Dendritic Cell Vaccine for Relapsed Neuroblastoma

At the beginning of 2013, the newswires and social networks lit up with the news that a vaccine targeted to kill neuroblastoma cells had put a patient into remission.  The case study was published in the high-impact journal “Pediatrics”. This work built on five years of pre-clinical research, resulting in some very promising new immunological targets for neuroblastoma.  The project was partially funded by a joint grant from the Andrew McDonough B+ Foundation, Pierce Phillips Charity and Solving Kids’ Cancer.

As much as this is encouraging, it is also valuable to understand some details of the case.  Most importantly, this report is about only one patient in the larger study that is currently ongoing at University of Louisville (Kosair Children’s) and at Dana-Farber (Boston Children’s).  The paper is a “case report” which is distinct from clinical research reports that discuss results of all patients on a study. Evidence-based medicine in clinical research is built on the results of many patients, and conclusions from single case studies should be taken as anecdotal.

Immune cells (dendritic cells) were collected from the patient, pulsed with CT (cancer testes) antigens, and grown in the laboratory to return to the patient as a vaccine injection in several doses. The dendritic cells “teach” the patient’s T cells to recognize the neuroblastoma cells with the CT antigens.  Before receiving the vaccine, the patient was treated with chemotherapy (decitabine) to increase the expression of the CT antigens on the neuroblastoma cancer cells (Krishnadas et al, 2013).  This type of immunotherapy is different from other approaches using antibodies such as ch14.18 that target GD2 which is also found on the surface of neuroblastoma tumor cells.

This case is about one patient who was diagnosed with neuroblastoma (unfavourable, not MYCN amplified) at 3 years of age with a primary tumor, bone marrow involvement, and bony metastases (found by PET scan); however, HVA/VMA and MIBG scans were negative.  The patient did not respond completely to frontline therapy (COG- ANBL0532 protocol), and at the end of treatment which included ch14.18 immunotherapy, the patient’s final tests showed disease in the bone marrow.  This disease persisted even after three cycles of irinotecan and temozolomide.

The patient had his “peripheral blood mononuclear cells collected via apheresis for the culture of dendritic cells” (Krishnadas et al. 2013, p. e338) and then began the decitabine chemotherapy.  The patient received 3 cycles of the protocol: decitabine for 5 days, followed by 2 weekly vaccines (with imiquimod given before and after the vaccination), and one week of rest.  After the third cycle the patient experienced a decline in neutrophil and platelet counts, and an elevated alkaline phosphatase level.

At the end of the 3 cycles of decitabine and the vaccine, the patient had no evidence of neuroblastoma in his bone marrow aspirates and biopsies. On the one year anniversary of the patient’s last vaccination, the patient’s bone marrow continued to remain free of neuroblastoma, including clear CT scans. The decitabine/dendritic cell vaccine therapy shows some great promise and is certainly worthy of future study.  Future research in this area will involve (Krishnadas et al, 2012, p. e340):

1. Continuing this study with a larger number of patients to determine if there is a significant response rate to this therapy.

2. Examining if patients with bulky disease would also benefit from this therapy, and not just patients with a minimal disease profile.

3. Establishing a detailed understanding on how the neuroblastoma cells are being killed.

4. Determining if there are subsequent immune responses towards any disease after the vaccine treatment is completed.

 

Reference

Krishnadas, D.K., Shapiro, T. And Lucas, K. (2013). Complete Remission Following Decitabine/Dendritic Cell Vaccine for Relapsed Neuroblastoma. Pediatrics, Vol 131, No 1.

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