Tumor cell membrane-based vaccines: A potential boost for cancer immunotherapy

Abstract

Because therapeutic cancer vaccines can, in theory, eliminate tumor cells specifically with relatively low toxicity, they have long been considered for application in repressing cancer progression. Traditional cancer vaccines containing a single or a few discrete tumor epitopes have failed in the clinic, possibly due to challenges in epitope selection, target downregulation, cancer cell heterogeneity, tumor microenvironment immunosuppression, or a lack of vaccine immunogenicity. Whole cancer cell or cancer membrane vaccines, which provide a rich source of antigens, are emerging as viable alternatives. Autologous and allogenic cellular cancer vaccines have been evaluated as clinical treatments. Tumor cell membranes (TCMs) are an intriguing antigen source, as they provide membrane-accessible targets and, at the same time, serve as integrated carriers of vaccine adjuvants and other therapeutic agents. This review provides a summary of the properties and technologies for TCM cancer vaccines. Characteristics, categories, mechanisms, and preparation methods are discussed, as are the demonstrable additional benefits derived from combining TCM vaccines with chemotherapy, sonodynamic therapy, phototherapy, and oncolytic viruses. Further research in chemistry, biomedicine, cancer immunology, and bioinformatics to address current drawbacks could facilitate the clinical adoption of TCM vaccines.

Keywords: cancer immunotherapy; cancer vaccine; tumor cell membrane; tumor‐derived extracellular vesicles.

FIGURE 1

The cascade of tumor elimination via tumor cell membrane (TCM) and tumor‐derived extracellular vesicles. Dendritic cells (DCs) capture tumor information by TCM and its derivation. After antigen processing, DCs present antigen peptide‐loaded major histocompatibility complex (MHC I) complexes on surfaces, activating multiple specific T cells. Cytotoxic T lymphocytes infiltrate in tumor microenvironment and kill tumor cells after recognition of tumor antigens, resulting in the release of tumor debris which is taken by DCs and initiates the next cycle of anti‐tumor immune response.

FIGURE 2

Tumor cell membrane (TCM) wrapped nanoparticle vaccines made by distinct synthetic nanomaterials. The applications and mechanisms of polymeric nanoparticles (NPs), inorganic NPs, and virus particles with TCM were shown.

FIGURE 3

The hybridization of tumor and other cell membrane for tumor vaccines. Tumor and bacterial hybridization is potential to serve as tumor vaccines, for bacterial membrane and outer membrane vesiclesare abundant with pathogen associated molecular patterns (PAMPs) which can trigger innate immunity via the recognition of pattern recognition receptors (PRRs). Antigen‐presenting cells (APCs) express costimulatory molecules that activate CD8+T cells. The combination of tumor and APC membrane functions as artificial APCs while transmit tumor antigens to APCs. Besides, damaged red blood cells highly express phosphatidylserine (PS) which can be recognized by receptors on splenic APCs, and the level of “don't eat me” signal CD47 downregulate, that makes the hybrid membrane of tumor and red blood cells can target and be taken by APCs in spleen.

FIGURE 4

The inflammatory role of tumor‐derived extracellular vesicles (TEVs) in tumor microenvironment. The inherent factors of tumor can guide TEVs into tumor tissue or lymph nodes, which benefit targeting delivery and treatment. Owing to their high fabricability, various of anti‐tumor immunity enhancers can be modified on TEVs and accelerate tumor antigen presentation and reshaping of tumor immunological micro‐environment.

FIGURE 5

The effects of (A) UV‐treated tumor cell MPs (UT‐MPs) and (B) irradiated tumor cell‐released microparticles (RT‐MPs) on APCs.