Compositions and methods for the treatment and prevention of cancer

Abstract

The present disclosure relates to compositions comprising a population of immunomodulatory lipid nanoparticles, as well as methods of using thereof to treat and / or prevent cancer (e.g., via local administration to the lymph nodes) and methods of using thereof to treat and / or prevent cancer metastasis in a subject.

Description

[0001]Attorney Docket No.11555-011WO1 COMPOSITIONS AND METHODS FOR THE TREATMENT AND PREVENTION OF CANCER GOVERNMENT SUPPORT CLAUSE This invention was made with government support under Grant No. K22CA262355 awarded by the National Institutes of Health (NIH). The Government has certain rights in the invention. CROSS-REFERENCE TO RELATED APPLICATIONS This application claims benefit of priority of U.S. Provisional Application No. 63 / 658,800, filed June 11, 2024, which is hereby incorporated by reference in its entirety. BACKGROUND Cancer is one of the deadliest illnesses in the United States. It accounts for nearly 600,000 deaths annually, and costs billions of dollars for those who suffer from the disease. This disease is in fact a diverse group of disorders, which can originate in almost any tissue of the body. In addition, cancers may be generated by multiple mechanisms including pathogenic infections, mutations, and environmental insults (see, e.g., Pratt et al., Hum. Pathol.36:861-70, 2005). The variety of cancer types and mechanisms of tumorigenesis add to the difficulty associated with treating a tumor, increasing the risk posed by the cancer to the patient's life and wellbeing. Current cancer treatments include, among others, surgery, chemotherapeutics, radiation therapy, immunotherapy, and photodynamic therapy. However, none of these treatments is completely effective, and each has its own associated side effects. Further, hypoxia is a characteristic feature of locally advanced solid cancers resulting from an imbalance between oxygen supply and consumption (see Vaupel et al., Oncologist 9 Suppl. 5:4-9, 2004). Cancer tumor hypoxia can reduce the effectiveness of radiotherapy, some oxygen-dependent cytotoxic agents, and photodynamic therapy. Invasive tumor growth and metastasis require angiogenesis, a physiological process involving the growth of new blood vessels and improved delivery of oxygen to oxygen- starving tumors. It is considered advantageous to prevent oxygen and nutrient delivery to tumors, and numerous studies have evaluated the use of angiogenesis inhibitors to suppress tumor growth (see, e.g., Folkman, Semin. Oncol.29:15-18, 2002). Such inhibitors Attorney Docket No.11555-011WO1 cut off the supply of oxygen to tumors, starving the tumors of oxygen and leading to apoptosis. The first angiogenesis inhibitors for cancer have now been approved by the FDA in the U.S. and in 28 other countries. The majority of these are monotherapies that block VEGF (see, e.g., Folkman, Exp. Cell. Res.312:594-607, 2006). However, these drugs can have side effects, such as increasing the risk of internal bleeding, increasing the risk of developing a hole in the digestive tract, and raising blood pressure. Further, cancer tumor hypoxia can induce changes in the proteome and genome of neoplastic cells that further survival and malignant progression by enabling the cells to overcome nutritive deprivation or to escape their hostile environment. Cancer vaccines have been a subject of much attention. Various kinds of cancer vaccines, including tumor vaccines have been developed (Pardoll, D. M., Nature Med., 4(5 Suppl), pp.525-531, 1998). Roughly tumor vaccines can be categorized depending on tumor-specific materials as follows: (1) vaccines wherein a tumor antigenic peptide with a known property is used; (2) vaccines wherein a tumor tissue extract containing an unidentified tumor antigenic peptide is used; (3) vaccines wherein the above peptide is bound to an antigen-presenting cell, especially a dendritic cell with a strong capability of antigen presentation (Nestle et al., Nature Med., 4, pp.328-332, 1998); (4) vaccines wherein a tumor antigenic protein is taken into a dendritic cell and loaded; (5) vaccines wherein a dendritic cell and a tumor cell are fused; (6) vaccines wherein a tumor antigen is bound to a liposome for uptake together with the liposome (Nakanishi et al., Biochem. Biophys. Res. Comm., 240, pp.793-797, 1997); (7) vaccines wherein a tumor cell, per se, is treated for inactivation with radiation or a fixing agent before administration; (8) vaccines wherein a cytokine gene, having an antigen-presenting cell stimulating effect or a lymphocyte stimulating effect, is introduced into a tumor cell and the cell is administered as a vaccine for a gene therapy, or wherein a tumor antigenic gene is introduced into a suitable cell and a tumor cell expressing the gene is administered as a vaccine; (9) vaccines wherein a tumor antigenic gene is integrated into a virus or a bacterium for infection of a patient; (10) vaccines wherein a live tumor cell, a tumor antigenic peptide or an extract of a tumor cell is administered, and separately a great amount of a cytokine is administered (Rosenberg et al., Nature Med., 4, pp.321-327, 1998), or wherein a cytokine is formulated into a controlled release preparation and administered (Golumbek, P. T., et al., Cancer Res., 53, pp.5841-5844, 1993) and the like. While many strategies have been evaluated, there remains a significant need for new and effective compositions and methods of treating and preventing cancer. Attorney Docket No.11555-011WO1 SUMMARY Provided herein are methods of treating and / or preventing cancer in a subject. These methods can comprise administering to the subject a composition comprising a population of immunomodulatory lipid nanoparticles. The immunomodulatory lipid nanoparticles comprise (a) a lipid-based nanoparticle carrier and (b) a (STING) pathway agonist and a (TLR4) agonist co-encapsulated within the lipid-based nanoparticle carrier. In some embodiments, the population of immunomodulatory nanoparticles have an average particle size, as determined by dynamic light scattering (DLS), of from 25 nm to 250 nm, such as an average particle size of from 25 nm to 200 nm, an average particle size of from 25 nm to 150 nm, an average particle size of from 25 nm to 150 nm, or an average particle size of from 30 nm to 80 nm. In some embodiments, the composition is administered locally to the subject. For example, the composition can be administered by subcutaneous injection, intradermal injection, or intramuscular injection. Upon administration, the population of immunomodulatory lipid nanoparticles can preferentially accumulate in a lymph node in the subject. In some embodiments, the composition further comprises one or more tumor antigens. The tumor antigen can comprise any suitable tumor antigen, such as one or more tumor antigenic peptides, a nucleic acid encoding for a tumor antigen, or any combination thereof. In some embodiments, the composition further comprises a tumor lysate or an extract thereof. In some cases, the tumor lysate can be obtained from a biopsy or tissue sample collected from the subject. The lipid-based nanoparticle carrier can comprise any suitable nanoparticle carrier comprising one or more lipids. In some embodiments, the lipid-based nanoparticle carrier is selected from the group consisting of a liposome, a lipid nanoparticle (also referred to herein as a solid lipid nanoparticle), and a nanostructured lipid carrier (NLC). In certain embodiments, the lipid-based nanoparticle carrier is a lipid nanoparticle. In some embodiments, the lipid nanoparticle comprises one or more neutral lipids and one or more PEGylated lipids. In certain embodiments, the lipid nanoparticle comprises 85 mol% to 99.5 mol% one or more neutral lipids; and 0.5 mol% to 15 mol% one or more PEGylated lipids. In some examples, the one more neutral lipids are selected from the group consisting of dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylethanolamine (DOPE), 1,2-Dioleoyl-sn-glycero-3-phosphocholine Attorney Docket No.11555-011WO1 (DOPC), palmitoyloleoylphosphatidylcholine (POPC), egg phosphatidylcholine (EPC), distearoylphosphatidylcholine (DSPC), cholesterol, or any combination thereof. In some examples, the one more neutral lipids are selected from the group consisting of a PEG- ditetradecylacetamide, a PEG-myristoyl diglyceride, a PEG-diacylglycerol, a PEG dialkyloxypropyl, a PEG-phospholipid, a PEG-ceramide, PEG-DMG, PEG-DSPE, or any combination thereof. In some examples, the TLR4 agonist comprises a lipopolysaccharide (LPS) derivative or analog thereof. In certain examples, the TLR4 agonist comprises a lipid A analog, variant, derivative, or mimetic. In certain examples, the TLR4 agonist comprises monophosphoryl lipid A (MPLA). In some examples, the STING pathway agonist comprising a cyclic dinucleotide (CDN). In certain examples, the CDN selected from the group consisting of cyclic dimeric guanosine monophosphate (cdGMP), cyclic dimeric adenosine monophosphate (cdAMP), and cyclic GMP-AMP (cGAMP). In certain examples, the CDN comprising cyclic diguanylate monophosphate (cdGMP). In some embodiments, the STING pathway agonist and the TLR4 agonist are present in the lipid-based nanoparticle carrier at a molar ratio of STING pathway agonist:TLR4 agonist of from 0.5:1 to 5:1 (e.g., from 1:1 to 3:1, or from 1:1 to 2.5:1). In some embodiments, the immunomodulatory lipid nanoparticles further comprise one or more targeting moieties. The one or more targeting moieties can be covalently linked to the immunomodulatory lipid nanoparticles. In certain embodiments, the one or more targeting moieties are covalently linked to PEGylated lipids present in the immunomodulatory lipid nanoparticles. The one or more targeting moieties can comprise any suitable moieties (e.g., peptides, nucleic acids such as aptamers, etc.) that bind to or otherwise target or recognize targets overexpressed in tumor cells and / or present in the tumor microenvironment. In some examples, the one or more targeting moieties are selected from the group consisting of a peptide that binds to fibrin-fibronectin extracellular matrix, a peptide that binds to P-selectin, a peptide that binds to ^^^3 integrins, a peptide that binds to epidermal growth factor receptor (EGFR), or a combination thereof. Also provided herein are methods of treating and / or preventing cancer metastasis in a subject. These methods can comprise administering to the subject a composition comprising a population of immunomodulatory lipid nanoparticles. The immunomodulatory lipid nanoparticles can comprise (a) a lipid-based nanoparticle carrier; (b) a (STING) pathway agonist and a (TLR4) agonist co-encapsulated within the lipid-based Attorney Docket No.11555-011WO1 nanoparticle carrier; and (c) one or more targeting moieties are covalently linked to the immunomodulatory lipid nanoparticles. In some embodiments, the cancer metastasis comprises a dormant metastasis. In some embodiments, the cancer metastasis comprises an aggressive metastasis. In some embodiments, the one or more targeting moieties are covalently linked to PEGylated lipids present in the immunomodulatory lipid nanoparticles. The one or more targeting moieties can comprise any suitable moieties (e.g., peptides, nucleic acids such as aptamers, etc.) that bind to or otherwise target or recognize targets overexpressed in tumor cells and / or present in the tumor microenvironment. In some examples, the one or more targeting moieties are selected from the group consisting of a peptide that binds to fibrin- fibronectin extracellular matrix, a peptide that binds to P-selectin, a peptide that binds to ^^^3 integrins, a peptide that binds to epidermal growth factor receptor (EGFR), or a combination thereof. In some embodiments, the composition is administered systemically to the subject. In certain embodiments, the composition is administered by intravenous injection. In some embodiments, the population of immunomodulatory nanoparticles have an average particle size, as determined by dynamic light scattering (DLS), of from 25 nm to 250 nm, such as an average particle size of from 25 nm to 200 nm, an average particle size of from 25 nm to 150 nm, an average particle size of from 25 nm to 150 nm, or an average particle size of from 30 nm to 80 nm. The lipid-based nanoparticle carrier can comprise any suitable nanoparticle carrier comprising one or more lipids. In some embodiments, the lipid-based nanoparticle carrier is selected from the group consisting of a liposome, a lipid nanoparticle (also referred to herein as a solid lipid nanoparticle), and a nanostructured lipid carrier (NLC). In certain embodiments, the lipid-based nanoparticle carrier is a lipid nanoparticle. In some embodiments, the lipid nanoparticle comprises one or more neutral lipids and one or more PEGylated lipids. In certain embodiments, the lipid nanoparticle comprises 85 mol% to 99.5 mol% one or more neutral lipids; and 0.5 mol% to 15 mol% one or more PEGylated lipids. In some examples, the one more neutral lipids are selected from the group consisting of dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylethanolamine (DOPE), 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC), palmitoyloleoylphosphatidylcholine (POPC), egg phosphatidylcholine (EPC), distearoylphosphatidylcholine (DSPC), cholesterol, or any combination thereof. In some examples, the one more neutral lipids are selected from the group consisting of a PEG- Attorney Docket No.11555-011WO1 ditetradecylacetamide, a PEG-myristoyl diglyceride, a PEG-diacylglycerol, a PEG dialkyloxypropyl, a PEG-phospholipid, a PEG-ceramide, PEG-DMG, PEG-DSPE, or any combination thereof. In some examples, the TLR4 agonist comprises a lipopolysaccharide (LPS) derivative or analog thereof. In certain examples, the TLR4 agonist comprises a lipid A analog, variant, derivative, or mimetic. In certain examples, the TLR4 agonist comprises monophosphoryl lipid A (MPLA). In some examples, the STING pathway agonist comprising a cyclic dinucleotide (CDN). In certain examples, the CDN selected from the group consisting of cyclic dimeric guanosine monophosphate (cdGMP), cyclic dimeric adenosine monophosphate (cdAMP), and cyclic GMP-AMP (cGAMP). In certain examples, the CDN comprising cyclic diguanylate monophosphate (cdGMP). In some embodiments, the STING pathway agonist and the TLR4 agonist are present in the lipid-based nanoparticle carrier at a molar ratio of STING pathway agonist:TLR4 agonist of from 0.5:1 to 5:1 (e.g., from 1:1 to 3:1, or from 1:1 to 2.5:1). The details of one or more embodiments of the disclosure are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the disclosure will be apparent from the description and drawings, and from the claims. DESCRIPTION OF DRAWINGS Figures 1A-1D illustrate the structure and size of dual-agonist loaded immuno-NPs conjugated to one or more tumor antigenic peptides. These immunomodulatory lipid nanoparticles can function as a “super-adjuvant” to drive enhanced CD8+ T cell priming via lymph-node directed delivery in the tissue. Figures 2A-2C illustrate preliminary experiments demonstrating the ability of immuno-NP-peptide formulations the drive antigen-specific CD8+ T cell responses when administered systemically. Figures 3A-3F show the ability of multivalent immune-NPs to elicit enhanced circulating tumor-specific CD8+ T cell populations as compared to single peptide formulations. Figures 4A-4E show the ability of “super-adjuvant” immuno-NPs to drain to lymph nodes from subcutaneous tissue following local administration (e.g., via subcutaneous injection). Attorney Docket No.11555-011WO1 Figures 5A-5C illustrate the ability of multivalent “super-adjuvant” immune-NP- peptides to confer immunity to a subsequent B16F10 challenge. Figures 6A-6G illustrate tailoring NP engineering to augment cytokine synergy and antigen presentation. (Figure 6A) Schematic of “super adjuvant” NP coencapsulating cdGMP and MPLA. Prepared with BioRender.com. (Figure 6B) Schematic representation of shared downstream signaling effectors of STING and TLR4 pathways that drives synergistic production of proinflammatory cytokines upon dual activation. Prepared with BioRender.com. (Figure 6C) Multiplex cytokine analysis of supernatant from culture of 1 x 106RAW264.7 macrophages after treatment with NPs for 24 hr containing varying doses of cdGMP (3, 23, 45 µM) and / or MPLA (1, 10, 20 µM) at 10 mg / mL total NP concentration (N = 3 biological replicates per group). For all conditions, the overall concentration of lipid nanoparticles was 10 mg / mL. (Figure 6D) IFN^ and IFN^ ELISA from supernatant of culture of 1 x 106primary splenic CD11c+DCs treated for 24 hr with the indicated NP formulation (N = 3 biological replicates per group). (Figure 6E) IFN^ and IFN^ ELISA from supernatant of culture of 1 x 106cells of the indicated iBMDMs treated for 24 hr with the indicated NP formulation (N = 3 biological replicates per group). (Figure 6F) IFN^ ELISA from supernatant of culture of 1 x 106human DCs treated for 24 h with the indicated formulation (N = 4 biological replicates per group per patient) (Figure 6G) RT-qPCR analysis of gene expression related to antigen presentation and processing in 2 x 106primary CD11c+DCs treated with the indicated NP formulation for 24 hr (N = 3 biological replicates per group). A.U., arbitrary units. Error bars, ± SEM. P values were calculated using 2-way ANOVA. **** P < 0.0001, *** P < 0.001, ** P < 0.01, * P < 0.05, n.s, not significant. Figures 7A-7C illustrate NP draining efficiency to lymph nodes and activation of DCs. (Figure 7A) Quantification of lymph node accumulation via ex vivo Spectrum imaging of inguinal lymph nodes 24 hr post-injection of NPs labeled with lipophilic dye DiI with representative images from each group (N = 3 mice per group). (Figure 7B) Confocal microscopy of immunofluorescence staining of lymph node tissue for NPs, CD11c, CD80, and IFN^ 24 hr post-boost. (Figure 7C) Quantification of mean fluorescent intensity (MFI) from confocal imaging in (Figure 7B) (N = 4 images per group). Error bars, ± SEM. P values were calculated using 2-way ANOVA. **** P < 0.0001, *** P < 0.001, ** P < 0.01, * P < 0.05, n.s, not significant. Attorney Docket No.11555-011WO1 Figures 8A-8E illustrate multivalent peptide vaccination with NPs for prevention of tumor formation and long-term survival. (Figure 8A) Schematic of “super adjuvant” NPs and peptide vaccination regimen using the B16F10 melanoma mouse model. Prepared with BioRender.com. (Figure 8B) Interleaved plots of flow cytometry quantification of the frequency of production of IFN^ and TNF^ by CD8+T cells after ex vivo stimulation of PBMCs at the indicated time point with antigenic peptides for 2 hr prior to staining (N = 5 mice per group). (Figure 8C) Average tumor volume 3 weeks following orthotopic challenge with 0.5 x 106B16F10 cells (N = 10 mice for NPs and peptides, N = 5 mice for other groups). (Figure 8D) Kaplan-Meier survival curve using approximately 1000 mm3tumor volume as the end point (N = 10 mice for NPs and peptides, N = 5 mice for other groups). (Figure 8E) Bar chart indicating percent tumor rejection within the indicated group to local (0.5 x 106cells) and subsequent systemic (1 x 106cells) challenge / rechallenge. Only mice that rejected local challenge were subjected to systemic rechallenge. Additional naive mice were enrolled in the study for systemic rechallenge (for local: N = 10 NPs and peptides, N = 5 all other groups; for systemic: N = 8 NPs and peptides, N = 5 naive). Indicated significance for IFN^+TNF^+populations on interleaved plots in (Figure 8B). Error bars, ± SEM. P values were calculated using 2-way ANOVA. **** P < 0.0001, *** P < 0.001, ** P < 0.01, * P < 0.05, n.s, not significant. Figures 9A-9G illustrate NPs administered with tumor lysate for broad immune responses as a platform approach across multiple models . (Figure 9A) Schematic of “super adjuvant” NPs and lysate vaccination regimen. Prepared with BioRender.com. (Figure 9B) Interleaved plots of flow cytometry quantification of the frequency of production of IFN^ and TNF^ by CD8+and CD4+T cells after ex vivo stimulation of PBMCs at the indicated time point with cell lysate for 2 hr prior to staining (N = 5 mice per group). (Figure 9C) Interleaved plot of flow cytometry quantification of the frequency of production of IFN^ and TNF^ by CD19+B cells after ex vivo stimulation of PBMCs at the indicated time point with cell lysate for 2 hr prior to staining and IgG ELISA from culture supernatant of ex vivo stimulation of PBMCs with lysate for 2 h (N = 5 per group). (Figure 9D) Quantification of polyfunctional CD8+T cells after ex vivo stimulation of circulating PBMCs with lysate for 2 hr at the indicated weeks in mice which did or did not undergo IFNAR depletion bi-weekly throughout the study (N = 5 mice per group). (Figure 9E) Quantification of polyfunctional CD4+T cells after ex vivo stimulation of PBMCs with lysate for 2 hr at the indicated weeks in mice which did or did not undergo IFNAR depletion bi-weekly throughout the study (N = 5 mice per group). (Figure 9F) Kaplan-Meier survival curve using approximately 1000mm3 Attorney Docket No.11555-011WO1 tumor volume as the end point (N = 13 B16F10 NP, N = 8 Panc02 NP and 4T1 NP, N = 5 all other groups). (Figure 9G) Bar chart indicating percent tumor rejection within the indicated group to local (0.5 x 106cells) and subsequent systemic (1 x 106cells) challenge. Only mice that rejected local challenge were subjected to systemic rechallenge. Additional naive mice were enrolled in the study for systemic rechallenge (for local: N = 13 B16F10 NP, N = 8 Panc02 NP and 4T1 NP, N = 5 all other groups; for systemic: N = 7 B16F10 NP and Panc02 NP, N = 64T1 NP, N = 5 all naive). Indicated significance for IFN^+TNFa+on interleaved plots in (B). Error bars, ± SEM. P values were calculated using 2-way ANOVA. **** P < 0.0001, *** P < 0.001, ** P < 0.01, * P < 0.05, n.s, not significant. Figures 10A-10F illustrate tailored engineering for augmentation of cytokine synergy and antigen presentation. (Figure 10A) Dynamic light scattering (DLS) measurements were performed in PBS. (Figure 10B) Zeta-potential measurements of NPs in PBS. (Figure 10C) cdGMP encapsulation was measured after 1 hr dialysis using a Lucerna aptamer-based detection assay and plotted as a percentage of the initial amount of cdGMP added to the synthesis. For timecourse stability, concentration of cdGMP before dialysis was used as baseline. (Figure 10D) cdGMP encapsulation was measured afer 1h dialysis using LC-MS for the indicated formulation. For timecourse stability, concentration of cdGMP before dialysis was used as a baseline. (Figure 10E) Representative LC-MS plots from analysis of the indicated formulation. (Figure 10F) MPLA encapsulation was measured after 1 hr dialysis and plotted as a percentage of the initial amount of MPLA added to the synthesis. For timecourse stability, concentration of MPLA before dialysis was used as baseline. Figures 11A-11G show the results of analysis of the supernatant of cultures. (Figure 11A) IFN^ and IFN^ ELISA from supernatant culture of 1 x 106RAW 264.7 macrophages after treatment for 24 hr with free adjuvants at the indicated concentration. For all conditions, the overall concentration of lipid nanoparticles was 10 mg / mL. (Figure 11B) Multiplex cytokine analysis of supernatant from culture with 1 x 106RAW 264.7 macrophages after 24 hr treatment with NPs containing adjuvant at the indicated concentration. (Figure 11C) Multiplex cytokine analysis of supernatant from culture with 1 x 106CD11c+DCs after 24 hr treatment with the indicated NP formulation. (Figure 11D) Multiplex cytokine analysis of supernatant from culture with 1 x 106WT iBMDMs after 24 hr treatment with the indicated NP formulation. (Figure 11E- Figure 11G) Multiplex cytokine analysis of supernatant from culture with 1 x 106of the indicated iBMDM KO cell line after 24 hr treatment with the indicated NP formulation. All experiments were Attorney Docket No.11555-011WO1 performed in biological triplicates. Error bars, ± SEM. P values were calculated using 2- way ANOVA. **** P < 0.0001, *** P < 0.001, ** P < 0.01, * P < 0.05, n.s, not significant. Figures 12A-12I illustrate the draining of “super adjuvant” NPs to lymph nodes and immune activation. (Figure 12A) Flow cytometry quantification of NP uptake in APCs at the injection site 30 min post-injection of either dual-adjuvant or empty NPs (N = 6 samples group). (Figure 12B) In vivo fluorescent quantification of the percentage of initial dose that drained away from the injection site (tail base) at 1 hr post-injection for the indicated formulations after either a first (prime) or third (second boost) injection of NPs labeled with a lipophilic dye (1 week between each injections) with representative images (for prime: N = 6 dual-adjuvant NP, N = 4 empty NP, for boost: N = 3 dual-adjuvant NP, N = 2 empty NP). (Figure 12C) Representative confocal images of immunofluorescence staining of inguinal lymph node tissue for NPs (red), TNF^ (purple), CD8^ (green), IFN^ (blue) at 24 hr post-boost. (Figure 12D) Quantification of mean fluorescent intensity (MFI) from confocal imaging in (Figure 12C) (N = 4 images per group). (Figure 12E) Quantification of NP accumulation in the indicated organ at 48 h post injection. (Figure 12F) Quantification of NP accumulation in lymph nodes with representative images shown. (Figure 12G) Flow cytometry quantification of circulating CD8+T cells at the indicated timepoint following dose escalation and production of IFN^ and TNF^ by circulating CD8+T cells after ex vivo stimulation with antigenic peptides for 2 hr prior to staining at the indicated time point (N = 3 mice per group). (Figure 12H) ALT / AST levels in blood plasma at 1 week following treatment with the indicated formulation (N=3 mice per group) (Figure 12I) Mouse weights following treatment with either no NPs, half, full, or twice the dose of dual-adjuvant NPs (N = 3 mice per group). Error bars, ± SEM. P values were calculated using 2-way ANOVA. **** P < 0.0001, *** P < 0.001, ** P < 0.01, * P < 0.05, n.s, not significant. Figures 13A-13M illustrate vaccination with single tumor antigenic peptides for CD8+T cell responses. (Figure 13A) DLS measurements of the indicated NP formulations in PBS. (Figure 13B) Zeta-potential measurements of the parent NP formulations for NPs and single peptides in PBS. (Figure 13C) Flow cytometry quantification of circulating CD8+T cells at the indicated time point (N = 5 mice per group). (Figure 13D) Flow cytometry quantification of the frequency of production of IFN^ and TNF^ by circulating CD8+T cells after ex vivo stimulation with antigenic peptides for 2 hr prior to staining at the indicated time point (N = 5 mice per group). (Figure 13E) Interleaved plots showing flow cytometry quantification of cytokine production by CD8+T cells at 1 week post-second boost (N = 5 mice per group). (Figure 13F). Kaplan-Meier survival curve using approximately 1000 Attorney Docket No.11555-011WO1 mm3tumor volume as the end point (N = 5 mice per group). (Figure 13G) Blood plasma from the indicated treatment group was analyzed for ALT at 1 week post-boost (N = 5 mice per group), dotted lines indicate established range for ALT levels. (Figure 13H) Blood plasma from the indicated treatment group was analyzed for AST at 1 week post-boost (N = 5 mice per group), dotted lines indicate established range for AST levels. (Figure 13I) Mouse weights were monitored throughout treatment for all groups (N = 5 mice per group). (Figure 13J) Bar chart indicating percent tumor rejection within the indicated group to local (0.5 x 106cells) and subsequent systemic (1 x 106cells) challenge. (Figure 13K) Flow cytometry quantification of circulating CD8+T cells at the indicated time point for the B16F10-OVA model (N = 5 mice per group). (Figure 13L) Flow cytometry quantification of SIINFEKL tetramer stain with representative gating (N = 5 mice per group). (Figure 13M) Individual tumor volume growth curves for B16F10-OVA model study (N=5 mice per group) (4 / 5 Dual NP + SIINFEKL mice were tumor free at D21). Only mice that rejected local challenges were subjected to systemic challenges. Additional naive mice were enrolled in the study for systemic challenge (for local: N = 5 all groups, for systemic: N = 5 naive, N = 1 all other groups). Indicated significance for IFN^+TNF^+on interleaved plots in (E). Error bars, ± SEM. P values were calculated using 2-way ANOVA. **** P < 0.0001, *** P < 0.001, ** P < 0.01, * P < 0.05, n.s, not significant. Figures 14A-14G illustrate multivalent peptide vaccination for prevention of tumor formation and long-term survival. (Figure 14A) Interleaved plots showing flow cytometry quantification of cytokine production by CD8+T cells after stimulation with Trp1 peptide at the indicated time point (N = 10 peptides and NP, N = 5 all other groups). (Figure 14B) Interleaved plots showing flow cytometry quantification of cytokine production by CD8+T cells after stimulation with Trp2 peptide at the indicated time point (N = 10 peptides and NPs, N = 5 all other groups). (Figure 14C) Interleaved plots showing flow cytometry quantification of cytokine production by CD8+T cells after stimulation with equimolar Trp1 and Trp2 peptides at the indicated time point (N = 10 peptides and NPs, N = 5 all other groups). (Figure 14D) Mouse weights were monitored throughout treatment for all groups (N = 10 peptides and NPs, N = 5 all other groups). (Figure 14E) Individual tumor volume plots for the indicated treatment groups (N = 10 peptides and NPs, N = 5 all other groups). (Figure 14F) Flow cytometry gating strategy for PBMCs at 1 week post-second boost with representative selections of final gating for IFN^+TNF^+cells. (Figure 14G) Representative images of lung metastases at 21 days post-systemic rechallenge. Error bars, ± SEM. Indicated significance for IFN^+TNF^+on interleaved plots in (B). P values were calculated Attorney Docket No.11555-011WO1 using 2-way ANOVA. **** P < 0.0001, *** P < 0.001, ** P < 0.01, * P < 0.05, n.s, not significant. Figures 15A-15J illustrate “super adjuvant” NPs delivered alongside tumor lysate drive for broad immune responses. (Figure 15A) Flow cytometry quantification of the frequency of production of IFN^ and TNF^ by circulating CD8+T cells after ex vivo stimulation with cell lysate for 2 hr prior to staining at the indicated time point (N = 5 mice per group). (Figure 15B) Flow cytometry quantification of the frequency of production of IFN^ and TNF^ by circulating CD4+T cells after ex vivo stimulation with cell lysate for 2 hr prior to staining at the indicated time point (N = 5 mice per group). (Figure 15C) Flow cytometry quantification of the frequency of production of IFN^ and TNF^ by circulating CD19+B cells after ex vivo stimulation with cell lysate for 2 hr prior to staining at the indicated time point (N = 5 mice per group). (Figure 15D) IgG ELISA from culture supernatant of ex vivo stimulation of PBMCs from the indicated time point with lysate for 2 hr (N = 5 mice per group). (Figure 15E) Mouse weights were monitored throughout treatment for all groups (N = 13 for B16F10 NP, N = 8 for Panc02 NP and 4T1 NP, N = 5 mice for all other groups). (Figure 15F- Figure 15H) Individual tumor volume plots for the indicated treatment groups. (Figure 15I) Representative images of lung metastases at 21 days post-systemic rechallenge. (Figure 15J) Representative flow cytometry dot plots for cytokine production from the indicated cell types in the indicated treatment groups at 1 week post-second boost. Error bars, ± SEM. P values were calculated using 2-way ANOVA. **** P < 0.0001, *** P < 0.001, ** P < 0.01, * P < 0.05, n.s, not significant Figures 16A-16E show the rationale used for targeting the nanoparticle formulations described herein. Figure 17 illustrates the characterization of evaluated nanoparticle treatments. Figures 18A-18C show the evaluation of the impact of a single dose of individual targeted nanoparticle formulations. Figures 19A-19B show the evaluation of the impact of increased dosage of targeted nanoparticle formulations. Like reference symbols in the various drawings indicate like elements. DETAILED DESCRIPTION Many modifications and other embodiments disclosed herein will come to mind to one skilled in the art to which the disclosed compositions and methods pertain having the benefit of the teachings presented in the foregoing descriptions and the associated drawings. Attorney Docket No.11555-011WO1 Therefore, it is to be understood that the disclosures are not to be limited to the specific embodiments disclosed and that modifications and other embodiments are intended to be included within the scope of the appended claims. The skilled artisan will recognize many variants and adaptations of the aspects described herein. These variants and adaptations are intended to be included in the teachings of this disclosure and to be encompassed by the claims herein. