Neuroblastoma, the most common extracranial solid tumor of childhood affects approximately 500 children a year in the United States. When the tumor occurs in infants (children <1 yr), it is frequently localized and responds well to therapy. Even disseminated disease can be eradicated in about 75% of infants and may undergo spontaneous remission. In older children (>1 yr), the prognosis is far worse. Although patients with localized disease may still be cured by conventional therapy, 80% or more of those with disseminated tumor can be expected to relapse within 3 years, and virtually none of this subgroup will become long-term survivors. Although remission rates have increased over the past decade, there is no evidence of significant improvement in long-term survival. In the current protocol, we will learn whether cells genetically modified to secrete the T cell chemokine Lymphotactin (Lptn) can be given safely and whether they will enhance the anti-tumor immunity induced by IL-2 transduced cells. We have chosen this combination of chemokines and cytokines since they enhance discrete phases of the immune response, and data from our murine models has shown that they act in concert to augment induction of an anti-tumor immune response. Because Lptn attracts T lymphocytes to the intended site of T cell antigen interaction, the molecule is particularly suited to the persistent local delivery that will occur with injected transduced tumor cells, rather than the more widespread, transient expression that occurs with injection of the molecule itself.
Showing the most recent 10 out of 459 publications
