Preliminary Analysis of Patients With Progressive Renal Cell Carcinoma Vaccinated With CA9-peptide–Pulsed Mature Dendritic Cells

Abstract

Carbonic anhydrase-IXG250/MN (CA9) is a renal cell carcinoma (RCC)-associated antigen ubiquitously expressed in the clear-cell subtype of RCC. Two CA9-derived peptides have been identified defining a cytotoxic T-lymphocyte epitope and human leukocyte antigen (HLA)-DR epitope, able to induce T-cell responses in vitro. A phase I clinical trial was performed with CA9-peptide-loaded dendritic cells (DCs) in patients with progressive, cytokine-refractory metastatic RCC to assess the safety, toxicity, and induction of CA9-specific immunity. Patients with objective progressive metastatic RCC received 5 vaccinations of mature DCs pulsed with the CA9-derived peptides and keyhole limpet hemocyanine (KLH). Peripheral blood was collected at regular intervals, delayed-type hypersensitivity (DTH) was tested at baseline and after the last vaccination, and skin biopsies of positive DTH sites were collected for immunomonitoring purposes. Patients were also monitored for clinical responses. No significant toxicity was observed. All patients developed humoral responses against KLH, and demonstrated DTH conversion. Evaluation of biopsy material suggested an increased influx of T-helper cells. In none of the immunomonitoring assays was evidence for the induction of CA9-peptide-specific immunity observed. No clinical responses were observed. The vaccination of DCs pulsed with KLH and 2 CA9-derived peptides was well tolerated. The lack of induction of CA9-peptide-specific immune responses indicates that this particular vaccine regimen is poor in inducing CA9-peptide-specific immune responses.

The tumor antigens RHAMM and G250/CAIX are expressed in head and neck squamous cell carcinomas and elicit specific CD8+ T cell responses

“…Furthermore, HLA-A * 0201 restricted T cell epitopes derived from G250/CAIX were identified, eliciting peptide-specific CTLs both in vitro and in vivo (19,48). Clinical phase I/II vaccination trials with G250/CAIX-derived peptides for patients with advanced renal cell carcinoma revealed to be safe and feasible with no gastrointestinal hepatic toxicity observed despite CAIX expression in large bile duct epithelium and gastric mucosal cells (49,50). In the study of Uemura et al, most of the patients developed peptide specific CTLs and/or immunoglobulin G reactive to the peptides and showed clinical responses (49).…”

Spontaneous Peripheral T-cell Responses toward the Tumor-Associated Antigen Cyclin D1 in Patients with Clear Cell Renal Cell Carcinoma

“…We observed an overexpression of CA-IX in all but one ccRCC samples. CA-IX has been identified as a therapeutic target for RCC (13,28,29), and evaluated in clinical studies (30)(31)(32), but it has not yet induced strong antitumor immune responses. In addition to CA-IX, ADFP, Cyclin D1, C-MET, and RGS-5 are also overexpressed in ccRCC (14).…”

Immunotherapy of Lung Adenocarcinoma Patient with Peptide-Pulsed Dendritic Cells: a Case Report

“…In the previous studies, lysates or apoptotic bodies of tumour cells were used for DCs stimulation (Dubsky et al 2005;Nencioni et al 2008). Recently, the synthetic oligopeptide (9-12 amino acids) with epitopes of well-defined tumour antigens are widely used in immunotherapy (Bleumer et al 2007). In non-small cell lung cancer (NSCLC), MUC-1 and MAGE-A3 antigens are frequently used for both ex vivo DCs loading (adoptive immunotherapy) as well as for active immunotherapy (antigenic vaccine) (Bradbury and Shepherd 2008;Romero 2008).…”