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation. As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present disclosure. Any recited method can be carried out in the order of events recited or in any other order that is logically possible. That is, unless otherwise expressly stated, it is in no way intended that any method or aspect set forth herein be construed as requiring that its steps be performed in a specific order. Accordingly, where a method claim does not specifically state in the claims or descriptions that the steps are to be limited to a specific order, it is no way intended that an order be inferred, in any respect. This holds for any possible non- express basis for interpretation, including matters of logic with respect to arrangement of steps or operational flow, plain meaning derived from grammatical organization or punctuation, or the number or type of aspects described in the specification. All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and / or materials in connection with which the publications are cited. The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided herein can be different from the actual publication dates, which can require independent confirmation. While aspects of the present disclosure can be described and claimed in a particular statutory class, such as the system statutory class, this is for convenience only and one of skill in the art will understand that each aspect of the present disclosure can be described and claimed in any statutory class. It is also to be understood that the terminology used herein is for the purpose of Attorney Docket No.11555-011WO1 describing particular aspects only and is not intended to be limiting. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosed compositions and methods belong. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the specification and relevant art and should not be interpreted in an idealized or overly formal sense unless expressly defined herein. Prior to describing the various aspects of the present disclosure, the following definitions are provided and should be used unless otherwise indicated. Additional terms may be defined elsewhere in the present disclosure. Definitions As used herein, “comprising” is to be interpreted as specifying the presence of the stated features, integers, steps, or components as referred to, but does not preclude the presence or addition of one or more features, integers, steps, or components, or groups thereof. Moreover, each of the terms “by”, “comprising,” “comprises”, “comprised of,” “including,” “includes,” “included,” “involving,” “involves,” “involved,” and “such as” are used in their open, non-limiting sense and may be used interchangeably. Further, the term “comprising” is intended to include examples and aspects encompassed by the terms “consisting essentially of” and “consisting of.” Similarly, the term “consisting essentially of” is intended to include examples encompassed by the term “consisting of. As used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “an ocular therapeutic composition,” “a therapeutic agent,” or “a clinical condition,” includes, but is not limited to, two or more such ocular therapeutic compositions, therapeutic agents, or clinical conditions, and the like. It should be noted that ratios, concentrations, amounts, and other numerical data can be expressed herein in a range format. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as “about” that particular value in addition to the value itself. For example, if the value “10” is disclosed, then “about 10” is also disclosed. Ranges can be expressed herein as from “about” one particular value, and / or to “about” another particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular Attorney Docket No.11555-011WO1 value forms a further aspect. For example, if the value “about 10” is disclosed, then “10” is also disclosed. When a range is expressed, a further aspect includes from the one particular value and / or to the other particular value. For example, where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure, e.g. the phrase “x to y” includes the range from ‘x’ to ‘y’ as well as the range greater than ‘x’ and less than ‘y’. The range can also be expressed as an upper limit, e.g. ‘about x, y, z, or less’ and should be interpreted to include the specific ranges of ‘about x’, ‘about y’, and ‘about z’ as well as the ranges of ‘less than x’, less than y’, and ‘less than z’. Likewise, the phrase ‘about x, y, z, or greater’ should be interpreted to include the specific ranges of ‘about x’, ‘about y’, and ‘about z’ as well as the ranges of ‘greater than x’, greater than y’, and ‘greater than z’. In addition, the phrase “about ‘x’ to ‘y’”, where ‘x’ and ‘y’ are numerical values, includes “about ‘x’ to about ‘y’”. It is to be understood that such a range format is used for convenience and brevity, and thus, should be interpreted in a flexible manner to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub- range is explicitly recited. To illustrate, a numerical range of “about 0.1% to 5%” should be interpreted to include not only the explicitly recited values of about 0.1% to about 5%, but also include individual values (e.g., about 1%, about 2%, about 3%, and about 4%) and the sub-ranges (e.g., about 0.5% to about 1.1%; about 5% to about 2.4%; about 0.5% to about 3.2%, and about 0.5% to about 4.4%, and other possible sub-ranges) within the indicated range. As used herein, the terms “about,” “approximate,” “at or about,” and “substantially” mean that the amount or value in question can be the exact value or a value that provides equivalent results or effects as recited in the claims or taught herein. That is, it is understood that amounts, sizes, formulations, parameters, and other quantities and characteristics are not and need not be exact, but may be approximate and / or larger or smaller, as desired, reflecting tolerances, conversion factors, rounding off, measurement error and the like, and other factors known to those of skill in the art such that equivalent results or effects are obtained. In some circumstances, the value that provides equivalent results or effects cannot be reasonably determined. In such cases, it is generally understood, as used herein, that “about” and “at or about” mean the nominal value indicated ±10% variation unless otherwise indicated or inferred. In general, an amount, size, formulation, parameter or other Attorney Docket No.11555-011WO1 quantity or characteristic is “about,” “approximate,” or “at or about” whether or not expressly stated to be such. It is understood that where “about,” “approximate,” or “at or about” is used before a quantitative value, the parameter also includes the specific quantitative value itself, unless specifically stated otherwise. As used herein, “effective amount” can refer to the amount of a disclosed compound or pharmaceutical composition provided herein that is sufficient to effect beneficial or desired biological, emotional, medical, or clinical response of a cell, tissue, system, animal, or human. An effective amount can be administered in one or more administrations, applications, or dosages. The term can also include within its scope amounts effective to enhance or restore to substantially normal physiological function. As used herein, the term “therapeutically effective amount” refers to an amount that is sufficient to achieve the desired therapeutic result or to have an effect on undesired symptoms but is generally insufficient to cause adverse side effects. The specific therapeutically effective dose level for any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration; the route of administration; the rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed and like factors within the knowledge and expertise of the health practitioner and which may be well known in the medical arts. In the case of treating a particular disease or condition, in some instances, the desired response can be inhibiting the progression of the disease or condition. This may involve only slowing the progression of the disease temporarily. However, in other instances, it may be desirable to halt the progression of the disease permanently. This can be monitored by routine diagnostic methods known to one of ordinary skill in the art for any particular disease. The desired response to treatment of the disease or condition also can be delaying the onset or even preventing the onset of the disease or condition. For example, it is well within the skill of the art to start doses of a compound at levels lower than those required to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved. If desired, the effective daily dose can be divided into multiple doses for purposes of administration. Consequently, single dose compositions can contain such amounts or submultiples thereof to make up the daily dose. The dosage can be adjusted by the individual physician in the event of any contraindications. It is generally preferred that a maximum dose of the pharmacological Attorney Docket No.11555-011WO1 agents of the invention (alone or in combination with other therapeutic agents) be used, that is, the highest safe dose according to sound medical judgment. It will be understood by those of ordinary skill in the art however, that a patient may insist upon a lower dose or tolerable dose for medical reasons, psychological reasons or for virtually any other reasons. A response to a therapeutically effective dose of a disclosed drug delivery composition can be measured by determining the physiological effects of the treatment or medication, such as the decrease or lack of disease symptoms following administration of the treatment or pharmacological agent. Other assays will be known to one of ordinary skill in the art and can be employed for measuring the level of the response. The amount of a treatment may be varied for example by increasing or decreasing the amount of a disclosed compound and / or pharmaceutical composition, by changing the disclosed compound and / or pharmaceutical composition administered, by changing the route of administration, by changing the dosage timing and so on. Dosage can vary, and can be administered in one or more dose administrations daily, for one or several days. Guidance can be found in the literature for appropriate dosages for given classes of pharmaceutical products. As used herein, the term “prophylactically effective amount” refers to an amount effective for preventing onset or initiation of a disease or condition. As used herein, the terms "treating" and "treatment" can refer generally to obtaining a desired pharmacological and / or physiological effect. The effect can be, but does not necessarily have to be, prophylactic in terms of preventing or partially preventing a disease, symptom or condition thereof, such as an ophthalmological disorder. The effect can be therapeutic in terms of a partial or complete cure of a disease, condition, symptom or adverse effect attributed to the disease, disorder, or condition. The term "treatment" as used herein can include any treatment of cancer in a subject, particularly a human and can include any one or more of the following: (a) preventing the disease from occurring in a subject which may be predisposed to the disease but has not yet been diagnosed as having it; (b) inhibiting the disease, i.e., arresting its development; and (c) relieving the disease, i.e., mitigating or ameliorating the disease and / or its symptoms or conditions. The term "treatment" as used herein can refer to both therapeutic treatment alone, prophylactic treatment alone, or both therapeutic and prophylactic treatment. Those in need of treatment (subjects in need thereof) can include those already with the disorder and / or those in which the disorder is to be prevented. As used herein, the term "treating", can include inhibiting the disease, disorder or condition, e.g., impeding its progress; and relieving the disease, disorder, or condition, e.g., causing regression of the disease, disorder and / or condition. Attorney Docket No.11555-011WO1 Treating the disease, disorder, or condition can include ameliorating at least one symptom of the particular disease, disorder, or condition, even if the underlying pathophysiology is not affected, e.g., such as treating the pain of a subject by administration of an analgesic agent even though such agent does not treat the cause of the pain. As used herein, the terms “treating” or “treatment” of a disease can refer to executing a treatment protocol to eradicate at least one diseased cell. Thus, “treating” or “treatment” does not require complete eradication of diseased cells. As used herein, the term “prevent” or “preventing” refers to precluding, averting, obviating, forestalling, stopping, or hindering something from happening, especially by advance action. It is understood that where reduce, inhibit or prevent are used herein, unless specifically indicated otherwise, the use of the other two words is also expressly disclosed. As used herein, the terms “optional” or “optionally” means that the subsequently described event or circumstance can or cannot occur, and that the description includes instances where said event or circumstance occurs and instances where it does not. As used herein, the term “sample” can refer to a specimen or culture obtained from any source, as well as clinical, research, biological and environmental samples. Biological samples may be obtained from animals (including humans) and encompass cells, fluids, solids, tissues, and organs, and whole organisms. As used herein, the term “subject” can refer to any animal including, but not limited to, humans and non-human animals (e.g., rodents, arthropods, insects, fish (e.g., zebrafish)), non-human primates, ovines, bovines, ruminants, lagomorphs, porcines, caprines, equines, or canines felines, aves, etc.). "Subject" can also refer to a cell, a population of cells, a tissue, an organ, or an organism, preferably to human and constituents thereof. As used herein, the terms “cancer” or “tumor” refer to any neoplastic growth in a subject, including an initial tumor and any metastases. The cancer can be of the liquid or solid tumor type. Liquid tumors include tumors of hematological origin, including, e.g., myelomas (e.g., multiple myeloma), leukemias (e.g., Waldenstrom's syndrome, chronic lymphocytic leukemia, other leukemias), and lymphomas (e.g., B-cell lymphomas, non- Hodgkin's lymphoma). Solid tumors can originate in organs and include cancers of the lungs, brain, breasts, prostate, ovaries, colon, kidneys and liver. As used herein, the terms “cancer cell” or “tumor cell” can refer to cells that divide at an abnormal (i.e., increased) rate. Cancer cells include, but are not limited to, carcinomas, such as squamous cell carcinoma, non-small cell carcinoma (e.g., non-small cell lung carcinoma), small cell carcinoma (e.g., small cell lung carcinoma), basal cell carcinoma, Attorney Docket No.11555-011WO1 sweat gland carcinoma, sebaceous gland carcinoma, adenocarcinoma, papillary carcinoma, papillary adenocarcinoma, cystadenocarcinoma, medullary carcinoma, undifferentiated carcinoma, bronchogenic carcinoma, melanoma, renal cell carcinoma, hepatoma-liver cell carcinoma, bile duct carcinoma, cholangiocarcinoma, papillary carcinoma, transitional cell carcinoma, choriocarcinoma, semonoma, embryonal carcinoma, mammary carcinomas, gastrointestinal carcinoma, colonic carcinomas, bladder carcinoma, prostate carcinoma, and squamous cell carcinoma of the neck and head region; sarcomas, such as fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordosarcoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, synoviosarcoma and mesotheliosarcoma; hematologic cancers, such as myelomas, leukemias (e.g., acute myelogenous leukemia, chronic lymphocytic leukemia, granulocytic leukemia, monocytic leukemia, lymphocytic leukemia), lymphomas (e.g., follicular lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, malignant lymphoma, plasmocytoma, reticulum cell sarcoma, or Hodgkin's disease), and tumors of the nervous system including glioma, glioblastoma multiform, meningoma, medulloblastoma, schwannoma and epidymoma. As used herein, the term “polynucleotide” can refer to oligonucleotides, nucleotides, or to a fragment of any of these, to DNA or RNA (e.g., mRNA, rRNA, tRNA) of genomic or synthetic origin, which may be single-stranded or double-stranded and may represent a sense or antisense strand, to peptide nucleic acids, or to any DNA-like or RNA-like material, natural or synthetic in origin, including, e.g., iRNA, ribonucleoproteins (e.g., iRNPs). The term can also encompass nucleic acids, i.e., oligonucleotides, containing known analogues of natural nucleotides. The term can also encompass nucleic acid-like structures with synthetic backbones. As used herein, the term “polypeptide” can refer to an oligopeptide, peptide, polypeptide, or protein sequence, or to a fragment, portion, or subunit of any of these, and to naturally occurring or synthetic molecules. The term “polypeptide” can also include amino acids joined to each other by peptide bonds or modified peptide bonds, i.e., peptide isosteres, and may contain any type of modified amino acids. The term can also include peptides and polypeptide fragments, motifs and the like, glycosylated polypeptides, and all “mimetic” and “peptidomimetic” polypeptide forms. As used herein, the term “small molecule” can refer to lipids, carbohydrates, polynucleotides, polypeptides, or any other organic or inorganic molecules. In some embodiments, the term “small molecule” can refer to a molecule having a molecular weight of 1,000 Daltons or less (e.g., 900 Daltons or less, 800 Daltons or less, 750 Daltons or less, Attorney Docket No.11555-011WO1 700 Daltons or less, 600 Daltons or less, or 500 Daltons or less) As used herein, the term “targeting moiety” can refer to a molecule or molecules that are able to bind to and complex with a biomarker. The term can also refer to a functional group that serves to target or direct a nanoparticle, therapeutic agent or anti- cancer agent to a particular location, cell type, diseased tissue, or association. In general, a “targeting moiety” can be directed against a biomarker. As used herein, the term “molecular signature” can refer to a unique expression pattern of one or more biomarkers (e.g., gene(s) or protein(s)) of a cell. As used herein, the term “antibody” refers to an immunoglobulin, derivatives thereof which maintain specific binding ability, and proteins having a binding domain which is homologous or largely homologous to an immunoglobulin binding domain. These proteins may be derived from natural sources, or partly or wholly synthetically produced. An antibody may be monoclonal or polyclonal. The antibody may be a member of any immunoglobulin class, including any of the human classes: IgG, IgM, IgA, IgD, and IgE. In exemplary embodiments, antibodies used with the methods and compositions described herein are derivatives of the IgG class. As used herein, the term “antibody fragment” refers to any derivative of an antibody which is less than full-length. In exemplary embodiments, the antibody fragment retains at least a significant portion of the full-length antibody's specific binding ability. Examples of antibody fragments include, but are not limited to, Fab, Fab^, F(ab^)2, scFv, Fv, dsFv diabody, and Fd fragments. The antibody fragment may be produced by any means. For instance, the antibody fragment may be enzymatically or chemically produced by fragmentation of an intact antibody, it may be recombinantly produced from a gene encoding the partial antibody sequence, or it may be wholly or partially synthetically produced. The antibody fragment may optionally be a single chain antibody fragment. Alternatively, the fragment may comprise multiple chains which are linked together, for instance, by disulfide linkages. The fragment may also optionally be a multimolecular complex. A functional antibody fragment will typically comprise at least about 10 amino acids and more typically will comprise at least about 200 amino acids. As used herein, the term “diabodies” refers to dimeric scFvs. The components of diabodies typically have shorter peptide linkers than most scFvs and they show a preference for associating as dimers. As used herein, the term “epitope” refers to a physical structure on a molecule that interacts with a selective component. In exemplary embodiments, epitope refers to a desired Attorney Docket No.11555-011WO1 region on a target molecule that specifically interacts with a selectivity component. As used herein, the term “Fab^” refers to an antibody fragment that is essentially equivalent to that obtained by reduction of the disulfide bridge or bridges joining the two heavy chain pieces in the F(ab^)2fragment. Such fragments may be enzymatically or chemically produced by fragmentation of an intact antibody, recombinantly produced from a gene encoding the partial antibody sequence, or it may be wholly or partially synthetically produced. As used herein, the term “F(ab^)2” refers to an antibody fragment that is essentially equivalent to a fragment obtained by digestion of an immunoglobulin (typically IgG) with the enzyme pepsin at pH 4.0-4.5. Such fragments may be enzymatically or chemically produced by fragmentation of an intact antibody, recombinantly produced from a gene encoding the partial antibody sequence, or it may be wholly or partially synthetically produced. As used herein, the term “Fv” refers to an antibody fragment that consists of one VH and one VL domain held together by noncovalent interactions. The term “dsFv” is used herein to refer to an Fv with an engineered intermolecular disulfide bond to stabilize the VH- VL pair. As used herein, the term “immunogen” traditionally refers to compounds that are used to elicit an immune response in an animal and is used as such herein. However, many techniques used to produce a desired selectivity component, such as the phage display and aptamer methods described below, do not rely wholly, or even in part, on animal immunizations. Nevertheless, these methods use compounds containing an “epitope,” as defined above, to select for and clonally expand a population of selectivity components specific to the “epitope.” These in vitro methods mimic the selection and clonal expansion of immune cells in vivo, and, therefore, the compounds containing the “epitope” that is used to clonally expand a desired population of phage, aptamers and the like in vitro are embraced within the definition of “immunogens”. As used herein, the terms “single-chain Fvs” and “scFvs” refers to recombinant antibody fragments consisting of only the variable light chain (VL) and variable heavy chain (VH) covalently connected to one another by a polypeptide linker. Either VLor VHmay be the NH2-terminal domain. The polypeptide linker may be of variable length and composition so long as the two variable domains are bridged without serious steric interference. In exemplary embodiments, the linkers are comprised primarily of stretches of glycine and serine residues with some glutamic acid or lysine residues interspersed for Attorney Docket No.11555-011WO1 solubility. As used herein, “therapeutic agent” can refer to any substance, compound, molecule, and the like, which can be biologically active or otherwise can induce a pharmacologic, immunogenic, biologic and / or physiologic effect on a subject to which it is administered to by local and / or systemic action. A therapeutic agent can be a primary active agent, or in other words, the component(s) of a composition to which the whole or part of the effect of the composition is attributed. A therapeutic agent can be a secondary therapeutic agent, or in other words, the component(s) of a composition to which an additional part and / or other effect of the composition is attributed. The term therefore encompasses those compounds or chemicals traditionally regarded as drugs, vaccines, and biopharmaceuticals including molecules such as proteins, peptides, hormones, nucleic acids, gene constructs and the like. Examples of therapeutic agents are described in well-known literature references such as the Merck Index (14th edition), the Physicians' Desk Reference (64th edition), and The Pharmacological Basis of Therapeutics (12th edition), and they include, without limitation, medicaments; vitamins; mineral supplements; substances used for the