Adenovector engineered interleukin-2 expressing autologous plasma cell vaccination after high-dose chemotherapy for multiple myeloma - a phase 1 study

Abstract

Eight multiple myeloma patients participated in a phase I trial evaluating the feasibility and safety of subcutaneous vaccination with adenovirus engineered, autologous plasma cells after high-dose therapy. Plasma cells were concentrated from bone marrow harvests by negative selection and high gradient magnetic separation. The mean plasma cell yield was 2.61 × 10

Decreased tumorigenic potential of EphA2-overexpressing breast cancer cells following treatment with adenoviral vectors that express EphrinA1

“…[17][18][19][20] The results of animal studies and clinical trials in humans for cancer therapy have further increased interest in adenoviral-based therapy. [21][22][23][24][25][26] Based on the differential ligand binding that EphA2 demonstrates in normal versus malignant cells, we describe herein the engineering of HAd type 5 (HAd5) vectors that express secreted forms of EphrinA1 and show that these vectors can negatively regulate tumor cell growth in vitro and in vivo.…”

Adenovirus-mediated intralesional interferon-γ gene transfer induces tumor regressions in cutaneous lymphomas

“…[23][24][25][26] CD8 ϩ CTL-mediated tumorcell lysis is achieved, ie, through exocytosis of granules containing cytotoxic protein TIA-1. Following injection with adenovirusengineered IL-2-expressing autologous plasma cells, Trudel et al 27 reported the induction of local inflammatory response consisting predominantly of CD8 ϩ and/or TIA-1 ϩ T cells as well. Real-time PCR demonstrated decrease in CD4/CD8 ratio in 6 of 8 patients following TG1042 injections, confirming once again the increase in CD8 ϩ cells.…”

Immunotherapy of metastatic melanoma by intratumoral injections of Vero cells producing human IL-2: Phase II randomized study comparing two dose levels

“…However, the efficacy of this approach in treating established tumors has been shown in only a few animal models. 7,8 Nevertheless, clinical studies were initiated on the basis of this rationale, and vaccination with cytokine gene -transduced autologous or allogeneic tumor cells was carried out in patients with melanoma, 14 -17 neuroblastoma, 18 -20 renal cell cancer, 21 prostate carcinoma, 22 multiple myeloma, 23 glioma, 24,25 and colorectal cancer. 26 In these protocols, only 20-30% of patients developed a T cell -specific antitumor response, and only a minority of patients ( < 10% ) had a clinical minor or partial response (reviewed in Ref.…”