Dendritic Cell Vaccine trial for Malignant Astrocytoma: potential interaction with adjuvant Chemotherapy

human brain

Clinical study on Malignant Astrocytoma

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Summary

Dendritic cell vaccination has been applied to the treatment of a variety of cancers, including malignant astrocytoma. In this study, 13 patients with malignant astrocytoma using dendritic cell vaccination were treated and have shown that this treatment is safe and is likely to be effective in combination with standard adjuvant therapy. The results of this trial show that Dendritic Cell Vaccines significantly enhance the response to adjuvant Chemotherapy and that they have significant potential in the treatment of this disease.

Introduction

This study involved 13 patients in total (9 patients with Glioblastoma Multiforme and 4 patients with Anaplastic Astrocytoma). The scope was to test the interaction of DCT with adjuvant Chemotherapy in patients with Malignant Astrocytoma.

• Patients with grade III malignant astrocytoma ages 1-75 years old
• Absence of concurrent infectious disease
• Normal haematological parameters, absence of autoimmune disease or other significant neoplasms and absence of pregnancy
• 13 patients were enrolled in this trial
o 9 patients with Glioblastoma Multiforme
o 4 patients with Anaplastic Astrocytoma

Methodology

• 450mL peripheral blood was taken by venous puncture into a blood bag containing anticoagulant, diluted to 1:2 Buffered salt solution HBSS and transferred into 50mL tubes underlayed with Ficoll-paque and centrifuged to obtain PBMCs.
• PBMCs were washed twice with HBSS, resuspended at 107 cells/mL in 1% plasma/RPMI1640 and incubated for 60 minutes at 37oC
• The adherent fraction cultured with rhGM-CSF and rhIL-4 with 1%autologous plasma RPMI1640 for 6 days

Treatment

All DCV contains 106 cells given Intradermally (ID) into a single site on the abdomen; 6 injections at 2-weekly intervals.

Results

A systemic review of all published clinical trials to document the proportion of patients who had an objective response as defined by WHO criteria or by the Response Evaluation Criteria in Solid Tumors (RECIST) after dendritic cell vaccination in melanoma, prostate cancer, malignant glioma and renal cell carcinoma. From this review, it concludes that the clinical benefit of dendritic cell- based immunotherapy is terms of objective response is real, but small. With 8.5% of melanoma patients achieving an objective response, 7.1% of patients with prostate cancer, 15.6% of patients with malignant glioma and 11.5% of patients with advanced renal cell carcinoma.

Survival Benefit

• 3 patients with anaplastic astrocytoma received Chemotherapy as Pre-vaccination treatment and Post-vaccination treatment
o 1 patient exhibit complete response (CR) for 25 months
o 1 patient exhibits Partial Response (PR) for 16 months
o 1 patient had progressive disease

• 1 patient with anaplastic astrocytoma received Chemotherapy as Post-vaccine treatment only which achieved Partial Response (PR) for 20 months.
• 9 of 13 patients survived for 9 months, 6 of 13 survived for 12 months and 3 of 13 patients for 18 months or longer

Conclusion

Dendritic Cell Vaccine significantly enhances the response to adjuvant Chemotherapy and that it has significant potential in the treatment of this disease.

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Scientific article publishing date : 25/8/2007

Immucura identifier : BSC21_003EN

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