Strategies for Cancer Immunotherapy Using Induced Pluripotency Stem Cells-Based Vaccines

Abstract

Despite improvements in cancer therapy, metastatic solid tumors remain largely incurable. Immunotherapy has emerged as a pioneering and promising approach for cancer therapy and management, and in particular intended for advanced tumors unresponsive to current therapeutics. In cancer immunotherapy, components of the immune system are exploited to eliminate cancer cells and treat patients. The recent clinical successes of immune checkpoint blockade and chimeric antigen receptor T cell therapies represent a turning point in cancer treatment. Despite their potential success, current approaches depend on efficient tumor antigen presentation which are often inaccessible, and most tumors turn refractory to current immunotherapy. Patient-derived induced pluripotent stem cells (iPSCs) have been shown to share several characteristics with cancer (stem) cells (CSCs), eliciting a specific anti-tumoral response when injected in rodent cancer models. Indeed, artificial cellular reprogramming has been widely compared to the biogenesis of CSCs. Here, we will discuss the state-of-the-art on the potential implication of cellular reprogramming and iPSCs for the design of patient-specific immunotherapeutic strategies, debating the similarities between iPSCs and cancer cells and introducing potential strategies that could enhance the efficiency and therapeutic potential of iPSCs-based cancer vaccines.

A splenic-targeted versatile antigen courier: iPSC wrapped in coalescent erythrocyte-liposome as tumor nanovaccine

“…In recent years, the preparation technology of induced pluripotent stem cells (iPSCs) is widely used in organ transplantation and other fields ( 12 – 14 ). Kooreman et al ( 15 ) reported that iPSCs and cancer cells have common epitopes and iPSCs share a larger cancer-related epitope library, which indicates that vaccines based on it could provide a large number of tumor antigens for the immune system ( 16 , 17 ), so as to establish wide-spectrum antitumor immunity for durable tumor regression in a broad variety of cancers ( 18 ), but the intact cells as vaccine have serious defects such as the following: (i) The iPSCs that have the ability of differentiation must be treated with mitomycin C or γ-radiation before use to avoid tumorigenicity, so intact iPSCs as vaccine have potential safety hazards ( 15 ). (ii) The size of intact iPSC is 10 to 15 μm, and the relatively large size makes it easy to be intercepted by the lung and other tissues after being injected into the body ( 19 ).…”

Development of cell-based vaccines in cancer treatment

“…Since a large number of tumors associated antigens have been discovered, certain features expressed during embryonic development can also be recovered in adults with cancer. Upwards of 100 human tumor-related and tumor-specific antigens, which are protein signals that the immune response may identify, as well as several cancer-related genes are among the genetic and transcriptome properties shared by human iPSC and tumor tissues [5]. The large number of overlapping gene expression profiles of cancer cells and iPSC confirmed the feasibility of using iPSCbased vaccines to generate extensive tumor immunity against multiple cancer types, indicating that the vaccine can equip the immune response with several specific antigens and activate the immune recognition system in patients [6].…”

“…In addition, iPSC reprogramming and status maintenance still have limitations. In conclusion, although the current iPSC vaccine seems to exceed the risk somewhat, it still needs to explore the long-term impact of iPSC-based tumor vaccine on patients after receiving treatment in a large number of clinical settings [5].…”

The Potential of Induced Pluripotent Stem Cells to Advance the Treatment of Pancreatic Ductal Adenocarcinoma

“…The first clinical use of iPSC-based cancer vaccines is yet to be seen, but the above-mentioned preclinical studies demonstrate the potential of these vaccines to elicit anti-PDAC immune responses. In addition to PDAC therapy, iPSC-based antitumor vaccination could potentially serve as a promising universal approach in a broad spectrum of cancer types, including mesothelioma, breast cancer, and melanoma (reviewed in [ 96 ]) [ 65 , 97 , 98 , 99 ]. Tumorigenic properties of iPSCs necessitate lethal irradiation of the iPSCs prior to injection into patients to avoid a potential risk of tumor formation (reviewed in [ 100 , 101 ]) [ 65 , 68 , 102 , 103 ].…”