Antitumor Vaccination of Patients With Glioblastoma Multiforme: A Pilot Study to Assess Feasibility, Safety, and Clinical Benefit

Abstract

Postoperative vaccination with virus-modified autologous tumor cells seems to be feasible and safe and to improve the prognosis of patients with glioblastomas. This could be substantiated by the observed antitumor immune response.

A tumor vaccine containing anti‐CD3 and anti‐CD28 bispecific antibodies triggers strong and durable antitumor activity in human lymphocytes

“…29,31 The virus-infected tumor vaccine, even without bispecific antibodies, has been shown in several clinical studies to produce a beneficial clinical response and to booster long-lived antitumor memory T cells. 3,4 Memory DTH responses could be reactivated with ATV-NDV vaccine many times, 5 thus indicating that no depletion of antitumor reactive T cells had occurred. We have postulated that the addition of danger signals through doublestranded RNA (dsRNA) 32 and cell surface-expressed HN proteins 10 can overcome T-cell unresponsiveness.…”

“…[1][2][3][4][5] These Phase I/II studies included primary operated breast carcinoma, 1 glioblastoma 3 and squamous cell carcinoma of the head and neck (HNSCC). 4 Infection of tumor cells with Newcastle Disease Virus (NDV) was shown to introduce into the tumor cells danger signals 6 by way of double-stranded RNA 7,8 and T-cell costimulatory activity 9 via the viral cell surface-expressed hemagglutinin-neuraminidase (HN) protein.…”

Recombinant Newcastle disease virus (NDV) with inserted gene coding for GM-CSF as a new vector for cancer immunogene therapy

“…2,12 Recently, we reported results from two non-randomized phase II studies, which aimed at feasibility, safety and clinical benefit. In both studies (glioblastoma multiforme (GBM) 13 and head and neck carcinoma (HNSCC) 14 ), the establishment of primary tumor cell cultures was feasible and successful in about 80-90%. All tumor cells tested could be successfully infected by NDV and showed cell surface expression of MHC I and viral HN molecules.…”

“…All tumor cells tested could be successfully infected by NDV and showed cell surface expression of MHC I and viral HN molecules. Clinical benefits in GBM included one complete remission and prolongation of median overall-survival (100 weeks versus 49 weeks in controls 13 ). Clinical benefits in the HNSCC study included improvement of the 5-year survival rate in stage III and IV (61 versus 38%).…”

Danger signals in tumor cells: a risk factor for autoimmune disease?

“…Clinical evaluation of this vaccine revealed prolonged survival in a number of prospective studies with different types of cancer (reviewed in [18]) and in a randomized controlled trial in colon cancer [19]. The ATV-NDV vaccine showed a high safety profile and did not induce autoimmune phenomena such as vasculitis, rheumatoid arthritis or lymphatic disorders [19][20][21][22]. A detailed description of the mechanisms of action of this vaccine, in which the production of IFN-a plays a key role, was reviewed recently [18].…”