treatment, prevention, diagnosis, cure or mitigation of a disease or illness; substances that affect the structure or function of the body, or pro-drugs, which become biologically active or more active after they have been placed in a physiological environment. For example, the term “therapeutic agent” includes compounds or compositions for use in all of the major therapeutic areas including, but not limited to, adjuvants; anti-infectives such as antibiotics and antiviral agents; analgesics and analgesic combinations, anorexics, anti-inflammatory agents, anti- epileptics, local and general anesthetics, hypnotics, sedatives, antipsychotic agents, neuroleptic agents, antidepressants, anxiolytics, antagonists, neuron blocking agents, anticholinergic and cholinomimetic agents, antimuscarinic and muscarinic agents, antiadrenergics, antiarrhythmics, antihypertensive agents, hormones, and nutrients, antiarthritics, antiasthmatic agents, anticonvulsants, antihistamines, antinauseants, antineoplastics, antipruritics, antipyretics; antispasmodics, cardiovascular preparations (including calcium channel blockers, beta-blockers, beta-agonists and antiarrythmics), antihypertensives, diuretics, vasodilators; central nervous system stimulants; cough and cold preparations; decongestants; diagnostics; hormones; bone growth stimulants and bone resorption inhibitors; immunosuppressives; muscle relaxants; psychostimulants; sedatives; tranquilizers; proteins, peptides, and fragments thereof (whether naturally occurring, chemically synthesized or recombinantly produced); and nucleic acid molecules (polymeric forms of two or more nucleotides, either ribonucleotides (RNA) or deoxyribonucleotides Attorney Docket No.11555-011WO1 (DNA) including both double- and single-stranded molecules, gene constructs, expression vectors, antisense molecules and the like), small molecules (e.g., doxorubicin) and other biologically active macromolecules such as, for example, proteins and enzymes. The agent may be a biologically active agent used in medical, including veterinary, applications and in agriculture, such as with plants, as well as other areas. The term therapeutic agent also includes without limitation, medicaments; vitamins; mineral supplements; substances used for the treatment, prevention, diagnosis, cure or mitigation of disease or illness; or substances which affect the structure or function of the body; or pro- drugs, which become biologically active or more active after they have been placed in a predetermined physiological environment. It is understood that disclosure herein of a therapeutic agent also disclosed pharmaceutically acceptable salt, pharmaceutically acceptable ester, pharmaceutically acceptable amide, prodrug forms, and derivates of the therapeutic agent. The term “pharmaceutically acceptable salts”, as used herein, means salts of the active principal agents which are prepared with acids or bases that are tolerated by a biological system or tolerated by a subject or tolerated by a biological system and tolerated by a subject when administered in a therapeutically effective amount. When compounds of the present disclosure contain relatively acidic functionalities, base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired base, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable base addition salts include, but are not limited to: sodium, potassium, calcium, ammonium, organic amino, magnesium salt, lithium salt, strontium salt or a similar salt. When compounds of the present disclosure contain relatively basic functionalities, acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired acid, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include, but are not limited to; those derived from inorganic acids like hydrochloric, hydrobromic, nitric, carbonic, monohydrogencarbonic, phosphoric, monohydrogenphosphoric, dihydrogenphosphoric, sulfuric, monohydrogensulfuric, hydriodic, or phosphorous acids and the like, as well as the salts derived from relatively nontoxic organic acids like acetic, propionic, isobutyric, maleic, malonic, benzoic, succinic, suberic, fumaric, lactic, mandelic, phthalic, benzenesulfonic, p-tolylsulfonic, citric, tartaric, methanesulfonic, and the like. Also included are salts of amino acids such as arginate and the like, and salts of organic acids like glucuronic or galactunoric acids and the like. Attorney Docket No.11555-011WO1 The term “pharmaceutically acceptable ester” refers to esters of compounds of the present disclosure which hydrolyze in vivo and include those that break down readily in the human body to leave the parent compound or a salt thereof. Examples of pharmaceutically acceptable, non-toxic esters of the present disclosure include C 1 -to-C 6 alkyl esters and C 5 -to-C 7 cycloalkyl esters, although C 1 -to-C 4 alkyl esters are preferred. Esters of disclosed compounds can be prepared according to conventional methods. Pharmaceutically acceptable esters can be appended onto hydroxy groups by reaction of the compound that contains the hydroxy group with acid and an alkylcarboxylic acid such as acetic acid, or with acid and an arylcarboxylic acid such as benzoic acid. In the case of compounds containing carboxylic acid groups, the pharmaceutically acceptable esters are prepared from compounds containing the carboxylic acid groups by reaction of the compound with base such as triethylamine and an alkyl halide, for example with methyl iodide, benzyl iodide, cyclopentyl iodide or alkyl triflate. They also can be prepared by reaction of the compound with an acid such as hydrochloric acid and an alcohol such as ethanol or methanol. The term “pharmaceutically acceptable amide” refers to non-toxic amides of the present disclosure derived from ammonia, primary C 1 -to-C 6 alkyl amines and secondary C 1 -to-C 6 dialkyl amines. In the case of secondary amines, the amine can also be in the form of a 5- or 6-membered heterocycle containing one nitrogen atom. Amides derived from ammonia, C 1 -to-C 3 alkyl primary amides and C 1 -to-C 2 dialkyl secondary amides are preferred. Amides of disclosed compounds can be prepared according to conventional methods. Pharmaceutically acceptable amides can be prepared from compounds containing primary or secondary amine groups by reaction of the compound that contains the amino group with an alkyl anhydride, aryl anhydride, acyl halide, or aroyl halide. In the case of compounds containing carboxylic acid groups, the pharmaceutically acceptable amides are prepared from compounds containing the carboxylic acid groups by reaction of the compound with base such as triethylamine, a dehydrating agent such as dicyclohexyl carbodiimide or carbonyl diimidazole, and an alkyl amine, dialkylamine, for example with methylamine, diethylamine, and piperidine. They also can be prepared by reaction of the compound with an acid such as sulfuric acid and an alkylcarboxylic acid such as acetic acid, or with acid and an arylcarboxylic acid such as benzoic acid under dehydrating conditions such as with molecular sieves added. The composition can contain a compound of the present disclosure in the form of a pharmaceutically acceptable prodrug. The term “pharmaceutically acceptable prodrug” or “prodrug” represents those prodrugs of the compounds of the present disclosure which are, within the scope of sound Attorney Docket No.11555-011WO1 medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit / risk ratio, and effective for their intended use. Prodrugs of the present disclosure can be rapidly transformed in vivo to a parent compound having a structure of a disclosed compound, for example, by hydrolysis in blood. A thorough discussion is provided in T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, V.14 of the A.C.S. Symposium Series, and in Edward B. Roche, ed., Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press (1987). As used herein, “kit” means a collection of at least two components constituting the kit. Together, the components constitute a functional unit for a given purpose. Individual member components may be physically packaged together or separately. For example, a kit comprising an instruction for using the kit may or may not physically include the instruction with other individual member components. Instead, the instruction can be supplied as a separate member component, either in a paper form or an electronic form which may be supplied on computer readable memory device or downloaded from an internet website, or as recorded presentation. As used herein, “instruction(s)” means documents describing relevant materials or methodologies pertaining to a kit. These materials may include any combination of the following: background information, list of components and their availability information (purchase information, etc.), brief or detailed protocols for using the kit, trouble-shooting, references, technical support, and any other related documents. Instructions can be supplied with the kit or as a separate member component, either as a paper form or an electronic form which may be supplied on computer readable memory device or downloaded from an internet website, or as recorded presentation. Instructions can comprise one or multiple documents and are meant to include future updates. As used herein, “dose,” “unit dose,” or “dosage” can refer to physically discrete units suitable for use in a subject, each unit containing a predetermined quantity of a disclosed compound and / or a pharmaceutical composition thereof calculated to produce the desired response or responses in association with its administration. As used herein, the term “tumor antigen” comprises all substances, which elicit an immune response against a tumor. Examples of tumor antigens include cancer-associated antigens belonging to gene products of mutated or recombined cellular genes, tumor virus antigens, overexpressed or tissue-specific differentiation antigens, and widely expressed antigens; or fragments or derivatives of any of the foregoing. Specific examples of a tumor Attorney Docket No.11555-011WO1 antigen include cyclin-dependent kinase 4 (CDK4), p15Ink4b, p53, AFP, ^-catenin, caspase 8, p53, p21Rasmutations, Bcr-abl fusion product, MUM-1 MUM-2, MUM-3, ELF2M, HSP70-2M, HST-2, KIAA0205, RAGE, myosin / m, 707-AP, CDC27 / m, ETV6 / AML, TEL / Aml1, Dekcain, LDLR / FUT, Pml-RAR^TEL / AMLI, NY-ESO-1, members of the MAGE-family (MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-10, MAGE-12), BAGE, DAM-6, DAM-10, members of the GAGE-family (GAGE-1, GAGE-2, GAGE-3, GAGE-4, GAGE-5, GAGE-6, GAGE-7B, GAGE-8), NA-88A, CAG-3, RCC- associated antigen G250, human papilloma virus (HPV)-derived E6 E7 oncoproteins, Epstein Barr virus EBNA2-6, LMP-1, LMP-2, gp77, gp100, MART-1 / Melan-A, p53, tyrosinase, tyrosinase-related protein (TRP-1 and TPR-2), PSA, PSM, MC1R, ART4, CAMEL, CEA, CypB, HER2 / neu, hTERT, hTRT, iCE, Muc1, Muc2, PRAME RU1, RU2, SART-1, SART-2, SART-3, and WT1. Compositions and Methods of Use This application is generally related to immunomodulatory nanoparticles for co- delivery of loaded anti-tumor agents to cancer cells and / or tumor sites and to their use in therapeutic applications. Co-encapsulating anti-tumor agents within nanoparticle carriers to form an immuno-nanoparticle construct can allow for their co-delivery to the same target cell. Interferon ^ (IFN^) drives robust innate immunity, natural killer (NK) cell activity, and APC (dendritic cell and macrophage)-mediated activation of CD8+ T cells and is also pivotal in preventing malignant transformation and de-differentiating cancer stem cells. It was shown that upon target cell internalization of an immunomodulatory nanoparticles, the released synergistic immune-potentiating agents co-loaded in a nanoparticle carrier can trigger a robust site-specific cytokine gradient driven largely by IFN^ that results in APC- and NK cell-driven local and systemic immune recruitment. In some examples, the immunomodulatory nanoparticles had an average particle size (diameter) of ~60-nm with a PEG shell. In some examples, these immunomodulatory nanoparticles were injected locally in the tissue via subcutaneous injection to home to lymph nodes. These immunomodulatory nanoparticles were co-administered these NPs with antigenic peptides against B16F10 melanoma and were shown to: (1) drain rapidly to lymph nodes following subcutaneous administration, (2) be taken up by dendritic cells that prime vaccine-specific responses by CD8+ T cells, and (3) promote both prophylactic and therapeutic vaccination responses in mice with immunological memory to protect against Attorney Docket No.11555-011WO1 tumor recurrence In some examples, the immunomodulatory nanoparticles were targeted to alpha5- beta3 integrins, P-selectin, EGFR, or fibrin-fibronectin extracellular matrix. Integrins and EGFR are highly expressed on tumor cells across multiple cancer types. Integrins and P- selectin are expressed on tumor-associated vasculature. Unique fibrin-fibronectin motifs are found on the tumor extracellular matrix across cancer types. These immunomodulatory nanoparticles were tested in two isogenic models of metastasis, the D2.HAN models of lung cancer, including the D2.OR (dormant) and D2.A1 (aggressive) models, and the 4T models of triple-negative breast cancer, including the 4T07 (dormant) and 4T1 (aggressive) models. These studies suggested that dormant metastasis may be more readily treatable as tumor cells are quiescent compared to aggressive tumor cells that are highly proliferative. Effective treatment of dormant metastasis following targeted NP therapy can lead to immunological protection of isogenic aggressive cancers, highlighting that the compositions described herein (targeted to features present in the TME) can confer protection against recurrence of multiple related tumor types without requiring prior knowledge of specific tumor antigens. Further, these studies suggest that even key non-immune cell types within the TME can be exploited for immunotherapy, including cells that highly express STING and TLR sensing machinery, such as fibroblasts and endothelial cells. Finally, either by targeting them directly and / or targeting other cells in the TME, these studies suggest that tumor cells can also be exploited as a pivotal source of antigens for immune recognition and subsequent clearance. This finding was unexpected as tumor cells are known to downregulate their innate sensing pathways. Specifically, dormant tumor cells may be coaxed out of their quiescent state by promoting their Type I IFN production, effectively unmasking them, and enabling their immune recognition. Immunomodulatory Lipid Nanoparticles The compositions described herein can comprise a population of immunomodulatory lipid nanoparticles. The immunomodulatory lipid nanoparticles can comprise (a) a lipid-based nanoparticle carrier and (b) a (STING) pathway agonist and a (TLR4) agonist co-encapsulated within the lipid-based nanoparticle carrier. The nanoparticle carrier of the immunomodulatory lipid nanoparticles described herein may be uniform (e.g., being about the same size) or of variable size. Nanoparticle carriers for use in a construct described herein are ideally nanoparticle carriers capable of protecting cargo from degradation, avoiding non-specific distribution throughout the body that can lead to systemic toxicity and delivering to disease site and facilitate direct uptake Attorney Docket No.11555-011WO1 by specific cell subpopulations. In some embodiments, the nanoparticle carrier can have a size that facilitates extravasation of the immuno-nanoparticle construct in cancer therapy allowing the constructs to be taken up by the peripheral APCs or drained from interstitial spaces to the lymphatic lumen and then transported to draining lymph nodes. Typically, the nanoparticle carrier, even when loaded with therapeutic agents, can have an average particle size, as determined by dynamic light scattering (DLS), of from 25 nm to 250 nm, such as an average particle size of from 25 nm to 200 nm, an average particle size of from 25 nm to 150 nm, an average particle size of from 25 nm to 150 nm, or an average particle size of from 30 nm to 80 nm. Nanoparticle carriers with diameter of approximately 50-70 nm have been found to be especially efficient at uptake and retention in lymph nodes. In an exemplary embodiment, the nanoparticle carrier, can have an average diameter of about 60 nm. In some embodiments, the nanoparticle carrier of an immunomodulatory lipid nanoparticles can include a lipid-based nanoparticle or polymeric nanoparticle. Lipid-based nanoparticles are a broad and diverse group of nanoparticles that have a high degree of biocompatibility and can encapsulate a wide range of cargos. Lipid-based nanoparticles for use in an immuno-nanoparticle construct described herein can include, but are not limited to, liposomes, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC). Polymeric nanoparticles can include, but are not limited to, poly(beta-amino ester) (PBAE), and pH-responsive polymersomes. Additional nanoparticles for use as a nanocarrier in a construct described herein can include cationic silica nanoparticles (CSiNPs) and lipid coated silica microspheres. In some embodiments, the nanoparticle carrier is a liposome nanoparticle. The main component of liposomes are phospoholipids, which are organized into a bilayer structure due to their amphipathic properties. In the presence of water, they form vesicles improving the solubility and stability of anti-tumor agents once they are loaded into their structure. Liposomes can have positive charges and aqueous cores. The positive charge on liposomes can promote the encapsulation of negatively charged agents and can also facilitate intracellular liposome delivery by electrostatically interactive with negatively charged cell membranes. Liposome nanocarriers can include, but are not limited to, PEG-containing or PEGylated lipids, pH-sensitive cationic lipids, or a soy-PC-DOTAP liposome. In addition to phospholipids, other compounds can be added to liposome formulations, such as cholesterol, to decrease the fluidity of the nanoparticle and increase the permeability of hydrophobic drugs through the bilayer membrane, improving the stability of these Attorney Docket No.11555-011WO1 nanoparticles in blood. In on example, an immuno-nanoparticle construct can include about 60 nm liposomes prepared from equimolar quantities of DOPC and DPPC and 3 mol % mPEG2000-DSPE. In some embodiments, the nanoparticle carrier is a SLN or NLC lipid-based nanoparticle carrier. SLNs are a colloidal drug delivery system composed of physiological lipids that remain in a solid state at both room and body temperature. The solid lipid used forms a matrix material for drug encapsulation and can include mono-, di- or triglycerides, fatty acids and complex glyceride mixtures. The matrix is typically stabilized by a mixture of surfactants or polymers. NLCs, which were developed from SLNs, can include a mixture of solid and liquid lipids, such as glyceryl tricaprylate, ethyl oleate, isopropyl myristate and glyceryl dioleate. In other embodiments, the nanoparticle carrier of the immuno-nanoparticle construct can include a mesoporous silica nanocore (MSN). The mesoporous silica protects anti- tumor agents loaded within the nanocore and provides support for surface modification of the MSNs with functional groups. MSNs can be prepared using a base-catalyzed sol-gel process enhanced by the surfactant cetyltrimethylammonium bromide (CTAB) to produce highly ordered mesoporous silica layer. Additionally, various functional groups can be introduced onto the silica surface using well known methods in order to conjugate the nanoparticles with other molecules or substrates. Use of the term “mesoporous silica” does not preclude materials other than mesoporous silica from also being incorporated within or on the surface of the silica nanocore. In some embodiments, the mesoporous silica nanocore may be substantially spherical with a plurality of pore openings through the surface providing access to the pores. However, the mesoporous silica nanocore can have shapes other than substantially spherical shapes in other embodiments of the current invention. Generally, a layer of mesoporous silica defines an outer surface between the pore openings, as well as side walls within the pores. The pores can extend through a layer of mesoporous silica to another pore opening or can extend only partially through the layer of mesoporous silica such that it has a bottom surface of the pore defined by the layer of mesoporous silica. The pores of the MSN surface can allow small molecules to diffuse into the outer silica layer of the MSNs. This process, in turn, advantageously allows for highly stable loading of therapeutic anti-tumor immune-potentiating agents with negligible leakage as well as the efficient release of the therapeutic agents from the MSNs from the particle into the cytosol. Attorney Docket No.11555-011WO1 The MSN can be coated around the core with a lipid bilayer. In some embodiments, the lipid bilayer can incorporate lipophilic anti-tumor agents and / or be linked to a targeting moiety. In certain embodiments, the surface of a nanocarrier can be further functionalized to enhance intracellular delivery of the co-loaded agents. For example, the surface of a mesoporous silica nanocore can be functionalized with N1-(3- Trimethoxysilylpropyl)diethylenetriamine to enhance the ability of the nanoparticle construct to escape endosomes, avoid lysosomal degradation and transition to the cytosol to allow for delivery of each agent to its specific intracellular target (e.g., nucleus or ER). Nanoparticle carriers described herein can be chemically modified to avoid detection by the immune system, and / or to improve the solubility of the therapeutic agents loaded therein. For example, nanoparticle carriers can include a poly(ethylene glycol) (PEG) coating for improved solubility and circulation. Therapeutic agents co-loaded into and / or incorporated within a nanoparticle carrier to produce an immuno-nanoparticle construct can include two or more anti-tumor immune- potentiating agents capable of inducing Type I interferons in a subject. For example, therapeutic agents for use in a construct described herein may trigger an immune response by targeting target host pattern recognition receptors (PRRs) expressed by cells of the innate immune system, such as dendritic cells, macrophages, monocytes, neutrophils and epithelial cells. In certain embodiments, the therapeutic agents of an immuno-nanoparticle construct are selected from a stimulator of interferon (IFN) genes (STING) agonist and a Toll-like receptor-4 (TLR4) agonist. In some embodiments, each agent is loaded into a nanocarrier and / or each agent is incorporated within an external layer of the nanoparticle carrier. In other embodiments, a first therapeutic agent is loaded into / encapsulated by a nanocarrier and a second therapeutic agent is incorporated within an external layer of the nanoparticle carrier. In some embodiments, a therapeutic agent of an immuno-nanoparticle construct can include a STING agonist. The activation of STING, an intracellular receptor residing in the endoplasmic reticulum, can enhance antitumor immunity through the induction of a variety of pro-inflammatory cytokines and chemokines, including type I IFNs. Several natural and synthetic STING agonists have been discovered or developed for use in immunotherapy. Upon binding to CDNs, STING translocates from the ER to the Golgi apparatus and further to the perinuclear microsomes or punctuate structures, which in turn recruit the downstream TANK-binding kinase 1 (TBK1) and the transcription factor interferon regulatory factor 3 Attorney Docket No.11555-011WO1 (IRF3), leading to induction of type I IFNs. In some embodiments, a STING agonist for use in compositions and methods described here can include cyclic dinucleotides (CDNs), such as cyclic dimeric guanosine monophosphate (c-di-GMP or cdGMP), cyclic dimeric adenosine monophosphate (c-di- AMP or cdAMP), and cyclic GMP-AMP (cGAMP, such as 3^3^-cGAMP and 2^3^cGAMP). In some embodiments, CDNs can be chemically modified to improve biostability. An exemplary chemically modified CDN is ADU-S1000, also known as ML RR-S2 CDA. In another embodiment, a STING activating agent can include a small molecule amidobenzimidazole (ABZI) compound. In some embodiments, a STING activating agent can include two symmetry-related ABZI-based compounds linked to form a diABZI compound, in order to enhance both binding to STING and cellular function. In some embodiments, a therapeutic agent of an immuno-nanoparticle construct can include a TLR4 agonist. TLR4 is expressed by cells of the innate immune system, including conventional dendritic cells and macrophages. Triggering via TLR4 induces a signaling cascade that utilizes both the MyD88- and TRIF-dependent pathways, leading to NF-1B and IRF3 / 7 activation, respectively. Various useful TLR4 agonists are known in the art, many of which are analogs or derivatives of endotoxin or lipopolysaccharide (LPS). For example, LPS-derivatives for use as a TLR4 agonist can be made synthetically to provide more control over the structure of the most potent aspect of the LPS, lipid A. Therefore, in some embodiments, the LPS- derivative can include a synthetic lipid A variant, derivative, mimetic or analog. The TLR4 agonist monophosphoryl lipid A (MPLA) has been shown to trigger a strong pro-inflammatory Th1 cytokine response. Thus, in some embodiments, TLR4 agonists can include MPLA, a derivative or analog thereof. MPLA can include either synthetic or naturally derived MPLA. In some embodiments, the TLR4 agonist can include 3d-MPL (i.e.3-O-deacylated monophosphoryl lipid A; also known as 3-de-O-acylated monophosphoryl lipid A or 3-O-desacyl-4^-monophosphoryl lipid A). This derivative of the monophosphoryl lipid A portion of endotoxin has a de-acylated position 3 of the reducing end of glucosamine.3d-MPL can be prepared from a heptoseless mutant of Salmonella minnesota and is chemically similar to lipid A but lacks an acid-labile phosphoryl group and a base-labile acyl group. In some embodiments, TLR4 agonists can include aminoalkyl glucosaminide phosphate compounds (AGPs). AGPs are a monosaccharide mimetic of the lipid A protein of bacterial LPS and have been developed with ether and ester linkages on the acyl chains Attorney Docket No.11555-011WO1 of the compound. Processes for making these compounds are known and disclosed, for example, in WO 2006 / 016997, U.S. Pat. Nos.7,288,640 and 6,113,918, and WO 01 / 90129. Exemplary AGPs for use in a composition described herein can include, but are not limited to, RC-529, CRX-524, CRX-527 CRX-547, CRX-601 and CRX-602. Additional lipid A analogs for use in an immuno-nanoparticle construct described herein can include the water- soluble tri-acyl lipid A, OM-174. TLR4 agonist can also include the synthetic glucopyranosyl lipid A (GLA), a stable emulsion of GLA, or its ammonium salt. In some embodiments, the STING pathway agonist and the TLR4 agonist are present in the lipid-based nanoparticle carrier at a molar ratio of STING pathway agonist:TLR4 agonist of from 0.5:1 to 5:1 (e.g., from 1:1 to 3:1, or from 1:1 to 2.5:1). In some embodiments, the immunomodulatory lipid nanoparticles can additionally or optionally include at least one targeting moiety that is capable of targeting and / or adhering the nanoparticle construct to a cell or tissue of interest. The targeting moiety can comprise any molecule, or complex of molecules, which is / are capable of interacting with an intracellular, cell surface, or extracellular biomarker of the cell. The biomarker can include, for example, a cellular protease, a kinase, a protein, a cell surface receptor, a lipid, and / or fatty acid. Other examples of biomarkers that the targeting moiety can interact with include molecules associated with a particular disease. For example, the biomarkers can include cell surface receptors implicated in cancer development, such as epidermal growth factor receptor and transferrin receptor, or cancer metastasis, such as ^v^3integrin. The targeting moieties can interact with the biomarkers through, for example, non-covalent binding, covalent binding, hydrogen binding, van der Waals forces, ionic bonds, hydrophobic interactions, electrostatic interaction, and / or combinations thereof. The targeting moieties can include, but are not limited to, synthetic compounds, natural compounds or products, macromolecular entities, bioengineered molecules (e.g., polypeptides, lipids, polynucleotides, antibodies, antibody fragments), and small entities (e.g., small molecules, neurotransmitters, substrates, ligands, hormones