Engineered Ovalbumin Nanoparticles for Cancer Immunotherapy

Abstract

Ovalbumin (OVA) is a protein antigen that is widely used for eliciting cellular and humoral immune responses in cancer immunotherapy. As an alternative to solute OVA, engineering approach is developed herein towards protein nanoparticles (pNPs) based on reactive electrospraying. The resulting pNPs are comprised of polymerized OVA, where individual OVA molecules are chemically linked via poly(ethylene glycol) (PEG) units. Controlling the PEG/OVA ratio allows for fine-tuning of critical physical properties, such as particle size, elasticity, and, at the molecular level, mesh size. As the PEG/OVA ratio decreased, OVA pNPs are more effectively processed by dendritic cells, resulting in higher OT-I CD8+ cells proliferation in vitro. Moreover, pNPs with lower PEG/OVA ratios elicit enhanced lymphatic drainage in vivo and increased uptake by lymph node macrophages, dendritic cells, and B cells, while 500 nm OVA pNPs show poor draining lymph nodes delivery. In addition, pNPs with lower PEG/OVA ratios result in higher anti-OVA antibody titers in vivo, suggesting improved humoral immune responses. Importantly, OVA pNPs result in significantly increased median survival relative to solute OVA antigen in a mouse model of B16F10-OVA melanoma. This work demonstrates that precisely engineered OVA pNPs can improve the overall anti-tumor response compared to solute antigen. In cancer immunotherapy, eliciting potent and specific immune responses against advanced tumors remains a major challenge. [1] Peptide-based cancer vaccines (subunit vaccines) have been extensively studied in the past, because they have significant advantages (such as safety and ease of manufacturing) over attenuated, inactivated, or biosynthetic vaccines. [2] However,

Targeted Delivery of Drugs and Genes Using Polymer Nanocarriers for Cancer Therapy

“…Keytruda (Pembrolizumab) Checkpoint Inhibitor (PD-1 inhibitor) Melanoma and non-small cell lung cancer [200,201] Yervoy (Ipilimumab) Checkpoint Inhibitor (CTLA-4 inhibitor) Melanoma [202,203] Imfinzi (Durvalumab) Checkpoint Inhibitor (PD-L1 inhibitor) Non-small cell lung cancer [204] Kymriah (Tisagenlecleucel) CAR T-cell therapy Large B-cell lymphoma [205] Provenge (Sipuleucel-T) Cancer Vaccines Prostate cancer [206] Nahal et al developed an approach to protein NP (pNP) engineering based on reactive electrospraying and controlled the particle size, elasticity, and mesh size at the molecular level of the pNP by controlling the PEG/ovalbumin (OVA) ratio [207]. The results showed that the OVA pNPs led to a significant increase in median survival relative to solute OVA antigens in a B16F10-OVA melanoma mouse model.…”

Metal–organic frameworks (MOFs) as host materials for the enhanced delivery of biomacromolecular therapeutics

“…70,71 Ovalbumin (OVA) is a common antigen used for antigen-induced immunotherapy. 72 Zhang et al, developed a pH-responsive Eu-MOF as an antigen delivery system for cancer immunotherapy (Fig. 6).…”

Multifunctional Synthetic Protein Nanoparticles via Reactive Electrojetting

“…[46,47] Novel nanoparticle-based cancer vaccines, where each compartment is made of a different cancer antigen, could provide significant therapeutic advantages. Additionally, the use of functional proteins could also lead to the delivery of protein antigen, [48] active gene therapy enzymes and nucleic acids. Recent work has shown how a treatment based on SPNPs cured mice in an intracranial murine glioblastoma model and prevented subsequent tumor recurrence from a secondary implant, suggesting immunity to cancer recurrence.…”