Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
Immunotherapy with tumor vaccines in renal cancer (Meeting abstract).
Ann Oncol; 7(Suppl 1):18 1996. Unique Identifier : AIDSLINE ICDB/98625860 Pardoll DM; John Hopkins University School of Medicine, Baltimore, MD
Abstract:
There is mounting evidence that many if not all tumors possess antigens capable of being recognized by T cells. Over the past few years, our group has been analyzing the immune response induced by immunization with tumors engineered to secrete cytokines locally. In a study comparing multiple different cytokine genes, GM-CSF stood out as the most effective in inducing systemic immune responses against the poorly immunogenic F10 variant of B16 melanoma as well as 5 other murine tumors. The systemic immune response generated by immunization with GM-CSF transduced tumor cells was found to be dependent both on CD4+ T cells and CD8+ T cells. Despite the fact that CD8+ tumor specific T cells were generated by this immunization scheme, the rejection of MHC class I+ challenge tumors did not require that the immunizing tumor express MHC class I molecules on its surface. Taken together, these findings suggest that immunization with GM-CSF transduced tumor cells alters the presentation of tumor specific antigens such that powerful antigen presenting cells are brought to the tumor site which process and present both MHC class I and MHC class II-restricted antigens. Phase I trials in patients with Stage IV kidney cancer demonstrated that GM-CSF transduced vaccines produced enhanced immune responses specific for normal renal antigens. Generation of CD8+ tumor specific T cells by this immunization strategy has allowed us to analyze the complexity of tumor specific peptides recognized by the CTL population. In one colon tumor there was a single predominant tumor specific peptide identified which was derived from the envelope gene of an endogenous C-type provirus. Clinical trials in patients with Stage IV renal cancer comparing GM-CSF gene transduced autologous vaccines vs non-transduced vaccines demonstrated the generation of enhanced antitumor immune responses as well as induction of regression of metastases in a patient treated at the highest dose level of GM-CSF transduced cells.
Keywords: Antibody Formation CD4-Positive T-Lymphocytes/IMMUNOLOGY CD8-Positive T-Lymphocytes/IMMUNOLOGY Cancer Vaccines/IMMUNOLOGY/*THERAPEUTIC USE Clinical Trials, Phase I Colonic Neoplasms/THERAPY Granulocyte-Macrophage Colony-Stimulating Factor/*GENETICS/ IMMUNOLOGY Human Kidney Neoplasms/IMMUNOLOGY/*THERAPY Neoplasm Staging ABSTRACT 980228
M9820770
AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
