8PD - Dendritic cell production from allogenenic donor Cd34+ stem cells and mononuclear cells: Cancer vaccine

Date 05 November 2016
Event ESMO Symposium on Immuno-Oncology 2016
Session Poster discussion session
Presenter Ali Unal
Citation Annals of Oncology (2016) 27 (suppl_8): viii2-viii4. 10.1093/annonc/mdw526
Authors A. Unal1, A. Birekul1, M.C. Unal1, E. Karakus1, Y. Koker1, Y. Ozkul2, F.M. Comu3
  • 1Hematology, Erciyes University Medical Faculty M.Kemal Dedeman, Oncology Hospital, 38039 - Kayseri/TR
  • 2Clinical Genetics, erciyes university medical faculty, 38039 - Kayseri/TR
  • 3Physiology, kirikkale university medical faculty, kirikkale/TR

Abstract

Aim/Background

Active immunotherapy provides better recognition of tumor-related antigens by immune systems of patients, enhanced immune system and elimination of malignant cells. This modality employs the therapeutic potential of donor and tumor-specific immune responses. Active immunotherapy targets immunosuppressive and tolerogenic mechanisms suppressed by tumor cells. T lymphocytes and antigen-presenting cells (dendritic cells) are two cell lineages that play crucial roles in the battle of organism against cancer. Close similarity between cancer cells and normal cell structure is the most important cause of escape from T lymphocytes.

Methods

To generate allogeneic dendritic cells (DC), leukemic stem cells were isolated from bone marrow samples from patients with acute leukemia. Lysate was prepared from leukemic stem cells identified by flow cytometer. Stem cells and mononuclear cells (1×10>6/kg) obtained from sibling donors by apheresis were separated to produce DC. For DC transformation, GM-CSF and IL-4 were added to media where leukemic stem cell lysate from patient and mononuclear cells from sibling donor were treated. From samples taken from the culture medium, after 48, 72 and 96 hours, DC surface markers (CD 80, CD 83 and CD 86) was assessed by flow cytometry. CD3, CD14, CD19, CD56, CD66b-negative, and HLA-DR, CD86 positive are indicative of immature DC. HLA-DR, CD 80 and CD83 positive are indicative of mature DC.

Results

Mononuclear cells were detected at 27% among allogeneic hematopoietic cell groups harvested by apheresis. After culture under GMP conditions, mononuclear cell rate was found to be 24% on hours 96 and 120. It was seen that 88% of mononuclear cells transformed to mature dendritic cells after 96 hours culture.

Conclusions

In cancer patients, minimal residual disease can be eliminated by active tumor vaccine after reducing tumor burden by standard methods. Tumor vaccine obtained from allogeneic sibling donor can be used in lieu of autologous tumor vaccine and it is thought to be more effective. Allogeneic dendritic cells produced at 37°C in CO2 media under GMP conditions can be used in tumor immunotherapy. A more effective method would be to use dendritic cells against cancer stem cells rather than cancer cells itself.

Clinical trial identification

Legal entity responsible for the study

Ali Unal

Funding

Erciyes University Mehmet Kemal Dedeman Oncology Hospital

Disclosure

All authors have declared no conflicts of interest.