Augmentation of natural killer cell number and activity by senolytic therapies

Abstract

Compositions and methods for augmenting natural killer (NK) cell infiltration of tumors by removal of senescent cells. A tumor-bearing patient can be administered a senolytic agent together with one or more therapies that benefit from NK activation. Combination of senolytics with antibodies, senolytics with inducers of immunogenic cell death and combinations with CAR-NK cells.

Description

Immorta-ANKC-PCTAUGMENTATION OF NATURAL KILLER CELL NUMBER AND ACTIVITY BY SENOLYTIC THERAPIESCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims benefit of United States Provisional Application Serial No. 63 / 789,097, filed on April 15, 2025, entitled “Augmentation of Natural Killer Cell Number and Activity by Senolytic Therapies”, the contents of which are incorporated herein by reference in its entirety.FIELD OF THE INVENTION

[0002] The invention herein relates to cancer therapy and specifically encompasses compositions and methods for augmenting natural killer (NK) cell infiltration of tumors by removal of senescent cells.BACKGROUND OF THE INVENTION

[0003] Natural Killer (NK) cells play a crucial role in the body's immune defense against cancer by directly targeting and eliminating malignant cells. As a type of innate lymphoid cell, NK cells are uniquely equipped to recognize and kill cancer cells without prior sensitization, distinguishing them from other immune cells like T-cells. They identify cancer cells through a balance of activating and inhibitory signals, often detecting stress-induced molecules or the absence of "self" markers, such as MHC class I molecules, which cancer cells downregulate to evade detection. Once activated, NK cells release cytotoxic granules containing perforin and granzymes, which induce apoptosis in the target cancer cells, effectively halting tumor progression. Additionally, NK cells secrete cytokines like interferon-gamma, enhancing the immune response by recruiting and activating other immune cells to the tumor site. Their rapid response and ability to target a broad range of cancer cells make NK cells vital in early tumor suppression and a promising focus for immunotherapy advancements.

[0004] NK cells distinguish cancer cells from healthy cells through a sophisticated recognition system that hinges on the balance between activating and inhibitory signals. Healthy cells typically express major histocompatibility complex (MHC) class I molecules on their surface, which engage inhibitory receptors on NK cells, such as KIRs (killer immunoglobulin-like receptors), signaling that the cell is "self" and should be spared. Cancer cells, however, often downregulate MHC class I to evade T-cell detection, aImmorta-ANKC-PCTstrategy that inadvertently makes them vulnerable to NK cells, as the lack of inhibitory signals tips the balance toward activation. Additionally, cancer cells frequently express stress-induced ligands, such as MICA or MICB, which bind to activating receptors like NKG2D on NK cells, further triggering their cytotoxic response. This dual-signal mechanism allows NK cells to selectively target malignant cells while sparing healthy ones, though some cancers exploit this system by shedding these ligands or upregulating non-classical MHC molecules to suppress NK cell activity.

[0005] Cancer therapies that harness strong NK cell activity have emerged as promising strategies to enhance antitumor immunity, particularly in immunotherapy. Adoptive NK cell therapy, for instance, involves infusing patients with expanded or genetically modified NK cells to boost their tumor-killing capacity, showing efficacy in hematological malignancies like acute myeloid leukemia. Checkpoint inhibitors, such as antibodies targeting inhibitory receptors like PD-1 or NKG2A, can unleash NK cell activity by blocking suppressive signals, enhancing their ability to attack solid tumors. Additionally, cytokine-based treatments, such as IL-2 or IL- 15 administration, stimulate NK cell proliferation and cytotoxicity, amplifying their role in tumor elimination. Bispecific killer engagers (BiKEs) and trispecific killer engagers (TriKEs) are engineered molecules that bridge NK cells to cancer cells, directing their cytotoxic activity with precision, particularly in cancers like lymphoma. These therapies leverage NK cells’ innate ability to rapidly target cancer, offering synergistic potential when combined with other treatments like chemotherapy or monoclonal antibodies.SUMMARY OF THE INVENTION

[0006] A summary of the invention is provided below with respect to the following numbered aspects.

[0007] 1. A method of treating cancer comprising administration of one or more senolytic agents together with a therapy that benefits from NK cell activation.

[0008] 2. The method of aspect 1, wherein said senolytic agent is an immunotherapy.

[0009] 3. The method of aspect 1, wherein said senolytic agent is a small molecule.

[0010] 4. The method of aspect 1, wherein said senolytic agent is a peptide.

[0011] 5. The method of aspect 1, wherein said senolytic agent is an antibody.

