Neuroblastoma is the most common extra-cranial solid tumor in children, with two thirds of patients presenting with advanced disease. The long-term survival for the advanced stages after infancy remains poor, despite aggressive therapy including bone marrow transplant. Alternative therapeutic approaches are urgently needed. In this application, the applicant plans to explore the role of active immunotherapy with an anti-Id vaccine, Mab 1A7, directed against anti-GD2 in neuroblastoma. The choice of GD2 antigen as the target of immunotherapy is based on the promising results obtained by the applicant and others using anti-GD2 Mabs for passive immunotherapy of neuroblastoma. Preclinical studies of Mab 1A7 demonstrated the generation of an antitumor antibody response in syngeneic mice, rabbits, and cynomolgus monkeys. Preliminary results from an ongoing phase I trial of Mab 1A7 mixed with the adjuvant QS-21 in melanoma patients have shown that such immunotherapy is well-tolerated and can induce immune response. Thus, the applicant proposes to conduct a pilot study using Mab 1A7 + QS21 as a tumor vaccine for treatment of advanced stage neuroblastoma. In addition, the applicant plans to explore the use of GM-CSF as an adjuvant for anti-Id based cancer vaccine.
The specific aims are as follows: 1) To assess the frequency of immune responses to the anti-Id vaccine +/- GM-CSF. Both humoral and cell-mediated immune responses will be determined. 2) To evaluate the toxicities of anti-Id vaccine therapy +/- GM-CSF. 3) To describe the clinical efficacy of anti-Id vaccine therapy +/- GM-CSF in advanced stage neuroblastoma and the correlation with immune responses. These undertakings should yield useful information on the safety of the anti-Id based tumor vaccine and its effectiveness in inducing immune response in neuroblastoma. It should also provide preliminary data on the clinical efficacy of such vaccine and the potential of GM-CSF as an adjuvant for anti-Id based tumor vaccine and shed light on the therapeutic potential of such an approach in other GD2(+) tumors, such as small cell lung cancer, melanoma and some sarcomas.
| Omura-Minamisawa, M; Diccianni, M B; Chang, R C et al. (2001) p16/p14(ARF) cell cycle regulatory pathways in primary neuroblastoma: p16 expression is associated with advanced stage disease. Clin Cancer Res 7:3481-90 |
