Bioinspired and Biomimetic Delivery Platforms for Cancer Vaccines

Abstract

However, despite the recent success of ICB and CAR-T therapies in cancer clinical trials, these approaches still face limitations as only a small fraction of patients derive clinical benefit. [4] ICB therapy cannot prime the immune system to specifically recognize or target tumor cells. This approach only works on related inhibitory signaling pathways, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1), and exerts therapeutic efficacy when antigen-specific cytotoxic T lymphocytes (CTLs) are already present. [5] Successful treatment outcomes will therefore require the identification of predictive biomarkers to ascertain if the host tumor will respond to ICB therapeutics administered. [6] Although CAR-T has seen remarkable success in hematological malignancies, response rates of patients with solid tumors remain low. [7] Clinical applications of CAR-T therapies are limited due to on-target/off-tumor toxicities and the need for predefined tumor antigen (Ag). [8] Notwithstanding, the marked progress of immunotherapy using ICB and CAR-T has seen a surge of reinvigorated interest in cancer vaccine development. [9] Cancer vaccines involve the administration of tumor Ags and/or adjuvants to train the immune system to recognize and attack tumor cells. [10] Although vaccines against infectious diseases have been one of the greatest medical accomplishments of modern medicine, the application of vaccines in cancer treatment has seen far lesser success, and, till date only few cancer vaccines have received approval for clinical use. [11] Given their Cancer vaccines aim at eliciting tumor-specific responses for the immune system to identify and eradicate malignant tumor cells while sparing the normal tissues. Furthermore, cancer vaccines can potentially induce long-term immunological memory for antitumor responses, preventing metastasis and cancer recurrence, thus presenting an attractive treatment option in cancer immunotherapy. However, clinical efficacy of cancer vaccines has remained low due to longstanding challenges, such as poor immunogenicity, immunosuppressive tumor microenvironment, tumor heterogeneity, inappropriate immune tolerance, and systemic toxicity. Recently, bioinspired materials and biomimetic technologies have emerged to play a part in reshaping the field of cancer nanomedicine. By mimicking desirable chemical and biological properties in nature, bioinspired engineering of cancer vaccine delivery platforms can effectively transport therapeutic cargos to tumor sites, amplify antigen and adjuvant bioactivities, and enable spatiotemporal control and on-demand immunoactivation. As such, integration of biomimetic designs into delivery platforms for cancer vaccines can enhance efficacy while retaining good safety profiles, which contributes to expediting the clinical translation of cancer vaccines. Recent advances in bioinspired delivery platforms for cancer vaccines, existing obstacles faced, as well as insights and future directions for the field are discu...

Identification of Novel Tumor Antigens and the Immune Landscapes of Bladder Cancer Patients for mRNA Vaccine Development

“…With recent exploration of the tumor microenvironment, there is an increasing awareness of the impact of individual differences on cancer vaccine response (7,25). Identification of specific vaccinesuitable populations is a key issue in mRNA vaccine development.…”

“…Owing to the worldwide spread of COVID-19, mRNA vaccines have received increasing interest (5,6). Although research on traditional cancer vaccines has been conducted for many years, the application of cancer vaccines is still limited (7). At present, only a few areas of mRNA vaccine research have made progress, such as prostate cancer, non-small cell lung cancer, melanoma and so on (8)(9)(10).…”

Three-dimensional (3D) scaffolds as powerful weapons for tumor immunotherapy

“…First, tumor cells manage to display weak immunogenicity by down-regulating the expression of tumor antigens; releasing soluble antigen molecules to induce tumor antibodies binding tumor antigens; reducing the expression of major histocompatibility complex (MHC)-1 proteins limiting efficient antigen presentation; decreasing the secretion of antigen presentation costimulatory factors, etc. The overriding outcome is a significant drop in the amount of recognition of immune cells [ 36 , 37 ]. Second, tumor cells continue to target the immune cells that still work for recognition to interfere with their immune checkpoints.…”

“…As a product with both clinical transformation significance and commercial transformation value, 3D macroscale scaffolds also need to think about mass production and patient compliance [ 37 , 227 ]. Going forward, the 3D macroscale biomaterial-based immunotherapies with great translational potential will open more avenues of modulating the immune responses against more sophisticated diseases.…”

Delivery strategies in treatments of leukemia

“…The emergence of immunotherapy, such as tumor vaccines or immune checkpoint inhibition, has shed new insight into eliciting the body's own immune response and immunologic memory, realizing long-term supervision of the remaining leukemia cells. 269,270 Suitable delivery systems could amplify the antitumor immune responses, and have been reviewed in several studies. 271,272 For leukemia treatment, a Phase I trial (NCT01976520) studies the safety and efficacy of liposomebased vaccines containing an extract of a person's cancer cells and the immunostimulant interleukin-2, which triggered immune response to treat CLL.…”