[0012] 6. The method of aspect 1, wherein said senolytic agent is a molecule that induces RNA interference.Immorta-ANKC-PCT

[0013] 7. The method of aspect 1, wherein said senolytic agent is an antisense oligonucleotide.

[0014] 8. The method of aspect 1, wherein said senolytic agent is a circular RNA.

[0015] 9. The method of aspect 1, wherein said senolytic agent is a microRNA.

[0016] 10. The method of aspect 1, wherein said therapy that benefits from NK activation is a CAR-NK therapy.

[0017] 11. The method of aspect 1, wherein said therapy that benefits from NK activation is an antibody based therapy.

[0018] 12. The method of aspect 11, wherein said antibody based therapy is selected from a group comprising of: a) rituximab; b) trastuzumab; c) alemtuzumab; d) cetuximab; e) bevacizumab; f) panitumumab; g) ofatumumab; h) impilimumab; i) pertuzumab; j) Obinutuzumab; k) nivolumab; 1) pembrolizumab; m) dinutuximab; n) daratumumab; o) elotuzumab; p) necitumumab; q) ramucirumab; r) siltuximab; s) isatuximab; and t) tafasitamab.

[0019] 13. The method of aspect 1, herein said senolytic therapy is an immunotherapy.

[0020] 14. The method of aspect 13, wherein said senolytic immunotherapy involves stimulation of a T cell response against senescent cells.

[0021] 15. The method of aspect 14, wherein said T cell response is a cytolytic response.

[0022] 16. The method of aspect 15, wherein said T cell response is mediated by CD3 expressing T cells.

[0023] 17. The method of aspect 15, wherein said T cell response is mediated by CD4 expressing T cells.

[0024] 18. The method of aspect 15, wherein said T cell response is mediated by CD8 expressing T cells.

[0025] 19. The method of aspect 15, wherein said T cell response is mediated by perforin expressing T cells.

[0026] 20. The method of aspect 15, wherein said T cell response is mediated by granzyme B expressing T cells.

[0027] 21. The method of aspect 15, wherein said T cell response is mediated by granzyme K expressing T cells.

[0028] 22. The method of aspect 15, wherein said T cell response is mediated by CD25 expressing T cells.Immorta-ANKC-PCT

[0029] 23. The method of aspect 15, wherein said T cell response is mediated by CD127 expressing T cells.

[0030] 24. The method of aspect 15, wherein said T cell response is mediated by CD73 expressing T cells.

[0031] 25. The method of aspect 15, wherein said T cell response is mediated by CD105 expressing T cells.

[0032] 26. The method of aspect 15, wherein said T cell response is mediated by CD2 expressing T cells.

[0033] 27. The method of aspect 15, wherein said T cell response is mediated by CD5 expressing T cells.

[0034] 28. The method of aspect 15, wherein said T cell response is mediated by CD7 expressing T cells.

[0035] 29. The method of aspect 15, wherein said T cell response is mediated by CD44 expressing T cells.

[0036] 30. The method of aspect 15, wherein said T cell response is mediated by CD69 expressing T cells.

[0037] 31. The method of aspect 15, wherein said T cell response is mediated by CD45 RA expressing T cells.

[0038] 32. The method of aspect 15, wherein said T cell response is mediated by CD45 RO expressing T cells.

[0039] 33. The method of aspect 15, wherein said T cell response is mediated by CD62L expressing T cells.

[0040] 34. The method of aspect 15, wherein said T cell response is mediated by CCR7 expressing T cells.

[0041] 35. The method of aspect 15, wherein said T cell response is mediated by CD56 expressing T cells.

[0042] 36. The method of aspect 15, wherein said T cell response is mediated by CD57 expressing T cells.

[0043] 37. The method of aspect 15, wherein said T cell response is mediated by T cells secreting IL-2.

[0044] 38. The method of aspect 15, wherein said T cell response is mediated by T cells secreting IL-4.

[0045] 39. The method of aspect 15, wherein said T cell response is mediated by T cells secreting IL-7.Immorta-ANKC-PCT

[0046] 40. The method of aspect 15, wherein said T cell response is mediated by T cells secreting IL- 12.

[0047] 41. The method of aspect 15, wherein said T cell response is mediated by T cells secreting IL-15.

[0048] 42. The method of aspect 15, wherein said T cell response is mediated by T cells secreting IL- 17.

[0049] 43. The method of aspect 15, wherein said T cell response is mediated by T cells secreting IL-18.

[0050] 44. The method of aspect 15, wherein said T cell response is mediated by T cells secreting TNF-alpha.

