Th2-dominated antitumor immunity induced by DNA immunization with the genes coding for a basal core peptide PDTRP and GM-CSF

Abstract

Our previous study showed that DNA vaccination with a plasmid vector encoding a core peptide of mucin1 (PDTRP) provided modest protection against challenge with tumor cells that expressed mucin1 protein. We report here that a DNA vaccine comprising a modified PDTRP plasmid and GM-CSF coding sequence at the C-terminus induced better protection against tumor challenge. The increased protection was directly correlated with a stronger PDTRP-specific immune response induced by the GM-CSF fusion plasmid. The plasmid encoding GM-CSF and the target PDTRP antigen induced a greater PDTRP-specific Th proliferation, antibodies, and cytotoxicity. Interestingly, the modified plasmid vaccine predominantely enhanced the type 2 immune responses manifested by an increased IgG1 to IgG2a antibody ratio and a greater induction of GATA-3 and IL-4 mRNA than that of T-bet and IFN-g mRNA in spleen cells from vaccinated mice. In addition, protection against tumor challenge in vaccinated mice showed that there was no significant change in mice survival after in vivo CD8 þ CTL depletion, indicating that antitumor immunity augmented by plasmid encoding GM-CSF and target PDTRP gene vaccine was dominated by Th2 immune response.

A Phase 1/2 Study of Autologous Neuroblastoma Tumor Cells Genetically Modified to Secrete IL-2 in Patients With High-risk Neuroblastoma

“…With an improved understanding of the contribution of CD4 effector cells to the maintenance of CD8 effectors in vivo 13 and the demonstration that CD4 cells may themselves provide direct antitumor activity, 14,15 the focus has shifted from CD8 responses alone. Indeed, more recent studies have confirmed that clinically measurable tumor responses, 16,17 including those directed to neuroblastoma cells, 18,19 may be obtained irrespective of the polarization of the immune response induced. Although the CD4 and CD8 responses we measured were blocked by CD4 and CD8 directed antibodies, constraints on PBMCs availability from these heavily pretreated pediatric patients precluded additional testing of the effects of MHC class I and class II blocking antibodies.…”

Induction of antigen-specific CTL and antibody responses in mice by a novel recombinant tandem repeat DNA vaccine targeting at mucin 1 of pancreatic cancer

“…Therefore, the new TR DNA vaccine, just encoding one TR polypeptide, is expected to eliminate immunosuppression of unfavorable sequences and to augment the MUC1-specific immune responses. TR polypeptide, a 20 amino-polypeptides of MUC1 which is a tumor-associated antigen of pancreatic cancer, is however with weak antigenicity (Chu et al 2006). To increase the antigenicity of TR polypeptide, a KOZAK sequence and a signal peptide sequence of MCP-1 was inserted continuously before TR sequence in our new pTR plasmid.…”

Peripheral blood CD4+CRTH2+ cells in advanced stage non small cell lung cancer

“…The antitumour effect of Th2 cells has often been shown. Firstly, studies showed that the transfusion of Th2 cells inhibited tumour growth [13][14][15]. Secondly, interleukin-4 (IL-4), a Th2 cytokine, has been found to cause tumour inhibition [6].…”