The investigators' laboratory has described a new method of generating sensitized T cells for adoptive immunotherapy utilizing tumor- primed lymph node cells activated sequentially by an anti-CD3 mAb and IL-2. Exhaustive animal therapy protocols have revealed that these activated cells are capable of mediating the regression of well- established grossly visible tumor in visceral organs. Based on these preclinical studies, a clinical trial is ongoing at the University of Michigan Medical Center in which these polyclonally activated T cells are used as therapy for patients with metastatic melanoma and renal cell carcinoma. Encouraging results in the five patients treated for renal cell carcinoma, 4 responses (3 partial and 1 complete), have prompted them to initiate a new clinical trial to study the efficacy of these anti-CD3 mAb/IL-2 activated T cells in the treatment of metastatic squamous cell carcinoma (SCC) of the head and neck. This new protocol for the treatment of SCC has several aspects which make it unique and attractive for clinical investigation. While in vivo and in vitro studies have demonstrated that SCC might represent an immunogenic tumor, clinical immunotherapeutic trials of this disease are lacking. Because of SCC's presumed immunogenicity, the potential advantage that might be derived from immunotherapy may be drastic. Additionally, unlike metastatic melanoma and renal cell carcinoma, SCC tends to metastasize and recur regionally more readily facilitating clinical evaluation of observed treatment responses. The limited confines of the head and neck will also serve to facilitate cell trafficking studies as a further testament of therapeutic efficacy of this novel approach. The basic design of this therapy will be first, vaccination of patients with autologous tumor cells in the presence of the potent immune adjuvant, BCG. Lymph node cells draining the vaccination site will be surgically retrieved and activated in vitro sequentially with OKT3(anti human CD3) and IL-2. These cells will be systemically infused into patients in conjunction will IL-2 treatment to promote cell survival and function.
| Chang, Alfred E; Li, Qiao; Jiang, Guihua et al. (2003) Generation of vaccine-primed lymphocytes for the treatment of head and neck cancer. Head Neck 25:198-209 |
| Li, Q; Furman, S A; Bradford, C R et al. (1999) Expanded tumor-reactive CD4+ T-cell responses to human cancers induced by secondary anti-CD3/anti-CD28 activation. Clin Cancer Res 5:461-9 |
