The adoptive transfer of ex vivo activated T lymphocytes derived from lymph nodes (LNs) draining autologous tumor cell vaccines had very low toxicity and mediated tumor regression in some adult patients with malignant gliomas or renal cell carcinoma treated on our previous clinical studies. The first objective of this research-driven proposal is to determine the feasibility and toxicity of adoptive immunotherapy in pediatric patients with recurrent solid tumors with emphasis on brain tumors. Short-term autologous tumor cell lines will be established at the time of surgical resection. A vaccine consisting of irradiated autologous tumor cells admixed with GM-CSF will be injected intradermally to stimulate an immune response in draining LNs. The hyperplastic draining LNs will be surgically removed and the T cells will be activated ex vivo with staphylococcal enterotoxin A (SEA) and IL-2 to induce differentiation to effector function and rapid proliferation. Activated T cells will be harvested at the peak of the proliferative response and administered intravenously to patients. Toxicity and response will be measured. The second objective is to analyze the T cell and serologic response to autologous tumor antigens (Ags). The precursor frequency of CD4+ and CD8+ T cells that respond to tumor lysate presented by dendritic cells (DC) will be determined in the vaccine-draining LN and compared with pre and post treatment PBMC. The third objective will explore a basic question in tumor immunology, namely, whether immunodominant T cell responses are cross-reactive with antigens present in allogeneic tumors of similar histologic type. Vaccine-draining LN T cells that respond to autologous tumor lysate will be stimulated using autologous DC pulsed with lysate derived from allogeneic glioma lines. If cross-reactivity is not observed it would indicate that private tumor antigens are immunodominant in this vaccination method and support the strategy of autologous tumor vaccines. Alternatively if cross -reactive glioma Ags are identified it would stimulate future studies for molecular characterization of the antigens and provide the rationale for development of a uniform glioma vaccine.
| Wang, Li-Xin; Shu, Suyu; Disis, Mary L et al. (2007) Adoptive transfer of tumor-primed, in vitro-activated, CD4+ T effector cells (TEs) combined with CD8+ TEs provides intratumoral TE proliferation and synergistic antitumor response. Blood 109:4865-76 |
| Wang, Li-Xin; Shu, Suyu; Plautz, Gregory E (2005) Host lymphodepletion augments T cell adoptive immunotherapy through enhanced intratumoral proliferation of effector cells. Cancer Res 65:9547-54 |
| Kjaergaard, Jorgen; Wang, Li-Xin; Kuriyama, Hideyuki et al. (2005) Active immunotherapy for advanced intracranial murine tumors by using dendritic cell-tumor cell fusion vaccines. J Neurosurg 103:156-64 |
| Wang, Li-Xin; Kjaergaard, Jorgen; Cohen, Peter A et al. (2004) Memory T cells originate from adoptively transferred effectors and reconstituting host cells after sequential lymphodepletion and adoptive immunotherapy. J Immunol 172:3462-8 |
