ABSTRACT
The authors report the results of a phase I clinical study using semiallogeneic cancer vaccines formulated with granulocyte-macrophage colony-stimulating factor (GM-CSF) to treat patients with metastatic adenocarcinomas of the gastrointestinal tract. A specially engineered cell line, FO1-12, was used to generate semiallogeneic hybrids by fusion with patient-derived tumor cells; the hybrids express HLA class I and II haplotypes derived from both parental cells. For treatment, the vaccine was mixed with GM-CSF, irradiated, and injected intradermally into patients at weekly or biweekly intervals. Vaccinations were associated with minimal or no toxicity and showed that semiallogeneic hybrids formulated with GM-CSF can induce a specific antitumor immune response in some patients, as measured by a delayed-type hypersensitivity response to autologous tumor cells. Because of the simplicity, feasibility, and flexibility of this immunotherapeutic approach, semiallogeneic hybrid vaccines have the potential to be used in the treatment of virtually any type of cancer.
Subject(s)
Adenocarcinoma/secondary , Adenocarcinoma/therapy , Cancer Vaccines/therapeutic use , Gastrointestinal Neoplasms/therapy , Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use , Adenocarcinoma/immunology , Adult , Aged , Aged, 80 and over , Cancer Vaccines/adverse effects , Cancer Vaccines/genetics , Female , Gastrointestinal Neoplasms/immunology , Granulocyte-Macrophage Colony-Stimulating Factor/adverse effects , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Humans , Hybrid Cells/metabolism , Hybrid Cells/transplantation , Immunotherapy, Adoptive/methods , Male , Middle Aged , Pilot Projects , Tumor Cells, Cultured/metabolism , Tumor Cells, Cultured/transplantation , Vaccines, Synthetic/adverse effects , Vaccines, Synthetic/genetics , Vaccines, Synthetic/therapeutic useABSTRACT
Bladder cancer is the fourth most commonly diagnosed malignancy in men and the eighth most common in women. It represents a spectrum of disease, ranging from superficial, well-differentiated disease, which does not significantly impact survival, to highly malignant tumors for which long term survival may be dismal. Transitional-cell carcinoma, which constitutes the vast majority of bladder cancers in the United States, may develop as carcinoma in situ or as invasive carcinoma. This article focuses on transitional-cell carcinoma with a review of the major aspects of the disease, including the epidemiology, diagnosis and staging, and management (including organ preservation). Therapeutic options are explored, including surgery, radiotherapy, chemotherapy, and combined modality therapy.
