Phase I immunotherapy with a modified vaccinia virus (MVA) expressing human MUC1 as antigen‐specific immunotherapy in patients with MUC1‐positive advanced cancer

Abstract

The administration of TG4010 was generally well tolerated in patients with metastatic tumors, and transient disease stabilization was observed in several patients, warranting further clinical studies with the product.

Lack of Effective MUC1 Tumor Antigen-Specific Immunity in MUC1-Transgenic Mice Results from a Th/T Regulatory Cell Imbalance That Can Be Corrected by Adoptive Transfer of Wild-Type Th Cells

“…The ability to induce similarly effective immunity to MUC1 in humans could provide treatment for the majority of adenocarcinomas. Clinical trials of MUC1-based vaccines in cancer patients have so far elicited only weak CTL responses and low titer Abs of predominantly IgM isotype (15)(16)(17)(18)(19), suggesting that there is a problem in generating effective MUC1-specific T cell help. As CD8 ϩ T cells require help from CD4 ϩ T cells to establish effective CTL memory (20 -25), the lack of effective MUC1-specific Th cells in cancer patients is considered to be a major obstacle in generating effective antitumor immunity.…”

Vaccines for the Treatment of Non-Small Cell Lung Cancer: A Renewed Anticancer Strategy

“…MUC1 is a potential target for vaccine therapy because of its overexpression or aberrant glycosylation in tumors compared with normal tissue [16]. MUC1 glycoprotein has been targeted using different strategies such as dendritic cell approaches, recombinant vaccinia virus-expressing MUC1, peptide and antibody approaches, and liposomal delivery of MUC1 [17,18]. MUC1 has been found to be expressed in 60% of lung cancer cases [17].…”

“…MUC1 glycoprotein has been targeted using different strategies such as dendritic cell approaches, recombinant vaccinia virus-expressing MUC1, peptide and antibody approaches, and liposomal delivery of MUC1 [17,18]. MUC1 has been found to be expressed in 60% of lung cancer cases [17]. The extracellular core peptide of MUC1 is targeted by a liposome vaccine named L-BLP25.…”

Gene-based vaccines and immunotherapeutics

“…3). TG4010 (clinical MVA-MUC1-IL2) has shown an excellent safety profile in phase I testing and was shown to stimulate MUC1-specific T cell responses (19). It is now being tested in four phase II studies, and tolerance, in Ͼ150 patients, continues to be good.…”