Single-Walled Carbon Nanotubes Deliver Peptide Antigen into Dendritic Cells and Enhance IgG Responses to Tumor-Associated Antigens

Abstract

We studied the feasibility of using single-wall carbon nanotubes (SWNTs) as antigen carriers to improve immune responses to peptides that are weak immunogens, a characteristic typical of human tumor antigens. Binding and presentation of peptide antigens by the MHC molecules of antigen presenting cells (APCs) is essential to mounting an effective immune response. The Wilm’s tumor protein (WT1) is upregulated in many human leukemias and cancers and several vaccines directed at this protein are in human clinical trials. WT1 peptide 427 induces human CD4 T cell responses in the context of multiple human HLA-DR.B1 molecules, but the peptide has a poor binding affinity to BALB/c mouse MHC class II molecules. We used novel, spectrally quantifiable chemical approaches to covalently append large numbers of peptide ligands (0.4 mmol/g) onto solubilized SWNT scaffolds. Peptide-SWNT constructs were rapidly internalized into professional APCs (dendritic cells and macrophages) within minutes in vitro, in a dose dependent manner. Immunization of BALB/c mice with the SWNT–peptide constructs mixed with immunological adjuvant induced specific IgG responses against the peptide, while the peptide alone or peptide mixed with the adjuvant did not induce such a response. The conjugation of the peptide to SWNT did not enhance the peptide-specific CD4 T cell response in human and mouse cells, in vitro. The solubilized SWNTs alone were nontoxic in vitro, and we did not detect antibody responses to SWNT in vivo. These results demonstrated that SWNTs are able to serve as antigen carriers for delivery into APCs to induce humoral immune responses against weak tumor antigens.

Carbon nanotube interaction with extracellular matrix proteins producing scaffolds for tissue engineering

“…81 It is also possible to decorate CNTs with other nanoparticles, such as silver or gold, 82 carbohydrate molecules, 49,83,84 or peptides. 85 This property makes CNTs efficient when it comes to being as similar as possible to the ECM. It is through the implantation of desirable molecules on the nanotube surface that can promote the interconnection between the numerous pores of the support, in order to obtain a more integrated network.…”

Carbon nanotube-protein carriers enhance size-dependent self-adjuvant antibody response to haptens

“…Their results showed that this derivative, together with ovalbumin and an adjuvant, elicited high virus-neutralizing antibody responses in comparison with the non-conjugated peptide. Since this work, the advantages of immunization with proteins and 95 peptides using CNTs have occasionally been confirmed, [55][56][57][58] but, to the best of our knowledge, no evidence of an enhancement in the immune response and antibody production against small molecules using CNTs as vehicles has been reported. The production of antibodies displaying highaffinity and specificity to haptens is an important biotechnological research field because tailor-made binders can be used to develop immunoassays and biosensors for targets such as medicinal drugs, 100 pesticides, drugs of abuse, environmental contaminants, food additives, hormones, toxins, etc.…”

The Advances of Carbon Nanotubes in Cancer Diagnostics and Therapeutics

“…In order to enhance the efficacy of TCV, the oxidized MWCNTs can be covalently coupled with tumor lysate proteins by an amide bond. On the other hand, Villa et al have developed the capacity of SWCNTs to act as antigen presenting carries to increase the response to weak immunogenic peptides [117]. The Wilms tumor protein (WT1) was covalently conjugated with SWCNTs, and this modification makes it become a vaccine target for many human cancers.…”