

DC-based IMP was administered intradermally (ID) every 3 ± 1 weeks, up to 35 doses to a predefined site on the left or right arm near the axillary lymph node. Administration of topical Imiquimod before and 2 evenings after vaccination in the injection site. Each dose of DC is 2×106.

Results

• No immune or infection-related AESIs were reported for all patients.
• 1 patient with Ewing sarcoma achieved complete remission (CR) Karnofsky 100.
• 3 patients achieved partial response (PR).
• 1 with Ewing sarcoma (Karnofsky 100).
• 1 with Alveolar Rhabdomyosarcoma (Karnofsky 80).
• 1 with Embryonal Rhabdomyosarcoma (Karnofsky 70).
• 1 patient with Osteosarcoma achieved stable disease (SD) (Karnofsky 90).
• 4 patients with progressive disease (PD).

Conclusion

Anticancer DC vaccination could be more effective if appropriately personalized not only in terms of loading DC with self- tumor antigens but also in terms of selection of the right patients that would benefit from ITx (such as patients with tumor with high mutational load), and treatment at the right time when the disease and the level of immune suppression is minimal, and selection of right (possibly personalized) concomitant treatment that allows the optimal immunostimulant and anticancer activity of effector cells. In this study shows that DC immunotherapy is effective and shows clinical outcomes in patients with Ewing sarcoma.

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Scientific article publishing date 14/11/2019

Immucura identifier BSC21_039EN

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