Microneedle-assisted vaccination combined with autophagy regulation for antitumor immunotherapy

by Selleckchem | Aug 14 2023

Despite vaccination having the potency to revolutionize disease treatments, some critical issues including lack of safe and effective delivery system, insufficient internalization and ineffective antigen cross-presentation by dendritic cells (DCs) severely hamper its extensive clinical applications. Herein, we developed a whole cell-encapsulated antitumor vaccine microneedle patch (TCV-DMNs) potentiated with transdermal co-delivery of granulocyte-macrophage colony-stimulating factor (GM-CSF) and autophagy promoter (Tat-beclin 1). After transdermal vaccination with TCV-DMNs, GM-CSF released from DMNs serves as a potent adjuvant to recruit and promote the phagocytosis of antigens by DCs. Subsequently, Tat-beclin 1 promoted DCs maturation and MHC-I-mediated cross-presentation via up-regulated autophagy of DCs. We found that vaccination with TCV-DMNs could not only effectively suppress melanoma challenge, but also lead to regression of established malignancies, followed by a relapse-free survival of >40 days. Collectively, whole cell-encapsulated microneedle-assisted transdermal vaccination TCV-DMNs in combination with autophagy regulation could induce a robust antitumor immune response via enhancing transdermal delivery efficiency, promoting antigen internalization and cross-presentation, together with boosting T cell activities.

Comments:

The passage you provided describes a novel approach to vaccination called the whole cell-encapsulated antitumor vaccine microneedle patch (TCV-DMNs). This approach aims to overcome some of the challenges associated with traditional vaccination methods. By incorporating a transdermal co-delivery system of granulocyte-macrophage colony-stimulating factor (GM-CSF) and an autophagy promoter (Tat-beclin 1), the TCV-DMNs patch enhances the effectiveness of the vaccine.

When the TCV-DMNs patch is applied to the skin and transdermal vaccination occurs, GM-CSF is released from the microneedles. GM-CSF acts as an adjuvant, which helps to attract and stimulate the phagocytosis of antigens by dendritic cells (DCs). This recruitment and activation of DCs is crucial for initiating an immune response.

In addition to the adjuvant effect of GM-CSF, the Tat-beclin 1 component of the TCV-DMNs patch promotes the maturation of DCs and enhances MHC-I-mediated cross-presentation. This is achieved by up-regulating autophagy in DCs, which is a cellular process involved in the breakdown and recycling of cellular components. The enhanced autophagy in DCs facilitates the processing and presentation of antigens to T cells, leading to a more robust immune response.

The researchers found that vaccination with TCV-DMNs was effective not only in suppressing melanoma challenges but also in causing regression of established malignancies. Furthermore, the vaccinated subjects experienced a relapse-free survival period of over 40 days.

Overall, the whole cell-encapsulated microneedle-assisted transdermal vaccination using TCV-DMNs, along with autophagy regulation, demonstrated the ability to induce a strong antitumor immune response. This approach improves transdermal delivery efficiency, enhances antigen internalization and cross-presentation, and boosts the activity of T cells. These findings suggest that TCV-DMNs could be a promising strategy for developing effective antitumor vaccines.