and elemental compounds). In one example, the targeting moiety can include an antibody, such as a monoclonal antibody, a polyclonal antibody, or a humanized antibody. The antibody can include Fv fragments, single chain Fv (scFv) fragments, Fab^ fragments, F(ab^)2fragments, single domain antibodies, camelized antibodies and other antibody fragments. The antibody can also include multivalent versions of the foregoing antibodies or fragments thereof including monospecific or bispecific antibodies, such as disulfide stabilized Fv fragments, scFv Attorney Docket No.11555-011WO1 tandems ((scFv)2 fragments), diabodies, tribodies or tetrabodies, which typically are covalently linked or otherwise stabilized (i.e., leucine zipper or helix stabilized) scFv fragments; and receptor molecules, which naturally interact with a desired target molecule. Preparation of antibodies can be accomplished by any number of methods for generating antibodies. These methods typically include the step of immunization of animals, such as mice or rabbits, with a desired immunogen (e.g., a desired target molecule or fragment thereof). Once the mammals have been immunized and boosted one or more times with the desired immunogen(s), antibody-producing hybridomas may be prepared and screened according to well-known methods. See, for example, Kuby, Janis, Immunology, Third Edition, pp.131-139, W.H. Freeman & Co. (1997), for a general overview of monoclonal antibody production, that portion of which is incorporated herein by reference. In vitro methods that combine antibody recognition and phage display techniques can also be used to allow one to amplify and select antibodies with very specific binding capabilities. See, for example, Holt, L. J. et al., “The Use of Recombinant Antibodies in Proteomics,” Current Opinion in Biotechnology, 2000, 11:445-449, incorporated herein by reference. These methods typically are much less cumbersome than preparation of hybridomas by traditional monoclonal antibody preparation methods. In some embodiments, phage display technology may be used to generate a targeting moiety specific for a desired target molecule. An immune response to a selected immunogen is elicited in an animal (such as a mouse, rabbit, goat or other animal) and the response is boosted to expand the immunogen-specific B-cell population. Messenger RNA is isolated from those B-cells, or optionally a monoclonal or polyclonal hybridoma population. The mRNA is reverse-transcribed by known methods using either a poly-A primer or murine immunoglobulin-specific primer(s), typically specific to sequences adjacent to the desired VH and VL chains, to yield cDNA. The desired VH and VL chains are amplified by polymerase chain reaction (PCR) typically using VH and VL specific primer sets, and are ligated together, separated by a linker. VH and VL specific primer sets are commercially available, for instance from Stratagene, Inc. of La Jolla, Calif. Assembled VH- linker-VL product (encoding a scFv fragment) is selected for and amplified by PCR. Restriction sites are introduced into the ends of the VH-linker-VLproduct by PCR with primers including restriction sites and the scFv fragment is inserted into a suitable expression vector (typically a plasmid) for phage display. Other fragments, such as a Fab^ fragment, may be cloned into phage display vectors for surface expression on phage particles. The phage may be any phage, such as lambda, but typically is a filamentous Attorney Docket No.11555-011WO1 phage, such as Fd and M13, typically M13. In phage display vectors, the VH-linker-VL sequence is cloned into a phage surface protein (for M13, the surface proteins g3p (pIII) or g8p, most typically g3p). Phage display systems also include phagemid systems, which are based on a phagemid plasmid vector containing the phage surface protein genes (for example, g3p and g8p of M13) and the phage origin of replication. To produce phage particles, cells containing the phagemid are rescued with helper phage providing the remaining proteins needed for the generation of phage. Only the phagemid vector is packaged in the resulting phage particles because replication of the phagemid is grossly favored over replication of the helper phage DNA. Phagemid packaging systems for production of antibodies are commercially available. One example of a commercially available phagemid packaging system that also permits production of soluble ScFv fragments in bacterial cells is the Recombinant Phage Antibody System (RPAS), commercially available from Amersham Pharmacia Biotech, Inc. of Piscataway, N.J. and the pSKAN Phagemid Display System, commercially available from MoBiTec, LLC of Marco Island, Fla. Phage display systems, their construction, and screening methods are described in detail in, among others, U.S. Pat. Nos.5,702,892, 5,750,373, 5,821,047 and 6,127,132, each of which is incorporated herein by reference in their entirety. The targeting moiety need not originate from a biological source. The targeting moiety may, for example, be screened from a combinatorial library of synthetic peptides. One such method is described in U.S. Pat. No.5,948,635, incorporated herein by reference, which described the production of phagemid libraries having random amino acid insertions in the pIII gene of M13. These phage may be clonally amplified by affinity selection as described above. The immunogens used to prepare targeting moieties having a desired specificity will generally be the target molecule, or a fragment or derivative thereof. Such immunogens may be isolated from a source where they are naturally occurring or may be synthesized using methods known in the art. For example, peptide chains may be synthesized by 1- ethyl-3-[dimethylaminoproply]carbodiimide (EDC)-catalyzed condensation of amine and carboxyl groups. In certain embodiments, the immunogen may be linked to a carrier bead or protein. For example, the carrier may be a functionalized bead such as SASRIN resin commercially available from Bachem, King of Prussia, Pa. or a protein such as keyhole limpet hemocyanin (KLH) or bovine serum albumin (BSA). The immunogen may be attached directly to the carrier or may be associated with the carrier via a linker, such as a Attorney Docket No.11555-011WO1 non-immunogenic synthetic linker (for example, a polyethylene glycol (PEG) residue, amino caproic acid or derivatives thereof) or a random, or semi-random polypeptide. In certain embodiments, it may be desirable to mutate the binding region of the polypeptide targeting moiety and select for a targeting moiety with superior binding characteristics as compared to the un-mutated targeting moiety. This may be accomplished by any standard mutagenesis technique, such as by PCR with Taq polymerase under conditions that cause errors. In such a case, the PCR primers could be used to amplify scFv- encoding sequences of phagemid plasmids under conditions that would cause mutations. The PCR product may then be cloned into a phagemid vector and screened for the desired specificity, as described above. In other embodiments, the targeting moieties may be modified to make them more resistant to cleavage by proteases. For example, the stability of targeting moiety comprising a polypeptide may be increased by substituting one or more of the naturally occurring amino acids in the (L) configuration with D-amino acids. In various embodiments, at least 1%, 5%, 10%, 20%, 50%, 80%, 90% or 100% of the amino acid residues of targeting moiety may be of the D configuration. The switch from L to D amino acids neutralizes the digestion capabilities of many of the ubiquitous peptidases found in the digestive tract. Alternatively, enhanced stability of a targeting moiety comprising a peptide bond may be achieved by the introduction of modifications of the traditional peptide linkages. For example, the introduction of a cyclic ring within the polypeptide backbone may confer enhanced stability in order to circumvent the effect of many proteolytic enzymes known to digest polypeptides in the stomach or other digestive organs and in serum. In still other embodiments, enhanced stability of a targeting moiety may be achieved by intercalating one or more dextrorotatory amino acids (such as, dextrorotatory phenylalanine or dextrorotatory tryptophan) between the amino acids of targeting moiety. In exemplary embodiments, such modifications increase the protease resistance of a targeting moiety without affecting the activity or specificity of the interaction with a desired target molecule. In certain embodiments, a targeting moiety as described herein may comprise a homing peptide, which selectively directs the nanoparticle to a targeted cell. Homing peptides for a targeted cell can be identified using various methods well known in the art. Many laboratories have identified the homing peptides that are selective for cells of the vasculature of brain, kidney, lung, skin, pancreas, intestine, uterus, adrenal gland, retina, muscle, prostate, or tumors. See, for example, Samoylova et al., 1999, Muscle Nerve, 22:460; Pasqualini et al., 1996 Nature, 380:364; Koivunen et al., 1995, Biotechnology, Attorney Docket No.11555-011WO1 13:265; Pasqualini et al., 1995, J. Cell Biol., 130:1189; Pasqualini et al., 1996, Mole. Psych., 1:421, 423; Rajotte et al., 1998, J. Clin. Invest., 102:430; Rajotte et al., 1999, J. Biol. Chem., 274:11593. See, also, U.S. Pat. Nos.5,622,6999; 6,068,829; 6,174,687; 6,180,084; 6,232,287; 6,296,832; 6,303,573; and 6,306,365. Phage display technology provides a means for expressing a diverse population of random or selectively randomized peptides. Various methods of phage display and methods for producing diverse populations of peptides are well known in the art. For example, methods for preparing diverse populations of binding domains on the surface of a phage have been described in U.S. Pat. No.5,223,409. In particular, phage vectors useful for producing a phage display library as well as methods for selecting potential binding domains and producing randomly or selectively mutated binding domains are also provided in U.S. Pat. No.5,223,409. Similarly, methods of producing phage peptide display libraries, including vectors and methods of diversifying the population of peptides that are expressed, are also described in Smith et al., 1993, Meth. Enzymol., 217:228-257, Scott et al., Science, 249:386-390, and two PCT publications WO 91 / 07141 and WO 91 / 07149. Phage display technology can be particularly powerful when used, for example, with a codon-based mutagenesis method, which can be used to produce random peptides or randomly or desirably biased peptides (see, e.g., U.S. Pat. No.5,264,563). These or other well-known methods can be used to produce a phage display library, which can be subjected to the in vivo phage display method in order to identify a peptide that homes to one or a few selected tissues. In vitro screening of phage libraries has previously been used to identify peptides that bind to antibodies or cell surface receptors (see, e.g., Smith, et al., 1993, Meth. Enzymol., 217:228-257). For example, in vitro screening of phage peptide display libraries has been used to identify novel peptides that specifically bind to integrin adhesion receptors (see, e.g., Koivunen et al., 1994, J. Cell Biol.124:373-380), and to the human urokinase receptor (Goodson, et al., 1994, Proc. Natl. Acad. Sci., USA 91:7129-7133). In certain embodiments, the targeting moiety may comprise a receptor molecule, including, for example, receptors, which naturally recognize a specific desired molecule of a target cell. Such receptor molecules include receptors that have been modified to increase their specificity of interaction with a target molecule, receptors that have been modified to interact with a desired target molecule not naturally recognized by the receptor, and fragments of such receptors (see, e.g., Skerra, 2000, J. Molecular Recognition, 13:167-187). A preferred receptor is a chemokine receptor. Exemplary chemokine receptors have been Attorney Docket No.11555-011WO1 described in, for example, Lapidot et al, 2002, Exp Hematol, 30:973-81 and Onuffer et al, 2002, Trends Pharmacol Sci, 23:459-67. In still other embodiments, the targeting moiety may comprise a ligand molecule, including, for example, ligands which naturally recognize a specific desired receptor of a target cell, such as a Transferrin (Tf) ligand. Such ligand molecules include ligands that have been modified to increase their specificity of interaction with a target receptor, ligands that have been modified to interact with a desired receptor not naturally recognized by the ligand, and fragments of such ligands. In other embodiments, the targeting moiety may comprise an aptamer. Aptamers are oligonucleotides that are selected to bind specifically to a desired molecular structure of the target cell. Aptamers typically are the products of an affinity selection process similar to the affinity selection of phage display (also known as in vitro molecular evolution). The process involves performing several tandem iterations of affinity separation, e.g., using a solid support to which the diseased immunogen is bound, followed by polymerase chain reaction (PCR) to amplify nucleic acids that bound to the immunogens. Each round of affinity separation thus enriches the nucleic acid population for molecules that successfully bind the desired immunogen. In this manner, a random pool of nucleic acids may be “educated” to yield aptamers that specifically bind target molecules. Aptamers typically are RNA, but may be DNA or analogs or derivatives thereof, such as, without limitation, peptide nucleic acids (PNAs) and phosphorothioate nucleic acids. In yet other embodiments, the targeting moiety may be a peptidomimetic. By employing, for example, scanning mutagenesis to map the amino acid residues of a protein, which is involved in binding other proteins, peptidomimetic compounds can be generated which mimic those residues which facilitate the interaction. Such mimetics may then be used as a targeting moiety to deliver the composition to a target cell. For instance, non- hydrolyzable peptide analogs of such resides can be generated using benzodiazepine (e.g., see Freidinger et al. in Peptides: Chemistry and Biology, G. R. Marshall ed., ESCOM Publisher: Leiden, Netherlands, 1988), azepine (e.g., see Huffman et al. in Peptides: Chemistry and Biology, G. R. Marshall ed., ESCOM Publisher: Leiden, Netherlands, 1988), substituted gamma lactam rings (Garvey et al. in Peptides: Chemistry and Biology, G. R. Marshall ed., ESCOM Publisher: Leiden, Netherlands, 1988), keto-methylene pseudopeptides (Ewenson et al., 1986, J Med Chem 29:295; and Ewenson et al., in Peptides: Structure and Function (Proceedings of the 9th American Peptide Symposium) Pierce Chemical Co. Rockland, Ill., 1985), b-turn dipeptide cores (Nagai et al., 1985, Attorney Docket No.11555-011WO1 Tetrahedron Lett 26:647; and Sato et al., 1986, J Chem Soc Perkin Trans 1:1231), and ^- aminoalcohols (Gordon et al., 1985, Biochem Biophys Res Cummun 126:419; and Dann et al., 1986, Biochem Biophys Res Commun 134:71). The targeting moiety may be attached directly to the immunomodulatory lipid nanoparticles. In one embodiment, a targeting moiety may be conjugated onto an amine- functionalized mesoporous silica nanocore nanoparticle via maleimide chemistry. In some embodiments, the targeting moiety may be associated with or coupled to the nanoparticles using a linker. The linker can be of any suitable length and contain any suitable number of atoms and / or subunits. The linker can include one or combination of chemical and / or biological moieties. Examples of chemical moieties can include alkyl groups, methylene carbon chains, ether, polyether, alkyl amide linkers, alkenyl chains, alkynyl chains, disulfide groups, and polymers, such as poly(ethylene glycol) (PEG), functionalized PEG, PEG-chelant polymers, dendritic polymers, and combinations thereof. Examples of biological moieties can include peptides, modified peptides, streptavidin-biotin or avidin- biotin, polyaminoacids (e.g., polylysine), polysaccharides, glycosaminoglycans, oligonucleotides, phospholipid derivatives, and combinations thereof. In some embodiments, the immunomodulatory lipid nanoparticles can include multiple types of targeting moieties and the spacing and location of the targeting moieties on each nanoparticle construct can be controlled to facilitate delivery, targeting, and / or therapeutic efficacy of the co-loaded therapeutic cargo. In some embodiments, the compositions described herein further comprise one or more tumor antigens. The tumor antigens can comprise any suitable tumor antigen, such as one or more tumor antigenic peptides, a nucleic acid encoding for a tumor antigen, or any combination thereof. In some embodiments, the compositions described herein further comprise a tumor lysate or an extract thereof. In some cases, the tumor lysate can be obtained from a biopsy or tissue sample collected from the subject. The compositions described herein can be used to treat and / or prevent cancer in a subject. In some embodiments, the composition is administered locally to the subject. For example, the composition can be administered by subcutaneous injection, intradermal injection, or intramuscular injection. Upon administration, the population of immunomodulatory lipid nanoparticles can preferentially accumulate in a lymph node in the subject. In certain of these embodiments, the composition further comprises one or more Attorney Docket No.11555-011WO1 tumor antigens and / or a tumor lysate or an extract thereof. In these embodiments, the composition can induce an immune response in the subject targeting a tumor and / or cancer cells. In some embodiments, the immunomodulatory lipid nanoparticles can further comprise one or more targeting moieties are covalently linked to the immunomodulatory lipid nanoparticles. The one or more targeting moieties can comprise any suitable moieties (e.g., peptides, nucleic acids such as aptamers, etc.) that bind to or otherwise target or recognize targets overexpressed in tumor cells and / or present in the tumor microenvironment. In some examples, the one or more targeting moieties are selected from the group consisting of a peptide that binds to fibrin-fibronectin extracellular matrix, a peptide that binds to P-selectin, a peptide that binds to ^^^3 integrins, a peptide that binds to epidermal growth factor receptor (EGFR), or a combination thereof. In some of these embodiments, the composition is administered systemically to the subject. In certain embodiments, the composition is administered by intravenous injection. These compositions can be used to treat and / or prevent cancer metastasis in a subject. In some embodiments, the cancer metastasis comprises a dormant metastasis. In some embodiments, the cancer metastasis comprises an aggressive metastasis. When used to treat cancer, the immunomodulatory lipid nanoparticles can be administered to a subject who has been diagnosed with cancer, in order to stimulate or increase an interferon ^-driven anti-tumor immune response against the subject's cancer cells. As is known to those skilled in the art, there are a variety of methods of identifying (i.e., diagnosing) a subject who has cancer. For example, diagnosis of cancer can include one or more of a physical exam, laboratory tests, imaging analysis, and biopsy. After cancer is diagnosed, a variety of tests may be carried out to look for specific features characteristic of different types and or the extent of cancer in the subject. These tests include, but are not limited to, bone scans, X-rays, immunophenotyping, flow cytometry, and fluorescence in situ hybridization testing. For example, typical methods of diagnosing triple-negative breast cancer can include, but are not limited to, a physical exam, digital mammogram, breast MRI, breast ultrasound, stereotactic core and / or open tumor biopsy, as well as lab tests to determine if the tumor tissue expresses estrogen, progesterone, and HER-2 / neu or not. Alternately, the immunomodulatory lipid nanoparticles can be administered to a subject who has not been diagnosed with cancer as a means of preventing or decreasing the risk or likelihood of cancer development. In some embodiments, the subject being treated using compositions described herein has been characterized as being a subject having a high Attorney Docket No.11555-011WO1 or increased risk of developing cancer. Subjects can be characterized as being at high or increased risk of developing cancer as a result of, for example, family history, genetic testing, or high exposure to cancer-causing environmental conditions. “Cancer” or “malignancy” are used as synonymous terms and refer to any of a number of diseases that are characterized by uncontrolled, abnormal proliferation of cells, the ability of affected cells to spread locally or through the bloodstream and lymphatic system to other parts of the body (i.e., metastasize) as well as any of a number of characteristic structural and / or molecular features. A “cancer cell” refers to a cell undergoing early, intermediate or advanced stages of multi-step neoplastic progression. The features of early, intermediate and advanced stages of neoplastic progression have been described using microscopy. Cancer cells at each of the three stages of neoplastic progression generally have abnormal karyotypes, including translocations, inversion, deletions, isochromosomes, monosomies, and extra chromosomes. Cancer cells include “hyperplastic cells,” that is, cells in the early stages of malignant progression, “dysplastic cells,” that is, cells in the intermediate stages of neoplastic progression, and “neoplastic cells,” that is, cells in the advanced stages of neoplastic progression. The cancers treated by a method described herein can include the following: leukemias, such as but not limited to, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemias, such as, myeloblastic, promyelocytic, myelomonocytic, monocytic, and erythroleukemia leukemias and myelodysplastic syndrome; chronic leukemias, such as but not limited to, chronic myelocytic (granulocytic) leukemia, chronic lymphocytic leukemia, hairy cell leukemia; polycythemia vera; lymphomas such as but not limited to Hodgkin's disease, non-Hodgkin's disease; multiple myelomas such as but not limited to smoldering multiple myeloma, nonsecretory myeloma, osteosclerotic myeloma, plasma cell leukemia, solitary plasmacytoma and extramedullary plasmacytoma; Waldenstrom's macroglobulinemia; monoclonal gammopathy of undetermined significance; benign monoclonal gammopathy; heavy chain disease; bone and connective tissue sarcomas such as but not limited to bone sarcoma, osteosarcoma, chondrosarcoma, Ewing's sarcoma, malignant giant cell tumor, fibrosarcoma of bone, chordoma, periosteal sarcoma, soft-tissue sarcomas, angiosarcoma (hemangiosarcoma), fibrosarcoma, Kaposi's sarcoma, leiomyosarcoma, liposarcoma, lymphangiosarcoma, neurilemmoma, rhabdomyosarcoma, synovial sarcoma; brain tumors such as but not limited to, glioma, astrocytoma, glioblastoma, brain stem glioma, ependymoma, oligodendroglioma, nonglial tumor, acoustic neurinoma, craniopharyngioma, medulloblastoma, meningioma, pineocytoma, Attorney Docket No.11555-011WO1 pineoblastoma, primary brain lymphoma; breast cancer including but not limited to ductal carcinoma, adenocarcinoma, lobular (small cell) carcinoma, intraductal carcinoma, medullary breast cancer, mucinous breast cancer, tubular breast cancer, papillary breast cancer, Paget's disease, and inflammatory breast cancer; adrenal cancer such as but not limited to pheochromocytoma and adrenocortical carcinoma; thyroid cancer such as but not limited to papillary or follicular thyroid cancer, medullary thyroid cancer and anaplastic thyroid cancer; pancreatic cancer such as but not limited to, insulinoma, gastrinoma, glucagonoma, vipoma, somatostatin-secreting tumor, and carcinoid or islet cell tumor; pituitary cancers such as but limited to Cushing's disease, prolactin-secreting tumor, acromegaly, and diabetes insipius; eye cancers such as but not limited to ocular melanoma such as iris melanoma, choroidal melanoma, and cilliary body melanoma, and retinoblastoma; vaginal cancers such as squamous cell carcinoma, adenocarcinoma, and melanoma; vulvar cancer such as squamous cell carcinoma, melanoma, adenocarcinoma, basal cell carcinoma, sarcoma, and Paget's disease; cervical cancers such as but not limited to, squamous cell carcinoma, and adenocarcinoma; uterine cancers such as but not limited to endometrial carcinoma and uterine sarcoma; ovarian cancers such as but not limited to, ovarian epithelial carcinoma, borderline tumor, germ cell tumor, fallopian tube cancer, and stromal tumor; esophageal cancers such as but not limited to, squamous cancer, adenocarcinoma, adenoid cystic carcinoma, mucoepidermoid carcinoma, adenosquamous carcinoma, sarcoma, melanoma, plasmacytoma, verrucous carcinoma, and oat cell (small cell) carcinoma; stomach cancers such as but not limited to, adenocarcinoma, fungating (polypoid), ulcerating, superficial spreading, diffusely spreading, malignant lymphoma, liposarcoma, fibrosarcoma, and carcinosarcoma; colon cancers; rectal cancers; liver cancers such as but not limited to hepatocellular carcinoma and hepatoblastoma; gallbladder cancers such as adenocarcinoma; cholangiocarcinomas such as but not limited to papillary, nodular, and diffuse; lung cancers such as non-small cell lung cancer, squamous cell carcinoma (epidermoid carcinoma), adenocarcinoma, large-cell carcinoma and small-cell lung cancer; testicular cancers such as but not limited to germinal tumor, seminoma, anaplastic, classic (typical), spermatocytic, nonseminoma, embryonal carcinoma, teratoma carcinoma, choriocarcinoma (yolk-sac tumor), prostate cancers such as but not limited to, prostatic intraepithelial neoplasia, adenocarcinoma, leiomyosarcoma, and rhabdomyosarcoma; penal cancers; oral cancers such as but not limited to squamous cell carcinoma; basal cancers; salivary gland cancers such as but not limited to adenocarcinoma, mucoepidermoid carcinoma, and adenoidcystic carcinoma; pharynx cancers such as but not limited to Attorney Docket No.11555-011WO1 squamous cell cancer, and verrucous; skin cancers such as but not limited to, basal cell carcinoma, squamous cell carcinoma and melanoma, superficial spreading melanoma, nodular melanoma, lentigo malignant melanoma, acral lentiginous melanoma; kidney cancers such as but not limited to renal cell carcinoma, adenocarcinoma, hypemephroma, fibrosarcoma, transitional cell cancer (renal pelvis and / or uterer); Wilms' tumor; bladder cancers such as but not limited to transitional cell carcinoma, squamous cell cancer, adenocarcinoma, carcinosarcoma. In addition, cancers include myxosarcoma, osteogenic sarcoma, endotheliosarcoma, lymphangioendotheliosarcoma, mesothelioma, synovioma, hemangioblastoma, epithelial carcinoma, cystadenocarcinoma, bronchogenic carcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma and papillary adenocarcinomas (for a review of such disorders, see Fishman et al., 1985, Medicine, 2d Ed., J. B. Lippincott Co., Philadelphia and Murphy et al., 1997, Informed Decisions: The Complete Book of Cancer Diagnosis, Treatment, and Recovery, Viking Penguin, Penguin Books U.S.A., Inc., United States of America). In certain embodiments, cancers treated in accordance with a method described herein include breast cancers, lung cancer, and melanoma. In some embodiments, a method of treating cancer described herein can include administering an additional therapeutic or cancer therapy to the subject. A “cancer therapeutic” or “cancer therapy”, as used herein, can include any agent or treatment regimen that is capable of negatively affecting cancer in an animal, for example, by killing cancer cells, inducing apoptosis in cancer cells, reducing the growth rate of cancer cells, reducing the incidence or number of metastases, reducing tumor size, inhibiting tumor growth, reducing the blood supply to a tumor or cancer cells, promoting an immune response against cancer cells or a tumor, preventing or inhibiting the progression of cancer, or increasing the lifespan of an animal with cancer. Cancer therapeutics can include one or more therapies such as, but not limited to, chemotherapies, radiation therapies, hormonal therapies, and / or biological therapies / immunotherapies. A reduction, for example, in cancer volume, growth, migration, and / or dispersal in a subject may be indicative of the efficacy of a given therapy. In some embodiments, the method can include the step of administering a therapeutically effective amount of an additional anticancer therapeutic agent to