Autologous antigen-loaded vaccine safe, feasible for neuroblastoma
NATIONAL HARBOR, Md. — An investigational vaccine of autologous dendritic cells loaded with autologous tumor antigens was safe and feasible as an adjuvant therapy when given after standard care therapies for glioblastoma, according to phase 2 trial results presented at the Society for Immunotherapy of Cancer Annual Meeting.
The investigators were able to manufacture a successful apheresis product for subsequent infusion in all but one patient, and no patients experienced treatment-related toxicities.
“There is an unmet need for new and effective treatments that can be added to standard care for glioblastoma in the hope of improving survival,” Robert O. Dillman, MD, chief medical officer for AiVita Biomedical and one of the study co-authors, told Cell Therapy Next.
AV-GBM-1 (AiVita Biomedical) is an autologous patient-specific dendritic cell vaccine that is given as adjuvant therapy after standard care therapy for glioblastoma, which may include surgical resection followed by the combination of radiotherapy and temozolomide (Temodar; Merck).
The use of patient-specific vaccines consisting of autologous dendritic cells loaded with autologous tumor associated antigens derived from a short-term cell line of self-renewing autologous tumor cells is a novel approach in the treatment of glioblastoma, Dillman said.
The patient-specific vaccine approach, although logistically complex, is a feasible one according to Dillman. The vaccine product is manufactured while the patient is being treated with post-surgical temozolomide and radiotherapy. Injections of AV-GBM-1 are given after the patient begins recovering from chemo- and radiotherapy and remains timely for the treatment of glioblastoma.
Patients aged 70 years or younger were eligible for the study if the investigators determined the successful establishment of a short-term cancer cell line and if the patient was able to undergo successful leukapheresis collection of monocytes.
Samples from the patient’s tumor were collected at the time of surgery and used to create a short-term cell line, whereas dendritic cells were produced by incubating peripheral blood myocytes with interleukin-4 and granulocyte-macrophage colony-stimulating factor. Patients were given three weekly subcutaneous injections of the vaccine one week after completion of their chemotherapy and radiotherapy regimen. Additional doses were provided at weeks 8, 12, 16, 20 and 24, for a total of 8 doses.
The study’s primary objective was a 50% decrease in death at 15 months after study enrollment.
The study results showed the successful creation of a cell line in 46 of 48 glioblastoma samples. The investigators were able to obtain a satisfactory leukapheresis product in 41 of 42 patients, after repeating the process for nine patients.
Thirty of 55 planned patients have been enrolled in the intent-to-treat portion of the trial, with 29 patients having started treatment.
Three patients have completed all eight doses of AV-GBM-1 and three patients had to discontinue study treatment due to disease progression. There are currently 18 patients receiving treatment with AV-GBM-1, with 121 doses having been administered.
Proteomic analysis of blood samples taken at baseline and during each vaccine injection has shown an immune response in seven of eight patients.
No patients experienced treatment-related toxicity.
Dillman said the patient-specific vaccine approach is feasible, as this study demonstrated the ability to manufacture the product in a timely fashion for nearly every patient.
“We are happy to see that the 6-month survival rate is 96%, and the 1-year survival rate is 91%,” he said, but cautioned that these are early data at a time when the trial has not yet completed its enrollment and the longest follow-up is only 12 months for three patients.
“If improved survival with safety persists,” he added, “then this could eventually become part of standard care if proven in a phase 3 randomized trial.” – by Drew Amorosi
Bota, et al. Abstract O22. Presented at: Society for Immunotherapy of Cancer Annual Meeting; Nov. 7-10, 2019; National Harbor, MD.
Disclosure: Dillman is the chief medical officer for AiVita Biomedical.