Research Report 2012
In May 2012 CIKA received a funding outcomes report for the period 1 July 2010 to 31 December 2011 in respect of the funding committed to the Murdoch Children’s Research Institute in support of the dendritic cell vaccine project. Project team members Yosuke Minoda, Dylan King and Denise Caruso reported as follows.
Despite the progress over the last several decades in paediatric cancer, further investigations are required for solid tumour patients who fail current standards of care. The goal is to develop a novel therapy that is more effective at targeting the tumour while reducing severe side affect which is one of the major issue of the current cancer therapy.
Since conventional treatments have shown minimal clinical responses for patients with stage 4 disease, a phase 1 clinical trial using dendritic cell (DC) immunotherapy was conducted. Past studies have shown that the DC immunotherapy can potentially be an effective form of treatment against cancer. Unlike other types of cancer, past studies have indicated that neuroblastoma cells expresses the major histocompatibility complex I making DC therapy an attractive prospect
The primary objective of the study is to assess feasibility and safety for the administration of the autologous dendritic cells pulsed with tumour lysates. Secondary objectives will investigate anti-tumour responses:
1) the clinical level of response using traditional measures;
2) the immunological level of response by measuring cell mediated and humoural responses. These include: key cytokine activity, key phenotypical expressions of patient’s dendritic cells and patient’s capacity to produce anti-tumour antibody before and after the treatment.
Description of Program Progress in Current Period
1) 2008 to 2011, we recruited patients and prepared dendritic cell anti-tumour vaccines tailored made using patient’s cells (refer to method).
2) We conducted post trial analysis since late 2010 through to present to investigate if vaccines had any clinical response.
3) 2011 – La trobe University honours student have participated for one year investigating cytokine profile of enrolled patients before and after the treatment with vaccines.
4) Late 2011 to present, anti-tumour ELISA assay was prepared to determine patient’s capacity to produce antibody against their own tumour before and after the treatment with vaccines.
We are currently preparing the manuscript for publication. The trial is now closed. All of the remaining clinical samples will be stored according to the RCH ethics until permission is given for the samples to be destroyed.
1) No patients had a vaccine related toxicity issues.
2) Four out of ten patients treated had a complete response during the trial period.
3) Three of four patients with complete response were alive with stable disease at 41, 31 and 24 months follow up.
4) No vaccines have failed quality test with no contamination for the vaccines produced by staff.
5) Primary aims of the trial to prove safety and feasibility were achieved
Cancer therapy today heavily involves radiation therapy and chemotherapy, both of which lack capacity to specifically target tumour without inducing side effects. This can have a negative impact both mentally and physically. For this reason, an antitumour vaccine study was conducted with an aim to determine if this immunotherapy can be safely administered to paediatric patients with no harmful effects while show signs of positive clinical response.
Technically, the project showed many positives as sufficient amount of tumour lysate was produced from small quantity of tumour tissues available and each vaccine produced showed negative for contamination meaning that vaccine was produced very effectively with good standard of quality.
Furthermore, both leukapheresis products and fresh blood collected after mobilizing with G-CSF have shown capacity to produce mature dendritic cells from isolated monocytes. Since drawing blood from patient without using leukapheresis is physically less stressful, this is great for paediatric patients as they can have flexibility in method of producing dendritic cell vaccines. However, use of fresh blood can be more challenging technically as number of white blood cells available for vaccine process is lower compared to leukapheresis products. This problem can be resolved by increasing the number of occasions when blood is collected from patients.
The study achieved the primary aim of demonstrating safety and feasibility with none of the patients having any toxicity related issues. Furthermore all attempts to produce vaccines for enrolled patients were successful. 9 out of 10 treated patients showed stable disease or better over the trial period and in short term follow up. 3 of 4 patients with complete response have managed to stay disease free over the follow up at 41, 31 and 24 months.
Thus this trial was a successful study that demonstrated that autologous tumour lysate pulsed dendritic cell anti-tumour vaccine is well tolerated and has a great potential to become an important part of cancer therapy for children with advanced solid tumours.
Dendritic cell anti-tumour vaccine therapy for neuroblastoma, brain tumour and recurring solid tumour paediatric patients have, overall, responded positively with no major toxicity and good clinical response. The Tumour Immunology group has made a significant contribution to the field of cancer immunotherapy in particular, paediatric oncology. Whilst these accomplishments are noteworthy, the real impact of this work being done at the CCC at the RCH is for the patients themselves who would otherwise have had no other treatment options.
We are optimistic that immunotherapy against cancer will become part of a standard therapy in the near future and this will give potential opportunity for kids with cancer to have a relatively normal life as their hospital admission time for treatment will be significantly cut down.
Murdoch Childrens Research Institute would like to thank CIKA for being the main driver behind raising the vital funds to support this work. We would also like to thank Children’s Cancer Center Foundation for their support to conduct this study.