the subject. Additional anticancer therapeutic agents can be in the form of biologically active ligands, small molecules, peptides, polypeptides, proteins, DNA fragments, DNA plasmids, interfering RNA molecules, such as siRNAs, oligonucleotides, and DNA encoding for Attorney Docket No.11555-011WO1 shRNA. In some embodiments, cytotoxic compounds are included in an anticancer agent described herein. Cytotoxic compounds include small-molecule drugs such as doxorubicin, methotrexate, vincristine, and pyrimidine and purine analogs, referred to herein as antitumor agents. In particular embodiments, an additional anticancer therapeutic agent can include a corticosteroid such as but not limited to prednisone. The additional anticancer therapeutic agent can include an anticancer or an antiproliferative agent that exerts an antineoplastic, chemotherapeutic, antiviral, antimitotic, antitumorgenic, and / or immunotherapeutic effects, e.g., prevent the development, maturation, or spread of neoplastic cells, directly on the tumor cell, e.g., by cytostatic or cytocidal effects, and not indirectly through mechanisms such as biological response modification. There are large numbers of anti-proliferative agent agents available in commercial use, in clinical evaluation and in pre-clinical development. For convenience of discussion, anti-proliferative agents are classified into the following classes, subtypes and species: ACE inhibitors, alkylating agents, angiogenesis inhibitors, angiostatin, anthracyclines / DNA intercalators, anti-cancer antibiotics or antibiotic-type agents, antimetabolites, antimetastatic compounds, asparaginases, bisphosphonates, cGMP phosphodiesterase inhibitors, calcium carbonate, cyclooxygenase-2 inhibitors, DHA derivatives, DNA topoisomerase, endostatin, epipodophylotoxins, genistein, hormonal anticancer agents, hydrophilic bile acids (URSO), immunomodulators or immunological agents, integrin antagonists, interferon antagonists or agents, MMP inhibitors, miscellaneous antineoplastic agents, monoclonal antibodies, nitrosoureas, NSAIDs, ornithine decarboxylase inhibitors, pBATTs, radio / chemo sensitizers / protectors, retinoids, selective inhibitors of proliferation and migration of endothelial cells, selenium, stromelysin inhibitors, taxanes, vaccines, and vinca alkaloids. The major categories that some anti-proliferative agents fall into include antimetabolite agents, alkylating agents, antibiotic-type agents, hormonal anticancer agents, immunological agents, interferon-type agents, and a category of miscellaneous antineoplastic agents. Some anti-proliferative agents operate through multiple or unknown mechanisms and can thus be classified into more than one category. Examples of anticancer therapeutic agents that can be administered in combination with an immuno-nanoparticle construct described herein include Taxol, Adriamycin, dactinomycin, bleomycin, vinblastine, cisplatin, acivicin; aclarubicin; acodazole hydrochloride; acronine; adozelesin; aldesleukin; altretamine; ambomycin; ametantrone acetate; aminoglutethimide; amsacrine; anastrozole; anthramycin; asparaginase; asperlin; Attorney Docket No.11555-011WO1 azacitidine; azetepa; azotomycin; batimastat; benzodepa; bicalutamide; bisantrene hydrochloride; bisnafide dimesylate; bizelesin; bleomycin sulfate; brequinar sodium; bropirimine; busulfan; cactinomycin; calusterone; caracemide; carbetimer; carboplatin; carmustine; carubicin hydrochloride; carzelesin; cedefingol; chlorambucil; cirolemycin; cladribine; crisnatol mesylate; cyclophosphamide; cytarabine; dacarbazine; daunorubicin hydrochloride; decitabine; dexormaplatin; dezaguanine; dezaguanine mesylate; diaziquone; doxorubicin; doxorubicin hydrochloride; droloxifene; droloxifene citrate; dromostanolone propionate; duazomycin; edatrexate; eflomithine hydrochloride; elsamitrucin; enloplatin; enpromate; epipropidine; epirubicin hydrochloride; erbulozole; esorubicin hydrochloride; estramustine; estramustine phosphate sodium; etanidazole; etoposide; etoposide phosphate; etoprine; fadrozole hydrochloride; fazarabine; fenretinide; floxuridine; fludarabine phosphate; fluorouracil; fluorocitabine; fosquidone; fostriecin sodium; gemcitabine; gemcitabine hydrochloride; hydroxyurea; idarubicin hydrochloride; ifosfamide; ilmofosine; interleukin II (including recombinant interleukin II, or rIL2), interferon alfa-2a; interferon alfa-2b; interferon alfa-n1; interferon alfa-n3; interferon beta-I a; interferon gamma-I b; iproplatin; irinotecan hydrochloride; lanreotide acetate; letrozole; leuprolide acetate; liarozole hydrochloride; lometrexol sodium; lomustine; losoxantrone hydrochloride; masoprocol; maytansine; mechlorethamine hydrochloride; megestrol acetate; melengestrol acetate; melphalan; menogaril; mercaptopurine; methotrexate; methotrexate sodium; metoprine; meturedepa; mitindomide; mitocarcin; mitocromin; mitogillin; mitomalcin; mitomycin; mitosper; mitotane; mitoxantrone hydrochloride; mycophenolic acid; nocodazole; nogalamycin; ormaplatin; oxisuran; pegaspargase; peliomycin; pentamustine; peplomycin sulfate; perfosfamide; pipobroman; piposulfan; piroxantrone hydrochloride; plicamycin; plomestane; porfimer sodium; porfiromycin; prednimustine; procarbazine hydrochloride; puromycin; puromycin hydrochloride; pyrazofurin; riboprine; rogletimide; safingol; safingol hydrochloride; semustine; simtrazene; sparfosate sodium; sparsomycin; spirogermanium hydrochloride; spiromustine; spiroplatin; streptonigrin; streptozocin; sulofenur; talisomycin; tecogalan sodium; tegafur; temozolomide, teloxantrone hydrochloride; temoporfin; teniposide; teroxirone; testolactone; thiamiprine; thioguanine; thiotepa; tiazofurin; tirapazamine; toremifene citrate; trestolone acetate; triciribine phosphate; trimetrexate; trimetrexate glucuronate; triptorelin; tubulozole hydrochloride; uracil mustard; uredepa; vapreotide; verteporfin; vinblastine sulfate; vincristine sulfate; vindesine; vindesine sulfate; vinepidine sulfate; vinglycinate sulfate; vinleurosine sulfate; vinorelbine tartrate; vinrosidine sulfate; vinzolidine sulfate; vorozole; zeniplatin; zinostatin; Attorney Docket No.11555-011WO1 zorubicin hydrochloride. In some embodiments, the anti-cancer therapy administered to the subject in addition to the immuno-nanoparticle constructs can include the cancer ablation therapy. Ablating the cancer can be accomplished using a method selected from the group consisting of cryoablation, thermal ablation, radiotherapy, chemotherapy, radiofrequency ablation, electroporation, alcohol ablation, high intensity focused ultrasound, photodynamic therapy, administration of monoclonal antibodies, immunotherapy, and administration of immunotoxins. Appropriate surgeries for treating other types of cancer are known to those skilled in the art. In some embodiments, ablating the cancer includes immunotherapy of the cancer. Cancer immunotherapy is based on therapeutic interventions that aim to utilize the immune system to combat malignant diseases. It can be divided into unspecific approaches and specific approaches. Unspecific cancer immunotherapy aims at activating parts of the immune system generally, such as treatment with specific cytokines known to be effective in cancer immunotherapy (e.g., IL-2, interferon's, cytokine inducers). In contrast, specific cancer immunotherapy is based on certain antigens that are preferentially or solely expressed on cancer cells or predominantly expressed by other cells in the context of malignant disease (usually in vicinity of the tumor site). Specific cancer immunotherapy can be grouped into passive and active approaches. In passive specific cancer immunotherapy substances with specificity for certain structures related to cancer that are derived from components of the immune system are administered to the patient. The most prominent and successful approaches are treatments with humanized or mouse / human chimeric monoclonal antibodies against defined cancer associated structures (such as Trastuzumab, Rituximab, Cetuximab, Bevacizumab, Alemtuzumab). The pharmacologically active substance exerts is activity as long as a sufficient concentration is present in the body of the patient, therefore administrations have to be repeated based on pharmacokinetic and pharmacodynamic considerations. On the other hand, active specific cancer immunotherapy aims at antigen-specific stimulation of the patient's immune system to recognize and destroy cancer cells. Active specific cancer immunotherapy therefore, in general, is a therapeutic vaccination approach. There are many types of cancer vaccine approaches being pursued, such as vaccination with autologous or allogeneic whole tumor cells (in most cases genetically modified for better immune recognition), tumor cell lysates, whole tumor associated antigens (produced by means of genetic engineering or by chemical synthesis), peptides derived from protein Attorney Docket No.11555-011WO1 antigens, DNA vaccines encoding for tumor associated antigens, surrogates of tumor antigens such as anti-idiotypic antibodies used as vaccine antigens, and the like. These manifold approaches are usually administered together with appropriate vaccine adjuvants and other immunomodulators in order to elicit a quantitatively and qualitatively sufficient immune response (many novel vaccine adjuvant approaches are being pursued in parallel with the development of cancer vaccines). Another set of cancer vaccine approaches rely on manipulating dendritic cells (DC) as the most important antigen presenting cell of the immune system. For example, loading with tumor antigens or tumor cell lysates, transfection with genes encoding for tumor antigens and in-vivo targeting are suitable immunotherapies that can be used together with the virus or virus-like particles of the invention for cancer treatment. In some embodiments, ablating the cancer includes administering a therapeutically effective amount of radiotherapy (RT) to the subject. In some embodiments, RT is administered prior to administration of the immuno-nanoparticle construct. Radiotherapy uses high-energy rays to treat disease, usually x-rays and similar rays (such as electrons). Radiotherapy administered to a subject can include both external and internal. External radiotherapy (or external beam radiation) aims high-energy x-rays at the tumor site including in some cases the peri-tumor margin. External radiotherapy typically includes the use of a linear accelerator (e.g., a Varian 2100C linear accelerator). External radiation therapy can include three-dimensional conformal radiation therapy (3D-CRT), image guided radiation therapy (IGRT), intensity modulated radiation therapy (IMRT), helical-tomotherapy, photon beam radiation therapy, proton beam radiation therapy, stereotactic radiosurgery and / or sterotactic body radiation therapy (SBRT). Internal radiotherapy (brachytherapy) involves having radioactive material placed inside the body and allows a higher dose of radiation in a smaller area than might be possible with external radiation treatment. It uses a radiation source that is usually sealed in an implant. Exemplary implants include pellets, seeds, ribbons, wires, needles, capsules, balloons, or tubes. Implants are placed in your body, very close to or inside the tumor. Internal radiotherapy can include intracavitary or interstitial radiation. During intracavitary radiation, the radioactive source is placed in a body cavity (space), such as the uterus. With interstitial radiation, the implants are placed in or near the tumor, but not in a body cavity. In some embodiments, an immune checkpoint inhibitor can be further administered to eradicate suppressive regulatory T cells prior to RT. Exemplary checkpoint inhibitors can include CTLA4, 4-1BB and PD-1 / PDL-1 inhibitors. The cytotoxic T-lymphocyte-associated Attorney Docket No.11555-011WO1 antigen 4 (CTLA-4) and programmed death 1 (PD-1) immune checkpoints are negative regulators of T-cell immune function and inhibition of these targets, results in increased activation of the immune system. Therefore, in some embodiments, a checkpoint inhibitor administered to a subject can include a CTLA-4, 4-1BB and / or PD-1 inhibitor. For example, Ipilimumab, an inhibitor of CTLA-4, is approved for the treatment of advanced or unresectable melanoma. Nivolumab and pembrolizumab, both PD-1 inhibitors, are approved to treat patients with advanced or metastatic melanoma and patients with metastatic, refractory non-small cell lung cancer. In addition, the combination of ipilimumab and nivolumab has been approved in patients with BRAF WT metastatic or unresectable melanoma. In some embodiments, an immune checkpoint agonistic agent, such as an OX40 agonistic agent, can be further administered can be administered promote immune activation of cytotoxic T-cells. In another example, immuno-nanoparticle constructs described herein can be administered in combination with a PD-L1 inhibitor and an OX40 agonist. When used in vivo, the immunomodulatory lipid nanoparticles and / or additional anti-cancer therapeutic agents described herein can be administered as a pharmaceutical composition, comprising a mixture, and a pharmaceutically acceptable carrier. The anti- cancer virus particles may be present in a pharmaceutical composition in an amount from 0.001 to 99.9 wt %, more preferably from about 0.01 to 99 wt %, and even more preferably from 0.1 to 95 wt %. For parenteral administration, immunomodulatory lipid nanoparticles can be administered as injectable dosages of a solution or suspension of the substance in a physiologically acceptable diluent with a pharmaceutical carrier that can be a sterile liquid such as water oils, saline, glycerol, or ethanol. Additionally, auxiliary substances, such as wetting or emulsifying agents, surfactants, pH buffering substances and the like can be present in compositions. Other components of pharmaceutical compositions are those of petroleum, animal, vegetable, or synthetic origin, for example, peanut oil, soybean oil, and mineral oil. In general, glycols such as propylene glycol or polyethylene glycol are preferred liquid carriers, particularly for injectable solutions. The pharmaceutical compositions can also include, depending on the formulation desired, pharmaceutically-acceptable, non-toxic carriers or diluents, which are defined as vehicles commonly used to formulate pharmaceutical compositions for animal or human administration. The diluent is selected so as not to affect the biological activity of the combination. Examples of such diluents are distilled water, physiological phosphate- Attorney Docket No.11555-011WO1 buffered saline, Ringer's solutions, dextrose solution, and Hank's solution. In addition, the pharmaceutical composition or formulation may also include other carriers, adjuvants, or nontoxic, nontherapeutic, non-immunogenic stabilizers and the like. Suitable pharmaceutically acceptable carriers may contain inert ingredients which do not unduly inhibit the biological activity of the compounds. The pharmaceutically acceptable carriers should be biocompatible, e.g., non-toxic, non-inflammatory, non- immunogenic and devoid of other undesired reactions upon the administration to a subject. Standard pharmaceutical formulation techniques can be employed, such as those described in Remington's Pharmaceutical Sciences, ibid. Suitable pharmaceutical carriers for parenteral administration include, for example, sterile water, physiological saline, bacteriostatic saline (saline containing about 0.9% mg / ml benzyl alcohol), phosphate- buffered saline, Hank's solution, Ringer's-lactate and the like. Methods for encapsulating compositions (such as in a coating of hard gelatin or cyclodextran) are known in the art (Baker, et al., “Controlled Release of Biological Active Agents”, John Wiley and Sons, 1986). A pharmaceutically acceptable carrier for a pharmaceutical composition can also include delivery systems known to the art for entraining or encapsulating drugs, such as anticancer drugs. In some embodiments, the disclosed compounds can be employed with such delivery systems including, for example, liposomes, nanoparticles, nanospheres, nanodiscs, dendrimers, and the like. See, for example Farokhzad, O. C., Jon, S., Khademhosseini, A., Tran, T. N., Lavan, D. A., and Langer, R. (2004). “Nanoparticle- aptamer bioconjugates: a new approach for targeting prostate cancer cells.” Cancer Res., 64, 7668-72; Dass, C. R. (2002). “Vehicles for oligonucleotide delivery to tumours.” J. Pharm. Pharmacol., 54, 3-27; Lysik, M. A., and Wu-Pong, S. (2003). “Innovations in oligonucleotide drug delivery.” J. Pharm. Sci., 92, 1559-73; Shoji, Y., and Nakashima, H. (2004). “Current status of delivery systems to improve target efficacy of oligonucleotides.” Curr. Pharm. Des., 10, 785-96; Allen, T. M., and Cullis, P. R. (2004). “Drug delivery systems: entering the mainstream.” Science, 303, 1818-22. The entire teachings of each reference cited in this paragraph are incorporated herein by reference. Suitable doses can vary widely depending on the therapeutic being used. A typical pharmaceutical composition for intravenous administration would be about 0.1 mg to about 10 g per subject per day. However, in other embodiments, doses from about 1 mg to about 1 g, or from about 10 mg to about 1 g can be used. Single or multiple administrations of the compositions may be administered depending on the dosage and frequency as required and Attorney Docket No.11555-011WO1 tolerated by the subject. In any event, the administration regime should provide a sufficient quantity of the composition of this invention to effectively treat the subject. Useful dosages of the additional anticancer agents, such as antimitotic agents, and immuno-nanoparticle constructs can be determined by comparing their in vitro activity and the in vivo activity in animal models. Methods for extrapolation of effective dosages in mice, and other animals, to humans are known in the art; for example, see U.S. Pat. No. 4,938,949. An amount adequate to accomplish therapeutic or prophylactic treatment is defined as a therapeutically- or prophylactically-effective dose. In both prophylactic and therapeutic regimes, agents are usually administered in several dosages until an effect has been achieved. Effective doses of the additional anticancer agents and / or immuno- nanoparticle constructs vary depending upon many different factors, including means of administration, target site, physiological state of the patient, whether the patient is human or an animal, other medications administered, and whether treatment is prophylactic or therapeutic. The skilled artisan will be able to determine appropriate dosages depending on these and other factors using standard clinical techniques. In some embodiments, the therapeutically effective amount of immunomodulatory lipid nanoparticles herein is the amount effective to promote antigen presenting cell (APC) and natural killer (NK) cell driven anti-tumor response in the subject. In some embodiments, the therapeutically effective amount of immunomodulatory lipid nanoparticles described herein is the amount effective to inhibit tumor microenvironment (TME) immunosuppression in the subject. Formulations including immuno-nanoparticle constructs for administration to a subject in need thereof described herein may be conveniently presented in unit dosage form and may be prepared by any of the methods well known in the art of pharmacy. Preferably, such methods include the step of bringing the immuno-nanoparticle constructs into association with a pharmaceutically acceptable carrier that constitutes one or more accessory ingredients. In general, the formulations are prepared by uniformly and intimately bringing the active agent into association with a liquid carrier, a finely divided solid carrier, or both, and then, if necessary, shaping the product into the desired formulations. The methods of the invention include administering to a subject, preferably a mammal, and more preferably a human, the composition of the invention in an amount effective to produce the desired effect. One skilled in the art can readily determine an effective amount of immunomodulatory lipid nanoparticles and / or additional cancer therapeutics to be Attorney Docket No.11555-011WO1 administered to a given subject, by taking into account factors such as the size and weight of the subject; the extent of disease penetration; the age, health and sex of the subject; the route of administration; and whether the administration is local or systemic. Those skilled in the art may derive appropriate dosages and schedules of administration to suit the specific circumstances and needs of the subject. For example, suitable doses of the immunomodulatory lipid nanoparticles to be administered can be estimated from the volume of cancer cells to be killed or volume of tumor to which the constructs are being administered. The methods described herein contemplate single as well as multiple administrations, given either simultaneously or over an extended period of time. A pharmaceutically acceptable composition containing the immunomodulatory lipid nanoparticles and / or additional cancer therapeutic can be administered at regular intervals, depending on the nature and extent of the cancer's effects, and on an ongoing basis. Administration at a “regular interval,” as used herein, indicates that the therapeutically effective amount is administered periodically (as distinguished from a one-time dose). In one embodiment, the pharmaceutically acceptable composition containing the immunomodulatory lipid nanoparticles and / or an additional cancer therapeutic is administered periodically, e.g., at a regular interval (e.g., bimonthly, monthly, biweekly, weekly, twice weekly, daily, twice a day or three times or more often a day). The administration interval for a single individual can be fixed, or can be varied over time, depending on the needs of the individual. For example, in times of physical illness or stress, or if disease symptoms worsen, the interval between doses can be decreased. For example, the administration of immunomodulatory lipid nanoparticles and / or the additional therapeutic agent can take place at least once on day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40, or alternatively, at least once on week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20, or any combination thereof, using single or divided doses of every 60, 48, 36, 24, 12, 8, 6, 4, or 2 hours, or any combination thereof. Administration can take place at any time of day, for example, in the morning, the afternoon or evening. For instance, the administration can take place in the morning, e.g., between 6:00 a.m. and 12:00 noon; in the afternoon, e.g., after noon and before 6:00 p.m.; or in the evening, e.g., between 6:01 p.m. and midnight. In some embodiments, the immunomodulatory lipid nanoparticles administered to a Attorney Docket No.11555-011WO1 subject can be formulated in a slow release formulation in order to sustain immune stimulation by maintaining a therapeutic concentration of the immunomodulatory lipid nanoparticles, (e.g., at the site of a tumor) while alleviating the need for frequent administrations. In some embodiments, a slow release formulation can include a polymer- based hydrogel or a dendrimer. Kits The present disclosure also pertains to kits comprising one of: (a) a composition as described herein; (b) a composition as described herein in a sterile package; or (c) a pre- filled syringe or needle comprising a composition as described herein; and instructions for administering the composition as described herein to treat a clinical condition or pathology. In a further aspect, the disclosed kits can be packaged in a daily dosing regimen (e.g., packaged on cards and / or in vials to be sequentially or periodically administered, packaged with dosing cards, packaged on blisters or blow-molded plastics, etc.). Such packaging promotes products and increases ease of use for administration by a health care profession. Such packaging can also reduce potential medical errors. The present invention also features such kits further containing instructions for use. In a further aspect, the present disclosure also provides a pharmaceutical pack or kit comprising one or more packages comprising the disclosed composition. Associated with such packages can be a notice in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals or biological products, which notice reflects approval by the agency of manufacture, use or sale for human administration. In various aspects, the disclosed kits can also comprise further therapeutic agents, compounds and / or products co-packaged, co-formulated, and / or co-delivered with other components. For example, a drug manufacturer, a drug reseller, a physician, a compounding shop, or a pharmacist can provide a kit comprising a disclosed composition and another component for delivery to a patient. It is contemplated that the disclosed kits can be used in connection with the disclosed methods of making, the disclosed methods of using or treating, and / or the disclosed compositions. From the foregoing, it will be seen that aspects herein are well adapted to attain all the ends and objects hereinabove set forth together with other advantages which are obvious and which are inherent to the structure. While specific elements and steps are discussed in connection to one another, it is understood that any element and / or steps provided herein is contemplated as being Attorney Docket No.11555-011WO1 combinable with any other elements and / or steps regardless of explicit provision of the same while still being within the scope provided herein. It will be understood that certain features and subcombinations are of utility and may be employed without reference to other features and subcombinations. This is contemplated by and is within the scope of the claims. Since many possible aspects may be made without departing from the scope thereof, it is to be understood that all matter herein set forth or shown in the accompanying drawings and detailed description is to be interpreted as illustrative and not in a limiting sense. