Over the past several years, the dominant paradigm in
drug development for metastatic
renal cell carcinoma (mRCC) has been to more selectively and potently target moieties such as the
vascular endothelial growth factor receptor. The effectiveness of this strategy appears to be nearing a plateau, however, underscoring the need for novel approaches.
Vaccine-based
therapies represent one such approach. Several distinct
vaccines are currently being examined in mRCC, each using a distinct mechanism of action. For instance, the autologous dendritic cell
vaccine AGS-003 uses patient-specific
antigens derived from primary
tumor tissue. In contrast, the poxvirus
vaccine TG4010 produces an antigenic response to MUC1, a
cell surface glycoprotein that reduces cell-cell interactions and thereby precludes contact inhibition. Other
vaccines elicit a response to a broader spectrum of
antigens-for instance, the
vaccine IMA901 is based on 9
tumor-associated
peptides identified from a novel biotechnology platform combining mass spectroscopy, microarray analysis of
RNA expression, and immunogenicity assays. Herein, the current status of
vaccine-based
therapies for mRCC is described in detail. Furthermore, challenges to clinical implementation (eg, cost, optimal pairing with targeted agents, appropriate sequencing) are presented.