Immunizing Patients With Metastatic Melanoma Using Recombinant Adenoviruses Encoding MART-1 or gp100 Melanoma Antigens

Abstract

Background: The characterization of the genes encoding melanoma-associated antigens MART-1 or gp100, recognized by T cells, has opened new possibilities for the development of immunization strategies for patients with metastatic melanoma. With the use of recombinant adenoviruses expressing either MART-1 or gp100 to immunize patients with metastatic melanoma, we evaluated the safety, immunologic, and potential therapeutic aspects of these immunizations.

Biased epitope selection by recombinant vaccinia-virus (rVV)-infected mature or immature dendritic cells

“…39 Thus, various strategies have been suggested to cause expression of whole Ag in vivo with the purpose of priming polyvalent CD8+ T-cell/HLA-class I-restricted and CD4+ T-cell /HLA-class II-restricted immune responses. These strategies include administration of expression vectors, 40,41 naked DNA, 42,43 chaperon delivery systems such as autologous heat-shock proteins, 44 pools of unselected protein extracts such as tumor lysates, 45 or whole proteins. 46 An appealing tactic for Ag delivery includes the induction of Ag expression in DC to combine the pluripotentiality of whole Ag delivery with the costimulatory properties of these professional antigen-presenting cells.…”

Lymphotactin cotransfection enhances the therapeutic efficacy of dendritic cells genetically modified with melanoma antigen gp100

“…Lastly, DC can express tumor antigens continuously and MHC-peptide complexes for long periods. 6,10 Nevertheless, the antitumor immunity induced by TAA gene-modified DC vaccine is still limited in clinical trials, 11,12 suggesting that DC-based vaccine will need to be modified to improve the efficacy before being widely used. So, the primary aim of our present study is to enhance the therapeutic efficacy of DC-based vaccine by genetic modification of DC.…”

Prostate cancer: genes, environment, immunity and the use of immunotherapy

“…However, use of a recombinant adenoviral vector to deliver the antigen has shown remarkable effects through the generation of antigenspecific immune response and strong antitumor immunity. [59][60][61][62] Immunotherapeutic studies for prostate cancer were initiated using the peptides from PSA, PAP or PSMA (prostate-specific genes) to generate antigen-specific CTL responses to destroy antigen-bearing tumor cells. There are several limitations related to peptide-based immunization approaches, one being that in vivo tumors may have several relevant epitopes to T cells, and hence a single epitope might not be sufficient to induce the required protective immunity.…”