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only, and is not intended to be limiting. The skilled artisan will recognize many variants and adaptations of the aspects described herein. These variants and adaptations are intended to be included in the teachings of this disclosure and to be encompassed by the claims herein. Now having described the aspects of the present disclosure, in general, the following Examples describe some additional aspects of the present disclosure. While aspects of the present disclosure are described in connection with the following examples and the corresponding text and figures, there is no intent to limit aspects of the present disclosure to this description. On the contrary, the intent is to cover all alternatives, modifications, and equivalents included within the spirit and scope of the present disclosure. EXAMPLES The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how the compounds, compositions, articles, devices and / or methods claimed herein are made and evaluated, and are intended to be purely exemplary of the disclosure and are not intended to limit the scope of what the inventors regard as their disclosure. Efforts have been made to ensure accuracy with respect to numbers (e.g., amounts, temperature, etc.), but some errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, temperature is in °C or is at ambient temperature, and pressure is at or near atmospheric. Example 1. Multivalent Immunomodulatory Lipid Nanoparticles as “Super- Adjuvants” for Cancer Vaccination. Cancer continues to pose a significant challenge to human health worldwide, demanding innovative strategies to combat its relentless progression. Among the emerging therapeutic approaches, cancer vaccination has garnered immense attention due to its Attorney Docket No.11555-011WO1 potential to harness the immune system to target and eliminate cancer cells. However, current cancer vaccine modalities face inherent limitations that hinder their efficacy. To address these challenges, the field of cancer vaccination is now witnessing a paradigm shift with the integration of engineered nanoparticles as a potent immunomodulatory platform. Engineered nanoparticles offer numerous advantages over conventional approaches, including enhanced antigen presentation, controlled release kinetics, and improved immune cell targeting. Their unique physicochemical properties enable precise modulation of immune responses, ultimately leading to robust and durable antitumor immunity. In this Example, an engineering approach to cancer vaccination is described utilizing a “super- adjuvant” immunomodulatory lipid nanoparticle (immuno-NP) that generates tumor- specific CD8+ T cells in the systemic blood circulation upon lymph-node directed subcutaneous delivery in the tissue. The efficacy of this vaccine is demonstrated in the B16F10 melanoma model with 80% of vaccinated mice rejecting tumor challenge. Figures 1A-1D illustrate the structure and size of dual-agonist loaded immuno-NPs conjugated to one or more tumor antigenic peptides. As shown in this example, these immunomodulatory lipid nanoparticles can function as a “super-adjuvant” to drive enhanced CD8+ T cell priming via lymph-node directed delivery in the tissue. As illustrated in Figure 1B, the dual-agonist loaded immuno-NPs can synergistically promote of Type I IFNs and other proinflammatory cytokines. These nanoparticles had an average particle size, as determined by dynamic light scattering, of from 30-40 nm. Figures 2A-2C illustrate preliminary experiments demonstrating the ability of immuno-NP-peptide formulations the drive antigen-specific CD8+ T cell responses when administered systemically. Figures 3A-3F show the ability of multivalent immune-NPs to elicit enhanced circulating tumor-specific CD8+ T cell populations as compared to single peptide formulations. Figures 4A-4E show the ability of “super-adjuvant” immuno-NPs to drain to lymph nodes from subcutaneous tissue following local administration (e.g., via subcutaneous injection). Figures 5A-5C illustrate the ability of multivalent “super-adjuvant” immune-NP- peptides to confer immunity to a subsequent B16F10 challenge. Figure 5A is a plot showing the percent of starting weight of animals during the course of the treatment protocol (day 0 = prime, day 14 = boost, and day 35 = boost) and through challenge with B16F10 (challenge at day 54) and beyond. Figure 5B is a plot showing the effect of Attorney Docket No.11555-011WO1 treatment with multivalent “super-adjuvant” immune-NP-peptides on tumor volume. Figure 5C is a plot showing the effect of treatment with multivalent “super-adjuvant” immune-NP- peptides on survival. Example 2: “Super-Adjuvant” Nanoparticles for Cancer Vaccination Summary Described herein is the ability of a “super adjuvant” nanoparticle (NP) system as a modular, customizable platform for next-generation cancer vaccination. Using nanomaterials engineering technology, we aim to harness not only the effective adjuvanticity of whole-pathogen vaccines, but also the safety of subunit vaccines. Our lipid- based platform co-encapsulates agonists of the Stimulator of Interferon Genes (STING) and Toll-like Receptor 4 (TLR4) pathways to promote synergistic production of Type I interferons and other proinflammatory cytokines in antigen-presenting dendritic cells (DCs) and macrophages. Compared to empty NPs and free agonists, dual-adjuvant NPs promoted increased antigen processing and presentation, drained efficiently to nearby lymph nodes, increased polyfunctional T and B cells, and improved tumor-free outcomes upon vaccination and subsequent challenge with multiple aggressive tumor cells. Introduction While vaccination has emerged in recent years as a powerful frontier in the development of effective cancer therapies by training adaptive immune cells to recognize and eliminate tumor cells1- adjuvanticity has remained a hurdle. Vaccines have two essential components, an antigen, which is uniquely expressed on the pathogen (or cancer cell), and an adjuvant, which activates the innate costimulatory signaling critical for priming an adaptive immune response7,8. Historically, vaccine design has transitioned from whole-pathogen vaccines to modern-day subunit vaccines to mitigate the risk of infection upon inoculation, but this shift has introduced notable trade-offs in efficacy. Chief among these limitations is that subunit vaccines largely include only single-adjuvant formulations, unlike their whole-pathogen counterparts, which include multiple innate immune agonists (or adjuvants) that together provide robust adjuvanticity7,9- vaccines fail to promote sufficient costimulatory signaling by antigen-presenting dendritic cells (DCs), these DCs, in turn, prime only suboptimal CD8+T cell responses that are neither sustained nor effective, especially in complex diseases like cancer that escape immunosurveillance a critical gap in the development of vaccine technology that urgently warrants the design of novel systems that offer tunable control to harness not only Attorney Docket No.11555-011WO1 the effective adjuvanticity of whole-pathogen vaccines, but also the safety of subunit vaccines. Materials and Methods Experimental design. Sample sizes were determined based on those reported in previous publications and no statistical method was used to predetermine sample size. The indicated sample size (N) represents biological replicates. All experiments were repeated independently 2-3 times. All samples that met appropriate experimental conditions were included in the analysis. For in vitro experiments sample allocation was performed randomly. Data collection and analysis were not performed in a blinded manner. Animal studies. All mouse experiments in this study were approved by the University of Massachusetts Chan Medical School Internal Animal Care and Use Committee (IACUC). Mice were maintained under specific pathogen-free conditions and food and water were provided ad libitum. Albino C57BL / 6 and Balb / c mice were purchased from Jackson Laboratory. Nanoparticle synthesis and characterization. Dual-adjuvant NPs were synthesized by pulsed ultrasonication. Equimolar amounts of DOPC (43.5 mol% 1,2-dioleoyl-sn- glycero-3-phophocholine, Avanti) and DSPC (43.5 mol%1,2-distearoyl-sn-glycero-3- phosphocholine, Avanti) were prepared, along with 10 mol% cholesterol and 3 mol% mPEG2000-DSPE [methoxy-poly(ethyleneglycol)-20001,2-distearoyl-sn-glycero-3- phophoethanolamine-N, Laysan Bio]. MPLA (Sigma-Aldrich) and cdGMP (Invivogen), were added as needed. For some experiments, a lipophilic fluorescent Di tracer (i.e. DiI, DiD) was also added at 0.1 mol%. Films were rehydrated in PBS and samples were ultrasonicated on ice with pulsing for a total of 5 min. NPs were then dialyzed for 1 h in 20k MWCO Slide-a-lyzer dialysis units (Thermo Fisher) against sterile PBS. For covalent peptide addition, DSPE-PEG-NH2 (Laysan Bio) was used in lieu of mPEG2000-DSPE and a sulfo-SMCC cross-linker (ThermoFisher) was used for conjugation. Dynamic light scattering (DLS) and zeta potential were used to measure NP hydrodynamic size and surface, respectively, using a Malvern Zetasizer. A commercially available cdGMP detection kit (Lucerna Technologies) was used to quantify cdGMP encapsulation. For MPLA encapsulation, a commercially available kinetic chromogenic LAL assay (Lonza) was used to quantify free MPLA and MPLA encapsulation was calculated using [((ug added) - (ug free MPLA detected)) / (ug added)] . Empty NPs prepared without addition of MPLA and cdGMP were used as a vehicle control. A commercially available Pierce Quantitative Peptide assay (Thermo Fisher) was used to quantify peptide loading and Attorney Docket No.11555-011WO1 dosing. For LC-MS, The HPLC trace spectra were collected using HPLC Agilent Technology, 1260 infinity connected to an ultrahigh performance 6130 quadrupole LC-MS, which was equipped with a reverse-phase C18 column (2.7 ^m particle size, 4.6 X 50 mm), atmospheric pressure electrospray (ESI) mass spectrometry detector, and UV-vis detector. Acetonitrile : Water (0.1% Formic Acid) were used as the mobile phases on a gradient method of 0% to 100% acetonitrile for 12 min at a flow rate of 1.0 mL / min. Tumor cell lysate preparation. Cells were trypsinized, washed, collected, and resuspended at 1 x 106cells / mL in Dulbecco’s phosphate-buffered saline (DPBS), then subjected to five freeze−thaw cycles in liquid nitrogen and a 37°C water bath. Cellular debris was removed by centrifugation at 10,000 x g for 10 min, and the supernatant was then collected as the protein lysate. Total protein concentration was measured using the bicinchoninic acid (BCA) assay with albumin as the protein standard (Pierce, ThermoFisher Scientific). In vitro immune cell activation experiments. All cells were cultured in DMEM with 10% fetal bovine serum (Genesee Scientific) and 1% penicillin / streptomycin (Genesee Scientific).1 x 106RAW 264.7 macrophages per well were cultured on a 24-well plate and treated with either free agonists or agonist-loaded NPs at indicated concentrations. At 24 hr, culture supernatant was harvested and analyzed using commercially available mIFN^ and mIFN^ ELISA kits (Invivogen). Duplicate samples were sent for third party analysis via 32- plex chemokine / cytokine discovery assay (Eve Technologies). iBMDMs derived from WT, Irf3- / -, Irf5- / -, and Irf7- / -C57BL / 6J mice were cultured at 1 x 106cells per well on a 12-well plate and treated with empty NPs, single-adjuvant NPs, or dual-adjuvant NPs. Culture supernatant was harvested at 24 hr and analyzed using commercially available mIFN^ and mIFN^ ELISA kits (Invivogen) as well as 32-plex chemokine / cytokine discovery assay (Eve Technologies). Primary DC preparation. Splenic DCs were harvested from B16-FLT3L flank tumor bearing mice. C57BL / 6 mice were inoculated s.c. on the hind flank with 1 x 106B16- FTL3L cells. On day 21 post-injection, mice were euthanized and spleens were harvested and processed into single-cell suspensions. A magnetic bead sorting kit was used to isolate CD11c+DCs (Stem Cell Technologies). In a 24-well plate, 1x106cells were cultured with NPs and harvested at 24 hr for analysis by mIFN^ and mIFN^ ELISA (Invivogen) as well as 32-plex chemokine / cytokine discovery assay (Eve Technologies). Attorney Docket No.11555-011WO1 Human DC preparation. For human DCs, PBMCs were isolated using a Ficoll density gradient and CD14+monocytes were positively selected using a StemCell Easy Human CD14 Positive Selection Kit II (StemCell #17858).1x106CD14+cells were plated in each well of a 24-well plate and incubated at 37C with 5% CO2in 1mL of RPMI Medium 1640 containing the following additives: HI FBS (GeminiBio #100-106-500), PenStrep, 10,000U / mL (100X) (Gibco # 15140-122), L-Glutamine 200mM (100X) (Gibco # 25030- 081), 2-Mercaptoethanol 55mM (1000X) (Gibco # 21985-0223), Recombinant Human GM- CSF (carrier-free) (BioLegend # 572904), Recombinant Human IL-4 (carrier-free) (BioLegend # 574006). On day 2, 1 mL of fresh media was added to the culture. On day 5, 1mL of supernatant was removed and 1mL fresh media was added to the culture. On day 7, cells were treated with the indicated formulation and samples were harvested on day 8. Non-encapsulated LPS and diABZI were used as positive controls. qRT-PCR. Total RNA was extracted from CD11c+splenocytes using the RNeasy Plus Mini Kit (Qiagen) after treatment of 1 x 106cells with NPs. Complementary DNA (cDNA) was synthesized using ABScript Neo RT Master Mix (Abclonal). Real time qPCR was performed in duplicate using Universal SYBR Green Fast qPCR (Abclonal). The comparative CT method (2−^^CT) was used to quantify fold differences between the target gene and the reference gene (GAPDH). Primer sequences are listed in Table 1. Table 1. RT-qPCR primer sequences. S S S S S S S S Attorney Docket No.11555-011WO1 S S S S S S S Drug treatments and IFNAR depletion. NPs were delivered via s.c. injection at the tail base with half of the dose on each side. For first doses (prime), mice were given 10 µg of peptide, 10 ug cdGMP and 8 ug MPLA. Peptide sequences are listed in Table 2. For subsequent doses (boost), mice were given 20 µg of peptide, 10 µg cdGMP, and 8 µg MPLA. To neutralize IFNAR signaling, mice were i.p. injected with an IFNAR-1 antibody (200 ^g; MAR15A3, BioXcell) twice per week. Table 2. Antigenic peptide sequences S S S S S S In vivo lymph node draining and activation experiments. For tail base injection site draining, mice were injected with equal subcutaneous (s.c) doses of dual-adjuvant NPs containing DiI lipophilic dye and Trp2 peptide with half of the dose on either side. At 1 hr after injection, mice were imaged using an IVIS Spectrum imaging system. A free NP standard curve was generated using serial dilutions of free NPs in a black 96 well-plate. For Attorney Docket No.11555-011WO1 lymph node accumulation, mice were euthanized at 24 hr post-prime and inguinal and axillary lymph nodes were harvested and kept hydrated in PBS for fluorescent imaging on IVIS. Both injection site draining and lymph-node accumulation studies were performed after a first dose (prime) and a third dose (post-second boost). All IVIS images were analyzed via LivingImage software (PerkinElmer). For comparison of empty vs. dual- adjuvant NP draining, mice were injected s.c. in the tail base with dual-adjuvant NPs (labeled with DiD fluorescent dye) and the right side, and empty NPs (labeled with DiI fluorescent dye) on the left side and the injection site on each side was clearly delineated. At 30 min post-injection, mice were euthanized and the entire depth of skin composing the injection site was harvested from each side separately. Skin samples were processed for flow cytometry and stained with antibodies against CD11c and F4 / 80 to assess NP uptake. Immunofluorescence. Fresh tissues were embedded in OCT, frozen, and cut into 5 ^m sections (taken from the center of the tissue). Tissue sections were placed in humidity chambers for staining. In brief, samples were washed with PBS prior to fixation with 2% PFA. PFA was removed and protein blocking solution was added. The following primary antibodies diluted in protein blocking solution were added to the tissue and incubated overnight at 4°C: CD11c (1:100, N418, Thermo Fisher), IFN^ (1:100, polyclonal, Thermo Fisher), CD80 (1:100, RM80, Thermo Fisher), CD8a (1:100, 53-6.7, Thermo Fisher), IFN^ (1:100, polyclonal, Thermo Fisher), TNF^ (1:100, polyclonal, Thermo Fisher). Fisher). Tissues were then washed with PBS and secondary Alexa Fluor 488, 594, or 647 dye- conjugated antibodies (Thermo Fisher) were added diluted 1:150 in protein blocking solution for 1 hr. Tissue sections were washed with PBS and mounting media with or without DAPI (Vectashield) was added prior to applying a glass coverslip. Z-stack images were obtained using a Nikon A1 confocal microscope and fluorescence was analyzed and quantified using Fiji / ImageJ software. Flow cytometry and intracellular cytokine staining. For tracking systemic immune responses from vaccination, mice were bled retro-orbitally once per week. Blood was centrifuged at 1,500 x g for 10 min to separate plasma. To assess circulating antibody responses, plasma was cultured with 1 x 106tumor cells per well in a 12-well plate for 30 min. Then, cells were trypsinized, washed, and stained using an IgG1 antibody (BV421, Thermo Fisher) for 30 min. Cells were washed with 100 µl of DAPI containing FACS buffer (Thermo Fisher, diluted 1:1000) and fixed with 2% PFA for 1 hr before resuspension in PBS for flow analysis. Cells from retro-orbital bleeding were plated on a 96-well plate at 100 µl per well. Red blood cells were lysed with ACK buffer (Gibco). Then, cells were Attorney Docket No.11555-011WO1 stimulated for 2 hr at 37°C in DMEM containing 2 µg of peptide per well. For ICS, a commercially available fixation / permeabilization kit containing brefeldin A (BD Biosciences) was used. Briefly, after stimulation, 1 µl of GolgiPlugTMwas added to each well and incubated for 4 hr at 37°C. Fc block diluted 1:50 in FACS buffer was added prior to staining at 4°C for 30 min using 1 µg per well of each of the following fluorescent antibodies in 50 µl FACS buffer per well: CD8a (53-6.7, FITC, Thermo Fisher), CD4 (GK1.5, APC-Cy7, BioLegend) and CD19 (eBIO1D3, PE-Cy7, BioLegend). Cells were washed with DAPI and washed 2x prior to resuspension in 100 µl of Fix / Perm solution and incubation at 4°C for 20min. Then, cells were washed 2x with 200 µl Perm / Wash buffer. For cytokine staining, antibodies against IFN^ (polyclonal, PE, Thermo Fisher) and TNF^ (polyclonal, APC, Thermo Fisher) were diluted in Perm / Wash buffer and added to samples at 0.25 µg per well and incubated at 4°C for 30 min. Cells were washed 2x with Perm / Wash buffer and fixed in 0.25% PFA overnight at 4°C. PFA was then removed and cells were resuspended in PBS for flow analysis using a BioRad ZE5 Cell Analyzer. Flow cytometry data was analyzed using FlowJo software. For B16-OVA experiments, mice were vaccinated with SIINFEKL peptide and a commercially available tetramer was used for flow (CosmoBio USA, MBL-TS-5001-1C). Tumor challenge and measurement. For flank challenge, cells were cultured in DMEM containing 10% FBS and 1% penicillin / streptomycin. Cells were trypsinized, washed with PBS, and 5 x 105cells per mouse were injected s.c. into the right hind flank. Tumor growth was monitored at least 3x per week using calipers. For i.v. rechallenge, 1x106cells were injected into the tail vein of mice that had rejected flank tumor challenge after 4 weeks. Responses were assessed via tumor volume, weight monitoring, and survival. Lung dissection was performed for quantitative assessment of metastases in i.v. rechallenge experiments Results and Discussion In this example, we use a versatile nanomaterials engineering approach to address this critical gap and report on the development and testing of a dual-adjuvant lipid-based nanoparticle (NP) system, termed “super adjuvant” NPs, that promotes powerful vaccine- specific immune responses when co-delivered with tumor antigen or lysate and directed to lymph nodes as a prophylactic approach. Effective engineering of “super adjuvant” NPs relies on several pivotal design parameters, including amenability for stable co-encapsulation and co-delivery of physically distinct but functionally synergistic innate agonists, tunability of synthesis methods to Attorney Docket No.11555-011WO1 achieve small sizes that promote rapid lymphatic draining, and facile functionalization of surfaces to promote inert and water-soluble properties that prevent harmful aggregation in tissue14-18. Efforts have been made in recent years to develop NP-based adjuvants, including polymer-based19and lipid-based18systems, which have been designed to encapsulate individual adjuvants such as cytosine-guanosine motifs (CpG)20, polyinosinic- polycytidylic acid [poly(I:C)])21, Stimulator of Interferon Genes (STING) agonists22-24as well as combinations of agonists such as CpG / poly(I:C)25, Resiquimod (R848) / lipopolysaccharide (LPS)26, CpG / mannose27, monophosphoryl lipid A (MPLA) / CpG28, and others29,30. Despite recent advances in the identification of peptide neoantigens, many cancer vaccines that have undergone clinical trials have exhibited little to no benefit factors have played a role in the limited translational efficacy of vaccine formulations, which have utilized NP-based adjuvants, including insufficient immunogenicity of antigens, limited lymph node accumulation, and insufficient adjuvanticity of the overall formulation33,34. Recent clinical trials have utilized a cocktail of peptide neoantigens along with free poly(I:C) stabilized by poly-L-lysine double-stranded RNA (poly ICLC) as an adjuvant; however, these trials have still yielded only mild CD8+T cell responses against a fraction of screened antigens and have shown limited therapeutic efficacy35. Thus, there is a critical clinical need for next-generation engineering approaches that optimize cancer vaccines to drive sufficient tumor-specific immunity. We focus io this example specifically on the attributes of lipid-based nanomaterials, which enable co-encapsulation of hydrophilic and hydrophobic agonists on the same NP, synthesis within a small ~30-60-nm size window (polydispersity index, PDI, ~0.2) for rapid draining to lymph nodes and ready uptake by target DCs, and “stealth” poly(ethylene glycol) (PEG) surface functionalization for physiological solubility (Figures 6A-6B, Figures 10A-10B). We use a neutral lipid matrix to co-encapsulate hydrophilic cyclic-di guanosine monophosphate (cdGMP), an agonist of the Stimulator of Interferon Genes (STING) pathway36, and hydrophobic monophosphoryl lipid A (MPLA), an agonist of the Toll-like Receptor 4 (TLR4) pathway37together on the same NP for co-delivery to the same target DC (Figures 6A-6B). Previously delivered as a systemic formulation and directed to tumors, we demonstrated that dual-adjuvant NPs promoted IFN^-mediated expansion of tumor antigen-presenting cells (APCs), such as dendritic cells (DCs), macrophages, and natural killer (NK) cells, and harnessed CD8+T cell-mediated anti-tumor control for clearance38- This synergistic cytokine production has been attributed to downstream amplification of shared pathways (IRF3, NF-^B)40,41, but has yet to be demonstrated mechanistically. Attorney Docket No.11555-011WO1 In this example, we shift our perspective and report on the utility of dual-adjuvant NPs for lymph node-directed vaccination. Since identification of immunogenic epitopes has been a bottleneck for cancer vaccination42, we engineered this system to be delivered alongside antigenic peptides or tumor cell lysates, allowing for a modular, customizable, and adaptable strategy without the need for whole-genome sequencing or complex bioinformatics screening, as is currently performed in ongoing trials10. Very recently, polymeric materials have been reported to be effective41, but here we take advantage of lipid-based materials, which are highly biocompatible and biodegradable as well as scalable and cost-effective43. demonstrate the efficacy, tunability, and versatility of our NPs as “super adjuvants” across primary DCs and macrophage cell lines and show that synergistic cytokine production depends on several transcriptional regulatory factors that are shared between STING and TLR4 pathways. We show that NPs drain efficiently to lymph nodes and characterize the circulating adaptive immune responses generated using antigenic peptides or tumor lysate. Finally, we test this system as a platform treatment across multiple aggressive tumor models, including melanoma, pancreatic ductal adenocarcinoma, and triple-negative breast cancer and report the significantly elevated rate of tumor rejection across all tumor models. Tailored engineering to optimize cytokine synergy and antigen presentation We first sought to optimize the synergy promoted by dual activation of STING and TLR4 by “super-adjuvant” NPs with in vitro experiments using immortalized macrophages and primary DCs and evaluate its impact on downstream functions related to antigen processing and presentation that are pivotal in vaccination. In initial studies designed to ask if an optimal ratio of STING / TLR4 agonists existed within defined boundary conditions of synthesis feasibility, we synthesized a range of 9 dual-adjuvant NP formulations and promotion of Type I IFNs and other proinflammatory cytokines by RAW 264.7 macrophages, compared to single-adjuvant NPs, empty NPs, and untreated controls by ELISA and multiplex cytokine analysis (Figure 6C, Figures 10C-10D). Analysis of cdGMP and MPLA loading efficiency after 1 h, 2 h, or 4 h of dialysis indicated some leakage of cdGMP, but highly stable encapsulation of MPLA, as is expected by their distinct physical attributes (Figures 10C, 10F). We confirmed similar loading efficiency using LC-MS detection for cdGMP, with no significant difference in loading capacity of the dual agonist formulation compared to cdGMP only (Figures 10D-10E). Notably, while parallel experiments using macrophages treated with free agonist combinations (without the Attorney Docket No.11555-011WO1 nanocarrier) suggested that the STING agonist was primarily responsible for controlling the magnitude of the cytokine response (Figure 11A), our results from NP-treated macrophage studies demonstrated that both agonists were important in the synergistic response. Specifically, when agonists were co-encapsulated in NPs, our results demonstrated that a ~1-2.5 mole ratio of cdGMP / MPLA and increasing absolute concentrations of each agonist promoted peak synergy for Type I IFNs and elevated production of other prominent cytokines, including TNF^, IL-6, RANTES, G-CSF, CCL2, CCL3, CCL4, CXCL5, and others (Figure 6C, Figure 11B), suggesting that the unpacking process of encapsulated agonists from a NP upon uptake might lead to altered response kinetics. Based on these results, we synthesized “super-adjuvant” NPs carrying a 2.5 mole ratio of cdGMP / MPLA and 45 µM and 20 µM of cdGMP and MPLA, respectively, and asked whether synergy occurred in primary splenic CD11c+DCs (Figure 6D). Even in these cells, dual-adjuvant NPs promoted significant >4-fold increased production of both Type I IFNs, IFN^ and IFN^, compared to single-adjuvant or empty NP controls. Further, multiplex cytokine analysis demonstrated that synergistic production of other key proinflammatory cytokines was also present (Figure 11C). Collectively, this group of cytokines are involved in innate immune activation, immune trafficking, and CD8+T cell recruitment. For all following in vitro experiments, we used dual-adjuvant NPs synthesized with a 2.5 cdGMP / MPLA mole ratio carrying 45 µM and 20 µM of each respective agonist. Given the well-established role of Interferon Regulatory Factors (IRFs) in the transcription of Type I IFNs, we next sought to assess whether the synergistic response between STING and TLR4 pathway activation was dependent on the IRF3, IRF5, or IRF744-46. We treated Irf3, Irf5, Irf7 knock-out (KO), or wildtype (WT) immortalized bone marrow-derived macrophages (iBMDMs) with dual-adjuvant NPs and measured production of Type I IFNs and other proinflammatory cytokines by ELISA and multiplex cytokine analysis and compared these levels to cells treated with single-adjuvant and empty NPs (Figure 6E, Figures 11D-11G). IRF3, IRF5, and IRF7 were all found to play significant roles in promotion of both Type IFNs when both STING and TLR4 pathways were activated, even though the absence of IRF7 still enabled the production of lower but notable levels of IFN^ (Figure 6E). We confirmed ability of dual-adjuvant NPs to promote significant production of IFN^ in human DCs from three independent patient donors (Figure 6F), broadening the relevance and translational capacity of this work. Since upregulated Type I IFN expression has been shown to increase antigen processing and presentation, we asked whether dual STING / TLR4 activation might Attorney Docket No.11555-011WO1 augment these functions in splenic CD11c+DCs by treating DCs with dual-adjuvant NPs and measuring expression of B2m, Erap1, H2d1, H2k1, Tap1, and Tap2 by qRT-PCR (Figure 6G, Table 1). We found all of these genes expressed at significantly higher levels compared to single-agonist NP, empty NP, and untreated controls, and noted that expression of Tap1 and Tap2 transporters was synergistically elevated (Figure 6G). These results strongly highlighted the enhanced adjuvanticity of our dual-adjuvant NPs, underscoring their utility as “super adjuvants”. Efficient draining to lymph nodes and activation of DCs Following our in vitro studies, we next sought to establish the lymph node draining capability of “super adjuvant” NPs from the site of vaccination, which is critical in mediating their efficacy in vivo. We administered fluorescent NPs carrying 13.6 nM cdGMP and 4.5 nM MPLA to mice via subcutaneous (s.c.) injection at the tail base. Empty NPs were used as controls. To evaluate whether dual-adjuvant NPs were selectively taken up more efficiently by APCs in the skin, we euthanized a subset of mice 30 min post-injection and processed the skin tissue at the tail base for flow cytometry (Figure 12A). While NPs were found in a substantial number of cells (~50% of viable cells, ~70% of F4 / 80+macrophages, and ~73% of CD11c+DCs), there were no differences in uptake at this short- term timepoint between dual-adjuvant and empty NPs. Further, there were no significant differences in draining of NPs from the injection site at 1 hr in mice that received only a prime or both a prime (day 0) and subsequent boost (day 14), with 36% of dual-adjuvant NP dose draining away after a prime and 55% draining away after a boost. (Figure 12B). Here, we followed a standard established prime-boost schedule for murine models47. Despite no notable differences in short-term uptake by APCs at the injection site, we next assessed whether dual-adjuvant NPs could accumulate in lymph nodes more efficiently compared to empty NPs. Dual-adjuvant or empty NPs were administered at the tail base of mice for either a prime or a prime (day 0) followed by a boost (day 14) and, following euthanization 24 hr later, nearest draining inguinal and axillary lymph nodes were harvested and analyzed ex vivo by Spectrum imaging