Engineering anti-cancer nanovaccine based on antigen cross-presentation.

Vaishnavi U. Warrier,Amina I. Makandar,Ravi Kant,Jayanta K. Pal,Manoj Garg,Gautam Sethi,Rajesh Kumar Gupta,Eiji Yuba

doi:10.1042/bsr20193220

Abstract

Dendritic cells (DCs) present exogenous antigens on major histocompatibility complex (MHC) class I molecules, thereby activating CD8+ T cells, contributing to tumor elimination through a mechanism known as antigen cross-presentation. A variety of factors such as maturation state of DCs, co-stimulatory signals, T-cell microenvironment, antigen internalization routes and adjuvants regulate the process of DC-mediated antigen cross-presentation. Recently, the development of successful cancer immunotherapies may be attributed to the ability of DCs to cross-present tumor antigens. In this review article, we focus on the underlying mechanism of antigen cross-presentation and ways to improve antigen cross-presentation in different DC subsets. We have critically summarized the recent developments in the generation of novel nanovaccines for robust CD8+ T-cell response in cancer. In this context, we have reviewed nanocarriers that have been used for cancer immunotherapeutics based on antigen cross-presentation mechanism. Additionally, we have also expressed our views on the future applications of this mechanism in curing cancer.

Highlights

Cancer caused by relentlessly dividing normal cells is a leading cause of death of several individuals
We focus on current developments in cross-presentation based nanocarriers loaded with antigenic peptides for cancer immunotherapy
The conventional treatments for cancer such as surgery, chemotherapy and radiotherapy have shown significant improvements but they have their shortcomings in terms of cancer relapse and are not efficient at later stages in both solid tumors and leukemias [147,148,149,150]

Summary

Introduction

Cancer caused by relentlessly dividing normal cells is a leading cause of death of several individuals. A few anti-cancer vaccines could translate from bench to bedside due to the immune suppression wielded by the tumor [5]. These vaccines often fail to induce an immune response in an already damaged and tumor burdened immune system. The dendritic cells (DCs) exhibit a remarkable ability to phagocytose and present microbial or tumor antigen to CD8+ T cells or CTLs (cytotoxic T lymphocytes) [6,7]. This ability of DCs to cross-present is limited to particular subsets.

Objectives

Conclusion