Table 2.

Summary of recent advancements in nanovaccines for cancer immunotherapy

Incorporated moiety	Nanocarrier system	Mechanistic insights	Reference
Chicken ovalbumin (OVA241–270)	pH-sensitive proton-driven polymeric peptide nano-transformer based vaccine	In the presence of an acidic endosomal microenvironment, the nanotransformer vaccine alters its morphology from nanospheres (100 nm diameter wide) into sheets (few μm in length) disturbing the endosomal membrane and delivering the antigenic peptide into the cytoplasm thereby boosting immunity. It proficiently inhibited tumor growth in the B16F10-OVA and human papilloma virus-E6/E7 induced tumor models in mice. Merging the nano-transformer attributes with anti-PD-L1 antibodies resulted in survival greater than 83 days with complete tumor regression in half of the mice.	(Gong et al., 2020)
Peptide based neoantigen (adpgk)	PEG-PLA nanoparticles	The immunogenic potential of the neoantigen was substantially enhanced by proficient co-delivery of neoantigen and two adjuvants. Immune checkpoint pathways with PD-1 on T cells were sensitized leading to 70% neoantigen specific tumor regression without recurrence.	(Ni et al., 2020)
Curcumin and CpG-ODN	Thermo-sensitive polymeric nanoparticles	Thermo-sensitive curcumin containing polymer nanoparticles incorporated within the hydrogel matrix promoted immunogenic cell death and subsequently improved tumor immunogenicity in vivo. The cancer nanovaccine consisted of CpG-ODN and cationic polymer which activated DC and provoked strong vaccine-mediated T cell immune reactions. In the presence of malignant breast carcinoma 4T1 models, the combination immunotherapy augmented the host T cell immunity, encouraged the accumulation of CTL within the tumor, and diminished tumor recurrence and pulmonary metastasis.	(Xiang Liu et al., 2020)
Ovalbumin	Mesoporous silica-polyethyleneimine (PEI) nanoparticles coated with a metal phenolic network	The pH and reduction dual-sensitive nanovaccine core contained PEI-amended mesoporous silica nanoparticles encapsulated with ovalbumin and the shell was composed of a disulfide bond-involved metal-phenolic network. Smart release in the presence of glutathione and not in neutral phosphate buffer along with in vitro cellular assays indicated the increase in ovalbumin uptake by DC along with lysosomal escape attributed to the proton sponge effect. In vivo studies revealed that the prepared nanoparticles prompted a substantial tumor-specific immune response.	(X. Zhou et al., 2020)
Ovalbumin	Cationic fluoropolymer nanoparticles	Nanoparticles prepared by an admixture of the cationic fluoropolymer with ovalbumin caused DC maturation via TLR 4-mediated signalling and encouraged antigen translocation within the cytosol of DC leading to effective antigen cross-presentation. Mixture of the fluoropolymer and cell membranes from primary tumors injected alongside checkpoint inhibitors inhibited post-surgical tumor recurrence and metastasis in two skin cancer models and an orthotopic breast cancer model.	(Xu et al., 2020)
CpG oligonucleotide	Lipid nanoparticles	CpG-embedded lipid nanoparticles demonstrated potent antitumor efficiency in prophylactic as well as therapeutic E.G7 tumor models. The vaccine promoted T cell exhaustion by enriching PD-1 expression resulting in tumor recurrence. Combination with anti-PD-1 antibody led to similar therapeutic efficacy compared to the nanovaccine administered individually. Adequate therapeutic efficacy after first cycle of immunization with the nanovaccine resulted in tumor relapse suppression indicating checkpoint blockade therapy.	(Y. Kim et al., 2020)
Ovalbumin	MnO2 and polydopamine nanoparticles	The prepared nanoparticles demonstrated outstanding anticancer activity against orthotopic melanoma and could additionally prevent liver metastasis in a tumor re-challenge mouse model. The relocation of DC in the inguinal lymph node was observed by magnetic resonance imaging implying successful DC initiation and immunity generation.	(B. Xiao et al., 2021)
Ovalbumin and CpG ODN	Graphene oxide and PEI	The graphene oxide-PEI nanocomposite vaccine increased DC induction and maturation, antigen cross presentation and cytokine responses against B16F10 melanoma tumors demonstrating prolonged survival time.	(L. Zhang et al., 2022)
Ovalbumin	Mn2+ ions and meso-2,6-diaminopimelic acid (DAP)	Stimulation of DC by Nod1 pathway with migration into lymph nodes was detected by MRI and fluorescence imaging in vivo. Substantial prophylactic as well as anti-tumor activity against B16F10 tumors was observed.	(H. Zhao et al., 2019)
Ovalbumin and CpG	Polyamidoamine dendrimer modified with guanidine-benzoic acid	The dendrimer based nanovaccines showed outstanding prophylactic activity with excellent therapeutic potential indicated by 40% survival up to 60 days compared to control group which showed complete mortality within 30 days.	(Xu et al., 2019)