for NP fluorescence (Figure 7A). While dual- adjuvant NPs drained at elevated levels compared to empty NP controls to nearest draining inguinal lymph nodes after the initial prime, these differences were most striking and significant after the boost with >3-fold increased signal compared to empty NPs (Figure 7A). We euthanized a subset of mice that received only the initial prime 24 hr after injection and stained inguinal lymph node sections for CD11c+DCs, CD8+T cells, and their Attorney Docket No.11555-011WO1 activation markers (Figures 7B-7C). Confocal microscopy analysis demonstrated a significant increase in CD11c+DCs and their expression of the activation marker CD80, as well as elevated levels of IFN^ in lymph nodes of mice that received dual-adjuvant NPs (Figure 7C). Dual-adjuvant NPs were also present to a notable extent in lymph node sections that also stained positive for CD8+T cells (Figures 12C-12D). Although a significant increase in lymph node accumulation following dual-adjuvant NPs compared to empty NPs was observed via whole-organ imaging (Figure 7A), this difference was not observed in confocal analysis (Figure 7C), likely due to the regions chosen for imaging being only a portion of the overall lymph node. Biodistribution analysis at 48 h post- injection showed no significant differences in empty versus dual-adjuvant NP accumulation in the tail base, blood plasma, liver, kidneys, lungs and spleen (Figure 12E). In particular, there was a significant increase in lymph node accumulation in the immune-NP treated mice (Figure 12F). Taken together, these findings suggested that the physical attributes of the NPs (e.g., hydrodynamic size, surface charge) do not impede their lymphatic trafficking, which is an advantage of our tunable lipid-based system. The elevated deposition of dual- adjuvant NPs in lymph nodes after 24 hr suggests that dual STING / TLR4 activation may promote more efficient ferrying by DCs over time. To assess the therapeutic window of our “super adjuvant” vaccine, mice were treated with varying doses of NPs (half, full, and twice the total dose). Flow cytometry analysis showed that the full-dose of dual-adjuvant NPs induced significant circulating polyfunctional CD8+T cells, while the half- and double-dose groups showed strikingly weaker responses (Figure 12G). These findings suggest that there may be a form of negative feedback or dampening of innate sensing machinery upon administration of particularly high doses of this system. Analysis of blood plasma revealed significant increase in ALT levels following a half dose of the prime and a double dose of the first boost and mouse weight loss was slightly increased in the double-dose group, indicating higher levels of systemic toxicity that did not correlate with better T cell responses (Figures 12H-12I). Efficacy as a platform treatment with multivalent peptides Having determined that “super adjuvant” NPs drain effectively to lymph nodes with evidence of their uptake by and activation of lymph-resident DCs, we sought to evaluate their adjuvanticity in vivo as a platform treatment that is amenable to co-delivery with multiple peptides. Using the B16F10 mouse model of melanoma, we first elected to co- deliver dual-adjuvant NPs with tumor-associated antigenic peptides, Trp1, Trp2, or gp100 that have been shown to be recognized by CD8+T cells (Table 2)48-50. After confirming that Attorney Docket No.11555-011WO1 NPs remained unaltered upon addition of peptides (Figures 13A-13B), we vaccinated mice with NPs and single peptides s.c. at the tail base using a standard prime-boost regimen to assess their individual immunogenicity (Figure 8A). Flow cytometry analysis demonstrated that levels of blood CD8+T cells were highest 1 week post-second boost and notably so for Trp2 peptides and NPs compared to Trp2 peptides and free agonists, with strong statistical significance for polyfunctional CD8+T cells that were producing both IFN^ and TNF^ as measured by intracellular cytokine staining (Figures 13C-13E). Notably, none of the single peptide-NP formulations provided sufficient immunity for tumor rejection and there was no significant survival benefit observed (Figure 13F). Additionally, we assessed the extent to which chemically conjugating antigenic peptides to the surface of our NPs would affect the observed responses. For this, Trp2 peptides with cysteine residues at the N-terminus were used (either with or without a 6-glycine spacer). There was no significant increase in overall populations of circulating CD8+T cells or in the percent of polyfunctional CD8+T cells compared to non-conjugated formulations following ex vivo stimulation (Figures 13C-13F). Thus, we concluded that this conjugation step was not necessary to drive antigen specific responses and opted to simplify synthesis by using non-conjugated formulations in subsequent experiments (all peptide sequences are listed in Table 2). Upon local challenge with B16F10 tumor cells by orthotopic s.c. injection 3 weeks post-second boost, however, there was no improvement of long-term tumor-free survival across any group and all groups eventually succumbed to tumor advancement (Figure 13F). Notably, a small 20% cohort of mice treated with NPs conjugated to Trp2 (with and without the spacer) rejected tumors (Figures 13F, 13J). Finally, to assess any systemic toxicity from our dual-adjuvant NP, blood plasma was analyzed for liver enzymes alanine transaminase (ALT) and aspartate transaminase (AST) 1 week after boost injection. No significant increases in ALT or AST levels were observed (Figures 13G-13H). Mouse weight was monitored and revealed transient weight loss following injections that was regained rapidly over days (Figure 13I). We also assessed the ultility of our super-adjuvant to drive tumor specific T-cell responses in an OVA expressing B16F10 model. Here, mice were vaccinated with the SIINFEKL peptide on the same prime-boost schedule as previous experiments. Tetramer staining for the SIINFEKL-specific TCR demonstrated significantly increased populations of antigen specific CD8+T cells in the systemic circulation at 1-week post vaccination in the super adjuvant NP vaccinated group compared to single agonist NP and naïve treated mice (Figures 13K-13L). At 21 days following local tumor challenge, 80% (4 / 5) of super Attorney Docket No.11555-011WO1 adjuvant vaccinated mice were tumor free, while 0% (0 / 5) mice vaccinated with single agonist NP formulations were tumor free (Figure 13M). In single-peptide vaccination studies, since Trp1- and Trp2-specific CD8+T cell responses were sizeable compared to gp100-specific responses, we elected to formulate our multivalent compositions with Trp1 and Trp2 peptides and dual-adjuvant NPs. In these studies, mice received equivalent doses of each peptide and an initial prime (day 0), first boost (day 14), and second boost (day 28), as in our previous experiments (Figure 8A). Interestingly, vaccination with multivalent peptides and dual-adjuvant NPs generated significant populations of polyfunctional CD8+T cells compared to peptides administered with single-agonist NPs or free agonists alone (>4-fold increase) in flow cytometry analysis with intracellular cytokine staining when blood T cells were stimulated ex vivo with both peptides (Figure 8B, Figures 14C, 14F). Notably, when we compared these responses to ex vivo stimulation responses with single peptides, we found that Trp2 was primarily responsible for these polyfunctional CD8+T cells (Figures 14A-14B). Similar findings, where specific antigens have proven to be responsible for the majority of immunogenicity, have been observed in other multivalent therapies, including cancer vaccines51,52and CAR- T cells53. Two weeks after the second boost, mice were challenged locally by orthotopic s.c. injection of B16F10 tumor cells. Strikingly, 48 days post-challenge, 100% of mice vaccinated with multivalent peptides and dual-adjuvant NPs survived, while none of the mice that received peptides and free agonists or naive mice survived beyond 27 days (Figures 8C-8D, Figure 14E). There was a significant reduction in tumor volume at 27 days post-challenge in single-agonist NP-vaccinated mice compared to mice vaccinated with free peptides and agonists, but these mice failed to control tumor growth long-term and did not survive past 35 days post-challenge (Figures 8C-8D). Four weeks post challenge, all remaining tumor-free mice that received multivalent peptides and dual-adjuvant NPs (8 / 10 or 80%) were rechallenged systemically via intravenous (i.v.) injection of B16F10 cells in the tail vein. Three weeks following rechallenge, all naive mice appeared to deteriorate by weight and behavior and we euthanized this whole cohort along with a subset of mice that were vaccinated with multivalent peptides and NPs that still appeared healthy for comparison. None of the vaccinated mice exhibited any degree of lung metastasis upon inspection of lungs and liver, while all naive mice had distinct metastatic lung nodules (Figure 8E, Figure 14G). Weight loss throughout treatment was minimal and transient (Figure 14D). Attorney Docket No.11555-011WO1 Vaccination with tumor lysate for broad immune responses Given these results and the challenges associated with identifying accurate tumor- associated antigenic peptides, we finally sought to test the efficacy of our “super adjuvant” NPs in a vaccination setting where tumor antigens and neoantigens may not be clinically available. Here, to recapitulate whole-pathogen vaccination strategies, we used tumor cell lysate54,55in lieu of antigenic peptides and tested our NP system in multiple aggressive tumor models: B16F10 melanoma, Panc02 pancreatic ductal adenocarcinoma, and 4T1 triple-negative breast cancer. We hypothesized that co-delivering cell lysate with NPs would drive a broad anti-tumor immune response that would not only include CD8+T cells, but also CD4+T cells and B cells. We primed (day 0) mice with B16F10, Panc02, or 4T1 lysate and “super adjuvant” NPs, and, as previously, administered a first boost (day 14) and second boost (day 35) (Figure 9A). Flow cytometry analysis with intracellular cytokine staining of peripheral blood mononuclear cells (PBMCs) for IFN^ and TNF^ demonstrated significant populations of polyfunctional CD8+(Figure 9B, Figures 15A, 15J) and CD4+T cells (Figure 9B, Figure 15B, 15J) 1 week post-second boost, as well as polyfunctional CD19+B cells and plasma IgG antibodies 1 week post-first boost (Figure 9C, Figures 15C-15D, 15J) in mice that received the lysate and NPs compared to naive controls. Three weeks following the second boost, mice were challenged locally by s.c. injection of tumor cells and we observed remarkable tumor rejection and long-term impact on survival in mice that received lysate and NPs compared to controls: for B16F10 mice, 69% (9 / 13) of NP-vaccinated mice rejected tumors; for Panc02 mice, 88% (7 / 8) of NP-vaccinated mice rejected tumors; and for 4T1 mice, 75% (6 / 8) of NP-vaccinated mice rejected tumors (Figures 9F-9G, Figures 15F-15H). In comparison, none of the naive mice for any tumor model rejected the challenge. All remaining mice that received the NP vaccine received a systemic rechallenge by i.v. injection of tumor cells 3 weeks after the local challenge and 100% of the mice remained tumor-free across all 3 models, while none of the naive mice displayed any anti- tumor control (Figure 9G, Figure 15I). To assess the role of Type I IFNs in our therapy, we enrolled an additional group of mice that received bi-weekly doses of anti-IFNAR for blockade throughout the entire B16 lysate vaccination regimen. In this group, polyfunctional CD4+T cell responses were fully ablated and CD8+T cell responses declined (Figure 9D). Despite detectable populations of functional CD8+T cells, following local challenge, none of the IFNAR-blocked mice rejected the tumor challenge (Figure 9E), Attorney Docket No.11555-011WO1 strongly underscoring the central role of Type I IFNs for efficacy of our dual STING / TLR4 NP system. Conclusion In summary, this example presents compelling evidence for the utility of NP-based “super adjuvants”, as demonstrated both in vitro and in vivo. Our studies demonstrating efficacy with antigenic peptides or tumor lysate highlights the advantages of biocompatible lipid-based systems and makes the case of a modular platform approach for next-generation cancer vaccination. Notes and References 1 Kaczmarek, M. et al. Cancer Vaccine Therapeutics: Limitations and Effectiveness-A Literature Review. Cells 12 (2023). 2 Lin, M. J. et al. Cancer vaccines: the next immunotherapy frontier. Nat Cancer 3, 911-926 (2022). 3 Liu, J. et al. Cancer vaccines as promising immuno-therapeutics: platforms and current progress. J Hematol Oncol 15, 28 (2022). 4 Liu, H. et al. Structure-based programming of lymph-node targeting in molecular vaccines. Nature 507, 519-522 (2014). 5 Wang, Y. & Wang, H. Lymph node targeting for immunotherapy. Immunooncol Technol 20, 100395 (2023). 6 Ding, Y., Li, Z., Jaklenec, A. & Hu, Q. Vaccine delivery systems toward lymph nodes. Adv Drug Deliv Rev 179, 113914 (2021). 7 Pollard, A. J. & Bijker, E. M. A guide to vaccinology: from basic principles to new developments. Nat Rev Immunol 21, 83-100 (2021). 8 Zhao, T. et al. Vaccine adjuvants: mechanisms and platforms. Signal Transduct Target Ther 8, 283 (2023). 9 Karch, C. P. & Burkhard, P. Vaccine technologies: From whole organisms to rationally designed protein assemblies. Biochem Pharmacol 120, 1-14 (2016). 10 Biswas, N., Chakrabarti, S., Padul, V., Jones, L. D. & Ashili, S. Designing neoantigen cancer vaccines, trials, and outcomes. Front Immunol 14, 1105420 (2023). 11 Janes, M. E., Gottlieb, A. P., Park, K. S., Zhao, Z. & Mitragotri, S. Cancer vaccines in the clinic. Bioeng Transl Med 9, e10588 (2024). 12 Paston, S. J., Brentville, V. A., Symonds, P. & Durrant, L. G. Cancer Vaccines, Adjuvants, and Delivery Systems. Front Immunol 12, 627932 (2021). Attorney Docket No.11555-011WO1 13 Hanahan, D. Hallmarks of Cancer: New Dimensions. Cancer Discov 12, 31-46 (2022). 14 Li, Y. et al. Targeting lymph node delivery with nanovaccines for cancer immunotherapy: recent advances and future directions. J Nanobiotechnology 21, 212 (2023). 15 Chen, J. et al. Lipid nanoparticle-mediated lymph node-targeting delivery of mRNA cancer vaccine elicits robust CD8(+) T cell response. Proc Natl Acad Sci U S A 119, e2207841119 (2022). 16 He, R., Zang, J., Zhao, Y., Dong, H. & Li, Y. Nanotechnology-Based Approaches to Promote Lymph Node Targeted Delivery of Cancer Vaccines. ACS Biomater Sci Eng 8, 406-423 (2022). 17 Kane, G. I., Lusi, C. F., Brassil, M. L. & Atukorale, P. U. Engineering approaches for innate immune-mediated tumor microenvironment remodeling. Immunooncol Technol 21, 100406 (2024). 18 Chatzikleanthous, D., O'Hagan, D. T. & Adamo, R. Lipid-Based Nanoparticles for Delivery of Vaccine Adjuvants and Antigens: Toward Multicomponent Vaccines. Mol Pharm 18, 2867-2888 (2021). 19 Grego, E. A. et al. Polymeric Nanoparticle-Based Vaccine Adjuvants and Delivery Vehicles. Curr Top Microbiol Immunol 433, 29-76 (2021). 20 Lanza, J. S. et al. A TLR9-adjuvanted vaccine formulated into dissolvable microneedle patches or cationic liposomes protects against leishmaniasis after skin or subcutaneous immunization. Int J Pharm 586, 119390 (2020). 21 Zaks, K. et al. Efficient immunization and cross-priming by vaccine adjuvants containing TLR3 or TLR9 agonists complexed to cationic liposomes. J Immunol 176, 7335- 7345 (2006). 22 Zhou, Q., Zhou, Y., Li, T. & Ge, Z. Nanoparticle-Mediated STING Agonist Delivery for Enhanced Cancer Immunotherapy. Macromol Biosci 21, e2100133 (2021). 23 Nakamura, T. et al. STING agonist loaded lipid nanoparticles overcome anti-PD-1 resistance in melanoma lung metastasis via NK cell activation. J Immunother Cancer 9 (2021). 24 Garland, K. M., Sheehy, T. L. & Wilson, J. T. Chemical and Biomolecular Strategies for STING Pathway Activation in Cancer Immunotherapy. Chem Rev 122, 5977- 6039 (2022). Attorney Docket No.11555-011WO1 25 Bayyurt, B. et al. Encapsulation of two different TLR ligands into liposomes confer protective immunity and prevent tumor development. J Control Release 247, 134-144 (2017). 26 Rueda, F. et al. Effect of TLR ligands co-encapsulated with multiepitopic antigen in nanoliposomes targeted to human DCs via Fc receptor for cancer vaccines. Immunobiology 222, 989-997 (2017). 27 Lai, C. et al. The enhanced antitumor-specific immune response with mannose- and CpG-ODN-coated liposomes delivering TRP2 peptide. Theranostics 8, 1723-1739 (2018). 28 Pradhan, P. et al. TRAF6-IRF5 kinetics, TRIF, and biophysical factors drive synergistic innate responses to particle-mediated MPLA-CpG co-presentation. Sci Adv 7 (2021). 29 Sun, Z. et al. The quest for nanoparticle-powered vaccines in cancer immunotherapy. J Nanobiotechnology 22, 61 (2024). 30 Liu, J., Miao, L., Sui, J., Hao, Y. & Huang, G. Nanoparticle cancer vaccines: Design considerations and recent advances. Asian J Pharm Sci 15, 576-590 (2020). 31 Niemi, J. V. L., Sokolov, A. V. & Schioth, H. B. Neoantigen Vaccines; Clinical Trials, Classes, Indications, Adjuvants and Combinatorial Treatments. Cancers (Basel) 14 (2022). 32 Blass, E. & Ott, P. A. Advances in the development of personalized neoantigen- based therapeutic cancer vaccines. Nat Rev Clin Oncol 18, 215-229 (2021). 33 Bowen, W. S., Svrivastava, A. K., Batra, L., Barsoumian, H. & Shirwan, H. Current challenges for cancer vaccine adjuvant development. Expert Rev Vaccines 17, 207-215 (2018). 34 Donninger, H., Li, C., Eaton, J. W. & Yaddanapudi, K. Cancer Vaccines: Promising Therapeutics or an Unattainable Dream. Vaccines (Basel) 9 (2021). 35 Keskin, D. B. et al. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature 565, 234-239 (2019). 36 Jiang, M. et al. cGAS-STING, an important pathway in cancer immunotherapy. J Hematol Oncol 13, 81 (2020). 37 Romero, C. D. et al. The Toll-like receptor 4 agonist monophosphoryl lipid a augments innate host resistance to systemic bacterial infection. Infect Immun 79, 3576-3587 (2011). 38 Lorkowski, M. E. et al. Immunostimulatory nanoparticle incorporating two immune agonists for the treatment of pancreatic tumors. J Control Release 330, 1095-1105 (2021). Attorney Docket No.11555-011WO1 39 Atukorale, P. U. et al. Nanoparticle Encapsulation of Synergistic Immune Agonists Enables Systemic Codelivery to Tumor Sites and IFNbeta-Driven Antitumor Immunity. Cancer Res 79, 5394-5406 (2019). 40 Atukorale, P. U. et al. Dual agonist immunostimulatory nanoparticles combine with PD1 blockade for curative neoadjuvant immunotherapy of aggressive cancers. Nanoscale 14, 1144-1159 (2022). 41 Baljon, J. J. et al. A Cancer Nanovaccine for Co-Delivery of Peptide Neoantigens and Optimized Combinations of STING and TLR4 Agonists. ACS Nano 18, 6845-6862 (2024). 42 Rui, R., Zhou, L. & He, S. Cancer immunotherapies: advances and bottlenecks. Front Immunol 14, 1212476 (2023). 43 Shepherd, S. J. et al. Throughput-scalable manufacturing of SARS-CoV-2 mRNA lipid nanoparticle vaccines. Proc Natl Acad Sci U S A 120, e2303567120 (2023). 44 Khoyratty, T. E. & Udalova, I. A. Diverse mechanisms of IRF5 action in inflammatory responses. Int J Biochem Cell Biol 99, 38-42 (2018). 45 Fitzgerald, K. A. et al. LPS-TLR4 signaling to IRF-3 / 7 and NF-kappaB involves the toll adapters TRAM and TRIF. J Exp Med 198, 1043-1055 (2003). 46 Kawai, T. & Akira, S. Toll-like receptor downstream signaling. Arthritis Res Ther 7, 12-19 (2005). 47 Palgen, J. L. et al. Optimize Prime / Boost Vaccine Strategies: Trained Immunity as a New Player in the Game. Front Immunol 12, 612747 (2021). 48 Mansour, M. et al. Therapy of established B16-F10 melanoma tumors by a single vaccination of CTL / T helper peptides in VacciMax. J Transl Med 5, 20 (2007). 49 Moynihan, K. D. et al. Eradication of large established tumors in mice by combination immunotherapy that engages innate and adaptive immune responses. Nat Med 22, 1402-1410 (2016). 50 Yazdani, M. et al. Liposomal gp100 vaccine combined with CpG ODN sensitizes established B16F10 melanoma tumors to anti PD-1 therapy. Iran J Basic Med Sci 23, 1065- 1077 (2020). 51 Reynolds, S. R. et al. HLA-independent heterogeneity of CD8+ T cell responses to MAGE-3, Melan-A / MART-1, gp100, tyrosinase, MC1R, and TRP-2 in vaccine-treated melanoma patients. J Immunol 161, 6970-6976 (1998). Attorney Docket No.11555-011WO1 52 Liu, C. J. et al. Treatment of an aggressive orthotopic murine glioblastoma model with combination checkpoint blockade and a multivalent neoantigen vaccine. Neuro Oncol 22, 1276-1288 (2020). 53 Spiegel, J. Y. et al. CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial. Nat Med 27, 1419- 1431 (2021). 54 Callmann, C. E. et al. Tumor cell lysate-loaded immunostimulatory spherical nucleic acids as therapeutics for triple-negative breast cancer. Proc Natl Acad Sci U S A 117, 17543-17550 (2020). 55 Won, J. E. et al. Enhanced Antitumor Immunity Using a Tumor Cell Lysate- Encapsulated CO(2)-Generating Liposomal Carrier System and Photothermal Irradiation. ACS Appl Bio Mater 2, 2481-2489 (2019). Example 3. Immunostimulatory Lipid Nanoparticles Drive Immune Responses to Dormant Metastases in a Triple-Negative Breast Cancer Model. Metastasis is responsible for an overwhelming 90% of cancer mortality, and within breast cancer alone, dormant metastasis contributes to over 60% of deaths. Since dormant metastases are non-dividing, dormant tumor cells are not effectively cleared by standard-of- care chemotherapy and can remain quiescent for years following initial treatment only to undergo poorly understood programmatic shifts to aggressive chemo-resistant metastases. Therefore, there is a critical clinical need to develop “smart” therapeutics that can target and reach early dormant metastatic niches to drive tumor clearance using mechanisms that bypass chemo-resistance entirely, such as immunotherapy. In this example, we describe an innate immunomodulatory lipid-based nanoparticle system that can be safely delivered in the systemic blood circulation to co-deliver agonists of the Stimulator of Interferon Genes (STING) and Toll-like Receptor 4 (TLR4) pathways. Co-activation of STING and TLR4 pathways promotes a powerful synergistic production of proinflammatory Type I interferons by target cells. In this example, we exploited the modular nature of these nanoparticles and attach various targeting peptides on their surface to direct them to specific cell subsets in the dormant tumor microenvironment in mice bearing D2.OR metastases. Specifically, we investigated the immunotherapeutic efficacy in nanoparticles targeted to tumor endothelial cells, tumor matrix for targeting antigen-presenting cells, and tumor cells themselves. We Attorney Docket No.11555-011WO1 correlated targeting efficiency with Type I interferon expression, T cell activation, tumor clearance, and immunological memory against genetically identical and isogenic tumors. Figures 16A-16E show the rationale used for targeting the nanoparticle formulations described herein. Figure 17 illustrates the characterization of evaluated nanoparticle treatments. Figures 18A-18C show the evaluation of the impact of a single dose of individual targeted nanoparticle formulations. Figures 19A-19B show the evaluation of the impact of increased dosage of targeted nanoparticle formulations. Simultaneous delivery of STING and TLR4 agonists via nanoparticles outperformed the systemic delivery of free agonists. The delivery of these immune agonists in a targeted fashion minimizeed tumoral growth in comparison to untreated groups. These results suggest that each type of targeted nanoparticle offers distinct functionalities and that an optimal therapy can be designed with a rationally selected combination of targeted nanoparticles. Lipid-based nanoparticle (NP) systems that co-encapsulate agonists of the STING and TLR4 pathways together on the same NP can promote the synergistic production of Type I interferons (IFNs). Type I IFNs are central in the cytokine remodeling of the tumor microenvironment (TME) from immunosuppressive or cold to proinflammatory or hot. In this example, we evaluated multi-targeted STING / TLR4 NPs for the treatment of dormant and aggressive metastasis. Our studies used two isogenic models of metastasis, the D2.HAN models of lung cancer, including the D2.OR (dormant) and D2.A1 (aggressive) models, and the 4T models of triple-negative breast cancer, including the 4T07 (dormant) and 4T1 (aggressive) models. NPs are systemically delivered in the blood circulation of mice bearing metastatic tumors that most predominantly manifest in the lungs. The multi-targeted NP system aims to direct NPs to: (a) the tumor extracellular matrix (ECM) via a peptide that binds to unique fibrin-fibrinogen motifs, to target sentinel antigen-presenting cells (APCs), such as dendritic cells (DCs) and macrophages, as well as stromal cells or fibroblasts, (b) endothelial cells via peptides for P-selectin and / or ^^^3 integrins, and (c) tumor cells via peptides that bind to EGFR and / or ^^^3 integrins. Peptides are covalently conjugated to NPs via crosslinking to terminal amine moieties on PEG chains on the surface of NPs. Peptides are functionalized with a cysteine amino acid on the N- terminus for crosslinking. Due to the tunable platform nature of this strategy, we will continue to explore the utility of these three classes of cell types within the TME, and expect our future treatments to include other peptide targets for these cells. Attorney Docket No.11555-011WO1 Key findings that are related to the mechanism of efficacy of our NP system include: (a) Results suggest that dormant metastasis may be more readily treatable as tumor cells are quiescent compared to aggressive tumor cells that are highly proliferative. Effective treatment of dormant metastasis following targeted NP therapy can lead to immunological protection of isogenic aggressive cancers, highlighting the significant utility of our in situ TME remodeling system that can confer protection against recurrence of multiple related tumor types without requiring prior knowledge of specific tumor antigens. (b) Even key non-immune cell types within the TME can be exploited for immunotherapy, including cells that highly express STING and TLR sensing machinery, such as fibroblasts and endothelial cells. (c)Unexpectedly, either by targeting them directly and / or targeting other cells in the TME, we have found that tumor cells can also be exploited as a pivotal source of antigens for immune recognition and subsequent clearance. This finding is unexpected as tumor cells are known to downregulate their innate sensing pathways. Specifically, dormant tumor cells may be coaxed out of their quiescent state by promoting their Type I IFN production, effectively unmasking them, and enabling their immune recognition. Currently ongoing are studies related to the downstream impact of dual STING / TLR4 activation in tumor cells. The compositions and methods of the appended claims are not limited in scope by the specific compositions and methods described herein, which are intended as illustrations of a few aspects of the claims and any compositions and methods that are functionally equivalent are intended to fall within the scope of the claims. Various modifications of the compositions and methods in addition to those shown and described herein are intended to fall within the scope of the appended claims. Further, while only certain representative compositions and method steps disclosed herein are specifically described, other combinations of the compositions and method steps also are intended to fall within the scope of the appended claims, even if not specifically recited. Thus, a combination of steps, elements, components, or constituents may be explicitly mentioned herein; however, other combinations of steps, elements, components, and constituents are included, even though not explicitly stated. The term “comprising” and variations thereof as used herein is used synonymously with the term “including” and variations thereof and are open, non-limiting terms. Although the terms “comprising” and “including” have been used herein to describe various embodiments, the terms “consisting essentially of” and “consisting of” can be used in place Attorney Docket No.11555-011WO1 of “comprising” and “including” to provide for more specific embodiments of the invention and are also disclosed. Other than in the examples, or where otherwise noted, all numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification and claims are to be understood at the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, to be construed in light of the number of significant digits and ordinary rounding approaches.

