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Lunch & Poster Display session

44P - Evaluation of immune response in young patients with sarcoma treated by dendritic cell-based immunotherapy

Date

12 Dec 2019

Session

Lunch & Poster Display session

Presenters

Lenka Fedorova

Citation

Annals of Oncology (2019) 30 (suppl_11): xi12-xi15. 10.1093/annonc/mdz448

Authors

L. Fedorova1, L. Zdrazilova Dubska2, I. Selingerova1, K. Pilatova2, P. Mudry3, J. Sterba3, R. Demlova2, D. Valik2

Author affiliations

  • 1 Department Of Laborory Medicine, Masaryk Memorial Cancer Institute, 656 53 - Brno/CZ
  • 2 Department Of Pharmacology, Masaryk University, Faculty of Medicine, 62500 - Brno/CZ
  • 3 Department Of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, 61300 - Brno/CZ
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Resources

Abstract 44P

Background

Individually prepared immunotherapy (ITx) based on autologous dendritic cells (DCs) represents a new possibility in modern advanced anti-cancer treatment. As an extended evaluation of DC-based medicinal product in an academic phase I/II clinical trial for children, adolescents and young adults with progressive, recurrent or primarily metastatic high-risk tumors (EudraCT 2014-003388-39), we performed the examination of T-cell stimulatory properties and detailed peripheral blood immunomonitoring.

Methods

Ten patients (6 female, 4 male, median age 19 years) with relapsing sarcomas disease were treated with DCs pulsed with self-tumor antigens. DC ITx was administered intradermally in 2-4 week intervals. Peripheral blood was collected at baseline, after 5th, 9th and 13th dose. Nine circulating immune markers were quantified by flow cytometry: absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), effector CD8+T-cells, activated CD8+ T-cells, γδ T-cells (GD), monocytic MDSC, regulatory T-cells, NK, and NKT-like cells. DC stimulatory properties were examined by autologous mixed lymphocyte reaction using patient T-cells obtained before DC vaccination (pre-DC) and after min 5th doses of DCs (post-DC). The stimulation was expressed as % of the division after DC stimulation.

Results

ALC was baseline low in 9 of 10 cases and 6 of 10 cases were connected to high (>3) NLR with no significant changes during DC ITx. We observed decrease of NKT-like (p = 0.04) and elevation of GD (p = 0.008) after 13th dose compared to baseline. Post-DC auto-MLR was higher compared to pre-DC in all sarcoma study patients. The median patient T-cell stimulation increased from 8.8% with pre-DC T-cells to 14.6% division with post-DC T-cells.

Conclusion

Circulating cell-based immune markers revealed dose-dependent changes in subtle T-cell subsets during the course of DC treatment. Personalized anti-cancer DC-based ITx stimulates a pre-existing immune response against self-tumor antigens.

Clinical trial identification

EudraCT: 2014-003388-39.

Editorial acknowledgement

Legal entity responsible for the study

Czech Ministry of Health.

Funding

Czech Ministry of Health (Projects LO1413, LM2015090, academic clinical trial).

Disclosure

All authors have declared no conflicts of interest.

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