title: Trial Watch: Therapeutic vaccines in metastatic renal cell carcinoma.
abstract: Despite the renaissance of cancer immunotherapy, no novel immunotherapy has been approved for the treatment of renal cell cancer (RCC) since the availability of recombinant cytokines (interleukin-2, interferon-α). All vaccine trials have failed to meet their endpoints although they have highlighted potential predictive biomarkers (e.g., pre-existing immune response, hematological parameters, tumor burden). Recent advances in immunomodulatory therapies have prompted the study of combination treatments targeting the tumor immunosuppressive microenvironment consisting of regulatory T-cells (Treg), myeloid suppressor cells, and cytokines. Approaches under investigation are use of inhibitors to curb the overexpression of immune checkpoint ligands by tumor cells (e.g., anti-CTLA-4, anti-PD-1/PD-L1) and exploiting the immunomodulatory effects of anti-angiogenic agents that are the current standard of metastatic RCC care. Phase III trials are focusing on the possible synergy between therapeutic vaccines (e.g., IMA-901 and AGS-003) and anti-angiogenic agents.
authors.affiliation: Department of Medical Oncology; Hôpital Européen Georges Pompidou (AP-HP) ; Paris, France ; INSERM; PARCC (Paris Cardiovascular Research Center); Université Paris Descartes - Sorbonne Paris Cité ; Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Combe
authors.affiliation: Department of Medical Oncology; Hôpital Européen Georges Pompidou (AP-HP) ; Paris, France ; INSERM; PARCC (Paris Cardiovascular Research Center); Université Paris Descartes - Sorbonne Paris Cité ; Paris, France.
authors.forename: Eleonore
authors.initials: E
authors.lastname: de Guillebon
authors.affiliation: Department of Medical Oncology; Hôpital Européen Georges Pompidou (AP-HP) ; Paris, France.
authors.forename: Constance
authors.initials: C
authors.lastname: Thibault
authors.affiliation: INSERM; PARCC (Paris Cardiovascular Research Center); Université Paris Descartes - Sorbonne Paris Cité ; Paris, France ; Department of Biological Immunology; Hôpital Européen Georges-Pompidou (AP-HP) ; Paris, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Granier
authors.affiliation: INSERM; PARCC (Paris Cardiovascular Research Center); Université Paris Descartes - Sorbonne Paris Cité ; Paris, France ; Department of Biological Immunology; Hôpital Européen Georges-Pompidou (AP-HP) ; Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Tartour
authors.affiliation: Department of Medical Oncology; Hôpital Européen Georges Pompidou (AP-HP) ; Paris, France ; INSERM; PARCC (Paris Cardiovascular Research Center); Université Paris Descartes - Sorbonne Paris Cité ; Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Oudard
keywords: AGS-003; CAIX; IMA-901; Memorial Sloan Kettering Cancer Center; NK; Von Hippel Landau; anti-angiogenic agent; carbonic anhydrase IX; ccRCC; checkpoint inhibitor; clear cell renal cell carcinoma; CIK; cytokine induced killer; CTL; cytotoxic T-lymphocyte-associated protein 4; DC; cytotoxic T-lymphocyte; CTLA-4 ; dendritic cell; GM-CSF; granulocyte macrophage colony-stimulating factor; HGF; heat shock protein; IFN; hepatocyte growth factor; HLA; human leukocyte antigen; HSP; interferon; IL; interleukin; KIR; killer immunoglobin-like receptor; MDR; major histocompatibility complex; MSKCC; multidrug resistance protein; MDSC; myeloid derived suppressor cell; MHC; natural killer; ORR; overall response rate; OS; peripheral blood mononuclear cell; PD-1; phosphatase and tensin homolog; TAA; programmed cell death ligand 1; PTEN; programmed cell death protein 1; PD-L1; regulatory T-cell; TUMAP; renal cell carcinoma; therapeutic vaccine; toll-like receptor; Treg; tumor infiltrating lymphocyte; TLR; tumor-associated antigen; TIL; tumor-associated peptide; VEGF; vascular endothelial growth factor; VHL; verall survival; PBMC