Claims

Attorney Docket No.11555-011WO1 WHAT IS CLAIMED IS:

1. A method of treating and / or preventing cancer in a subject, the method comprising administering to the subject a composition comprising a population of immunomodulatory lipid nanoparticles; wherein the immunomodulatory lipid nanoparticles comprise (a) a lipid-based nanoparticle carrier and (b) a (STING) pathway agonist and a (TLR4) agonist co- encapsulated within the lipid-based nanoparticle carrier.

2. The method of claim 1, wherein the population of immunomodulatory nanoparticles have an average particle size, as determined by dynamic light scattering (DLS), of from 25 nm to 250 nm, such as an average particle size of from 25 nm to 200 nm, an average particle size of from 25 nm to 150 nm, an average particle size of from 25 nm to 150 nm, or an average particle size of from 30 nm to 80 nm.

3. The method of any one of claims 1-2, wherein the composition is administered locally to the subject.

4. The method of any one of claims 1-3, wherein the composition is administered by subcutaneous injection, intradermal injection, or intramuscular injection.

5. The method of any one of claims 1-4, wherein the population of immunomodulatory lipid nanoparticles preferentially accumulates in a lymph node in the subject following administration.

6. The method of any one of claims 1-5, wherein the composition further comprises one or more tumor antigens.

7. The method of claim 6, wherein the one or more tumor antigens comprise one or more tumor antigenic peptides.

8. The method of claim 6, wherein the one or more tumor antigens comprise a nucleic acid encoding for a tumor antigen.Attorney Docket No.11555-011WO1 9. The method of any one of claims 1-8, wherein the composition further comprises a tumor lysate or an extract thereof.

10. The method of claim 9, wherein the tumor lysate is obtained from a biopsy or tissue sample collected from the subject.

11. The method of any one of claims 1-10, wherein the lipid-based nanoparticle carrier is selected from the group consisting of a liposome, a lipid nanoparticle, and a nanostructured lipid carrier (NLC).

12. The method of any one of claims 1-10, wherein the lipid-based nanoparticle carrier is a lipid nanoparticle.

13. The method of claim 12, wherein the lipid nanoparticle comprises one or more neutral lipids and one or more PEGylated lipids.

14. The method of any one of claims 12-13, wherein the lipid nanoparticle comprises 85 mol% to 99.5 mol% one or more neutral lipids; and 0.5 mol% to 15 mol% one or more PEGylated lipids.

15. The method of any one of claims 13-14, wherein the one more neutral lipids are selected from the group consisting of dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylethanolamine (DOPE), 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC), palmitoyloleoylphosphatidylcholine (POPC), egg phosphatidylcholine (EPC), distearoylphosphatidylcholine (DSPC), cholesterol, or any combination thereof.

16. The method of any one of claims 13-15, wherein the one more neutral lipids are selected from the group consisting of a PEG-ditetradecylacetamide, a PEG-myristoyl diglyceride, a PEG-diacylglycerol, a PEG dialkyloxypropyl, a PEG-phospholipid, a PEG- ceramide, PEG-DMG, PEG-DSPE, or any combination thereof.

17. The method of any one of claims 1-16, wherein the TLR4 agonist comprises a lipopolysaccharide (LPS) derivative or analog thereof.Attorney Docket No.11555-011WO1 18. The method of any one of claims 1-17, wherein the TLR4 agonist comprises a lipid A analog, variant, derivative, or mimetic.

19. The method of any one of claims 1-18, wherein the TLR4 agonist comprises monophosphoryl lipid A (MPLA).

20. The method of any one of claims 1-19, wherein the STING pathway agonist comprising a cyclic dinucleotide (CDN).

21. The method of claim 20, the CDN selected from the group consisting of cyclic dimeric guanosine monophosphate (cdGMP), cyclic dimeric adenosine monophosphate (cdAMP), and cyclic GMP-AMP (cGAMP).

22. The method of claim 21, the CDN comprising cyclic diguanylate monophosphate (cdGMP).

23. The method of any one of claims 1-22, wherein the immunomodulatory lipid nanoparticles further comprise one or more targeting moieties.

24. The method of claim 23, wherein the one or more targeting moieties are covalently linked to the immunomodulatory lipid nanoparticles.

25. The method of claim 24, wherein the one or more targeting moieties are covalently linked to PEGylated lipids present in the immunomodulatory lipid nanoparticles.

26. The method of any one of claims 23-25, wherein the one or more targeting moieties are selected from the group consisting of a peptide that binds to fibrin-fibronectin extracellular matrix, a peptide that binds to P-selectin, a peptide that binds to ^^^3 integrins, a peptide that binds to epidermal growth factor receptor (EGFR), or a combination thereof.

27. A method of treating and / or preventing cancer in a subject, the method comprising administering to the subject by subcutaneous injection, intradermal injection, orAttorney Docket No.11555-011WO1 intramuscular injection a composition comprising a population of immunomodulatory lipid nanoparticles; wherein the immunomodulatory lipid nanoparticles comprise (a) a lipid-based nanoparticle carrier and (b) a (STING) pathway agonist and a (TLR4) agonist co- encapsulated within the lipid-based nanoparticle carrier; and wherein the population of immunomodulatory lipid nanoparticles preferentially accumulates in a lymph node in the subject following administration.

28. The method of claim 27, wherein the population of immunomodulatory nanoparticles have an average particle size, as determined by dynamic light scattering (DLS), of from 30 nm to 80 nm.

29. The method of any one of claims 27-28, wherein the composition further comprises one or more tumor antigens.

30. The method of claim 29, wherein the one or more tumor antigens comprise one or more tumor antigenic peptides.

31. The method of claim 29, wherein the one or more tumor antigens comprise a nucleic acid encoding for a tumor antigen.

32. The method of any one of claims 27-31, wherein the composition further comprises a tumor lysate or an extract thereof.

33. The method of claim 32, wherein the tumor lysate is obtained from a biopsy or tissue sample collected from the subject.

34. The method of any one of claims 27-33, wherein the lipid-based nanoparticle carrier is selected from the group consisting of a liposome, a lipid nanoparticle, and a nanostructured lipid carrier (NLC).

35. The method of any one of claims 27-34, wherein the lipid-based nanoparticle carrier is a lipid nanoparticle.Attorney Docket No.11555-011WO1 36. The method of claim 35, wherein the lipid nanoparticle comprises one or more neutral lipids and one or more PEGylated lipids.

37. The method of any one of claims 35-36, wherein the lipid nanoparticle comprises 85 mol% to 99.5 mol% one or more neutral lipids; and 0.5 mol% to 15 mol% one or more PEGylated lipids.

38. The method of any one of claims 36-37, wherein the one more neutral lipids are selected from the group consisting of dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylethanolamine (DOPE), 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC), palmitoyloleoylphosphatidylcholine (POPC), egg phosphatidylcholine (EPC), distearoylphosphatidylcholine (DSPC), cholesterol, or any combination thereof.

39. The method of any one of claims 36-38, wherein the one more neutral lipids are selected from the group consisting of a PEG-ditetradecylacetamide, a PEG-myristoyl diglyceride, a PEG-diacylglycerol, a PEG dialkyloxypropyl, a PEG-phospholipid, a PEG- ceramide, PEG-DMG, PEG-DSPE, or any combination thereof.

40. The method of any one of claims 27-39, wherein the TLR4 agonist comprises a lipopolysaccharide (LPS) derivative or analog thereof.

41. The method of any one of claims 27-40, wherein the TLR4 agonist comprises a lipid A analog, variant, derivative, or mimetic.

42. The method of any one of claims 27-41, wherein the TLR4 agonist comprises monophosphoryl lipid A (MPLA).

43. The method of any one of claims 27-42, wherein the STING pathway agonist comprising a cyclic dinucleotide (CDN).Attorney Docket No.11555-011WO1 44. The method of claim 43, the CDN selected from the group consisting of cyclic dimeric guanosine monophosphate (cdGMP), cyclic dimeric adenosine monophosphate (cdAMP), and cyclic GMP-AMP (cGAMP).

45. The method of claim 44, the CDN comprising cyclic diguanylate monophosphate (cdGMP).

46. The method of any one of claims 27-45, wherein the immunomodulatory lipid nanoparticles further comprise one or more targeting moieties.

47. The method of claim 46, wherein the one or more targeting moieties are covalently linked to the immunomodulatory lipid nanoparticles.

48. A method of treating and / or preventing cancer metastasis in a subject, the method comprising administering to the subject a composition comprising a population of immunomodulatory lipid nanoparticles; wherein the immunomodulatory lipid nanoparticles comprise (a) a lipid-based nanoparticle carrier; (b) a (STING) pathway agonist and a (TLR4) agonist co-encapsulated within the lipid-based nanoparticle carrier; and (c) one or more targeting moieties are covalently linked to the immunomodulatory lipid nanoparticles.

49. The method of claim 48, wherein the cancer metastasis comprises a dormant metastasis.

50. The method of claim 48, wherein the cancer metastasis comprises an aggressive metastasis.

51. The method of any one of claims 48-50, wherein the one or more targeting moieties are covalently linked to PEGylated lipids present in the immunomodulatory lipid nanoparticles.

52. The method of any one of claims 48-51, wherein the one or more targeting moieties are selected from the group consisting of a peptide that binds to fibrin-fibronectinAttorney Docket No.11555-011WO1 extracellular matrix, a peptide that binds to P-selectin, a peptide that binds to ^^^3 integrins, a peptide that binds to epidermal growth factor receptor (EGFR), or a combination thereof.

53. The method of any one of claims 48-52, wherein the population of immunomodulatory nanoparticles have an average particle size, as determined by dynamic light scattering (DLS), of from 25 nm to 250 nm, such as an average particle size of from 25 nm to 200 nm, an average particle size of from 25 nm to 150 nm, an average particle size of from 25 nm to 150 nm, or an average particle size of from 30 nm to 80 nm.

54. The method of any one of claims 48-53, wherein the composition is administered systemically to the subject.

55. The method of any one of claims 48-54, wherein the composition is administered by intravenous injection.

56. The method of any one of claims 48-55, wherein the lipid-based nanoparticle carrier is selected from the group consisting of a liposome, a lipid nanoparticle, and a nanostructured lipid carrier (NLC).

57. The method of any one of claims 48-56, wherein the lipid-based nanoparticle carrier is a lipid nanoparticle.

58. The method of claim 57, wherein the lipid nanoparticle comprises one or more neutral lipids and one or more PEGylated lipids.

59. The method of any one of claims 57-58, wherein the lipid nanoparticle comprises 85 mol% to 99.5 mol% one or more neutral lipids; and 0.5 mol% to 15 mol% one or more PEGylated lipids.

60. The method of any one of claims 58-59, wherein the one more neutral lipids are selected from the group consisting of dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylethanolamine (DOPE), 1,2-Dioleoyl-sn-glycero-3-phosphocholineAttorney Docket No.11555-011WO1 (DOPC), palmitoyloleoylphosphatidylcholine (POPC), egg phosphatidylcholine (EPC), distearoylphosphatidylcholine (DSPC), cholesterol, or any combination thereof.

61. The method of any one of claims 58-60, wherein the one more neutral lipids are selected from the group consisting of a PEG-ditetradecylacetamide, a PEG-myristoyl diglyceride, a PEG-diacylglycerol, a PEG dialkyloxypropyl, a PEG-phospholipid, a PEG- ceramide, PEG-DMG, PEG-DSPE, or any combination thereof.

62. The method of any one of claims 48-61, wherein the TLR4 agonist comprises a lipopolysaccharide (LPS) derivative or analog thereof.

63. The method of any one of claims 48-62, wherein the TLR4 agonist comprises a lipid A analog, variant, derivative, or mimetic.

64. The method of any one of claims 48-63, wherein the TLR4 agonist comprises monophosphoryl lipid A (MPLA).

65. The method of any one of claims 48-64, wherein the STING pathway agonist comprising a cyclic dinucleotide (CDN).

66. The method of claim 65, the CDN selected from the group consisting of cyclic dimeric guanosine monophosphate (cdGMP), cyclic dimeric adenosine monophosphate (cdAMP), and cyclic GMP-AMP (cGAMP).

67. The method of claim 66, the CDN comprising cyclic diguanylate monophosphate (cdGMP).

68. A composition for treating and / or preventing cancer in a subject, the composition comprising a population of immunomodulatory lipid nanoparticles, wherein the immunomodulatory lipid nanoparticles comprise: (a) a lipid-based nanoparticle carrier; (b) a (STING) pathway agonist and a (TLR4) agonist co-encapsulated within the lipid-based nanoparticle carrier; andAttorney Docket No.11555-011WO1 (c) one or more targeting moieties covalently linked to the immunomodulatory lipid nanoparticles.

69. The composition of claim 68, wherein the one or more targeting moieties are covalently linked to PEGylated lipids present in the immunomodulatory lipid nanoparticles.

70. The method of any one of claims 68-69, wherein the one or more targeting moieties are selected from the group consisting of a peptide that binds to fibrin-fibronectin extracellular matrix, a peptide that binds to P-selectin, a peptide that binds to ^^^3integrins, a peptide that binds to epidermal growth factor receptor (EGFR), or a combination thereof.

71. A composition for treating and / or preventing cancer in a subject, the composition comprising a population of immunomodulatory lipid nanoparticles, wherein the immunomodulatory lipid nanoparticles comprise: (a) a lipid-based nanoparticle carrier; (b) a (STING) pathway agonist and a (TLR4) agonist co-encapsulated within the lipid-based nanoparticle carrier; and (c) one or more tumor antigens covalently linked to the immunomodulatory lipid nanoparticles.

72. The composition of claim 71, wherein the one or more tumor antigens are covalently linked to PEGylated lipids present in the immunomodulatory lipid nanoparticles.

73. The method of any one of claims 71-72, wherein the one or more tumor antigens comprise one or more tumor antigenic peptides.

74. A composition for treating and / or preventing cancer in a subject, the composition comprising (a) a population of immunomodulatory lipid nanoparticles and (b) one or more tumor antigens dissolved or dispersed in a pharmaceutically acceptable carrier; wherein the immunomodulatory lipid nanoparticles comprise: (i) a lipid-based nanoparticle carrier;Attorney Docket No.11555-011WO1 (i) a (STING) pathway agonist and a (TLR4) agonist co-encapsulated within the lipid-based nanoparticle carrier.

75. The method of claim 74, wherein the one or more tumor antigens comprise one or more tumor antigenic peptides.

76. The method of claim 74, wherein the one or more tumor antigens comprise a nucleic acid encoding for a tumor antigen.

77. A composition for treating and / or preventing cancer in a subject, the composition comprising (a) a population of immunomodulatory lipid nanoparticles and (b) tumor lysate or an extract thereof dissolved or dispersed in a pharmaceutically acceptable carrier; wherein the immunomodulatory lipid nanoparticles comprise: (i) a lipid-based nanoparticle carrier; (i) a (STING) pathway agonist and a (TLR4) agonist co-encapsulated within the lipid-based nanoparticle carrier.

78. The method of claim 77, wherein the tumor lysate is obtained from a biopsy or tissue sample collected from the subject.

79. The method of any one of claims 68-78, wherein the lipid-based nanoparticle carrier is selected from the group consisting of a liposome, a lipid nanoparticle, and a nanostructured lipid carrier (NLC).

80. The method of any one of claims 68-79, wherein the lipid-based nanoparticle carrier is a lipid nanoparticle.

81. The method of claim 80, wherein the lipid nanoparticle comprises one or more neutral lipids and one or more PEGylated lipids.

82. The method of any one of claims 80-81, wherein the lipid nanoparticle comprises 85 mol% to 99.5 mol% one or more neutral lipids; andAttorney Docket No.11555-011WO1 0.5 mol% to 15 mol% one or more PEGylated lipids.

83. The method of any one of claims 81-82, wherein the one more neutral lipids are selected from the group consisting of dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylethanolamine (DOPE), 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC), palmitoyloleoylphosphatidylcholine (POPC), egg phosphatidylcholine (EPC), distearoylphosphatidylcholine (DSPC), cholesterol, or any combination thereof.

84. The method of any one of claims 81-83, wherein the one more neutral lipids are selected from the group consisting of a PEG-ditetradecylacetamide, a PEG-myristoyl diglyceride, a PEG-diacylglycerol, a PEG dialkyloxypropyl, a PEG-phospholipid, a PEG- ceramide, PEG-DMG, PEG-DSPE, or any combination thereof.

85. The method of any one of claims 68-84, wherein the TLR4 agonist comprises a lipopolysaccharide (LPS) derivative or analog thereof.

86. The method of any one of claims 68-85, wherein the TLR4 agonist comprises a lipid A analog, variant, derivative, or mimetic.

87. The method of any one of claims 68-86, wherein the TLR4 agonist comprises monophosphoryl lipid A (MPLA).

88. The method of any one of claims 68-87, wherein the STING pathway agonist comprising a cyclic dinucleotide (CDN).

89. The method of claim 88, the CDN selected from the group consisting of cyclic dimeric guanosine monophosphate (cdGMP), cyclic dimeric adenosine monophosphate (cdAMP), and cyclic GMP-AMP (cGAMP).

90. The method of claim 89, the CDN comprising cyclic diguanylate monophosphate (cdGMP).