[0051] 45. The method of aspect 15, wherein said T cell response is mediated by T cells secreting TNF-beta.

[0052] 46. The method of aspect 15, wherein said T cell response is mediated by T cells secreting interferon gamma.

[0053] 47. The method of aspect 15, wherein said T cell response is mediated by T cells secreting interferon alpha.

[0054] 48. The method of aspect 15, wherein said T cell response is mediated by T cells secreting interferon beta.

[0055] 49. The method of aspect 15, wherein said T cell response is mediated by T cells secreting interferon omega.

[0056] 50. The method of aspect 15, wherein said T cell response is mediated by T cells secreting interferon tau.

[0057] 51. The method of aspect 15, wherein said T cell response is mediated by T cells secreting TNF-alpha.

[0058] 52. The method of aspect 1, wherein said senolytic factor is substituted for a senomorphic factor.

[0059] 53. The method of aspect 1, wherein said senolytic factor is a bcl2 inhibitor.

[0060] 54. The method of aspect 1, wherein said senolytic factor is a bcl-XL inhibitor.

[0061] 55. The method of aspect 1, wherein said senolytic factor is quercetin.

[0062] 56. The method of aspect 1, wherein said senolytic factor is dasatinib.

[0063] 57. The method of aspect 1, wherein said senolytic factor is a combination of quercetin and dasatinib.

[0064] 58. The method of aspect 1, wherein said senolytic factor is valroic acid.Immorta-ANKC-PCT

[0065] 59. The method of aspect 1, wherein said senolytic factor is pterostilbene.

[0066] 60. The method of aspect 1, wherein said senolytic factor is procyanin Cl.

[0067] 61. The method of aspect 1, wherein said senolytic factor is reseveratrol.

[0068] 62. The method of aspect 1, wherein said senolytic factor is IVIG.

[0069] 63. The method of aspect 1, wherein said senolytic factor is imatinib.

[0070] 64. The method of aspect 1, wherein said senolytic factor is ABT263.

[0071] 65. The method of aspect 1, wherein said senolytic factor is a glutaminase inhibitor.

[0072] 66. The method of aspect 1, wherein said senolytic factor is ganciclovir.

[0073] 67. The method of aspect 52, wherein said senomorphic factor is rapamycin.

[0074] 68. The method of aspect 1, wherein said senolytic factor is metformin.

[0075] 69. The method of aspect 1, wherein said senolytic factor is chlorophyll.

[0076] 70. The method of aspect 1, wherein said senolytic factor is free DNA.

[0077] 71. The method of aspect 1, wherein said senolytic factor is ABT-737,

[0078] 72. The method of Aspect 1, wherein said senolytic factor is dasatinib.

[0079] 73. The method of Aspect 1, wherein said senolytic factor is quercetin,

[0080] 74. The method of Aspect 1, wherein said senolytic factor is fisetin.

[0081] 75. The method of Aspect 1, wherein said senolytic factor is navitoclax.

[0082] 76. The method of Aspect 1, wherein said senolytic factor is ABT-737,

[0083] 77. The method of Aspect 1, wherein said senolytic factor is piperlongumine.

[0084] 78. The method of Aspect 1, wherein said senolytic factor is curcumin.

[0085] 79. The method of Aspect 1, wherein said senolytic factor is ginkgetin.

[0086] 80. The method of Aspect 1, wherein said senolytic factor is periplocin,

[0087] 81. The method of Aspect 1, wherein said senolytic factor is oleandrin.

[0088] 82. The method of Aspect 1, wherein said senolytic factor is cianidanol.

[0089] 83. The method of Aspect 1, wherein said senolytic factor is ellagic acid,

[0090] 84. The method of Aspect 1, wherein said senolytic factor is eriodictyol,

[0091] 85. The method of Aspect 1, wherein said senolytic factor is kaempferol,

[0092] 86. The method of Aspect 1, wherein said senolytic factor is cyanidin.

[0093] 87. The method of Aspect 1, wherein said senolytic factor is parthenolide.

[0094] 88. The method of Aspect 1, wherein said senolytic factor is phloretin.

[0095] 89. The method of Aspect 1, wherein said senolytic factor is luteolin.

[0096] 90. The method of Aspect 1, wherein said senolytic factor is apigenin.

[0097] 91. The method of Aspect 1, wherein said senolytic factor is resveratrol.Immorta-ANKC-PCT

[0098] 92. The method of Aspect 1, wherein said senolytic factor is UBX0101.

[0099] 93. The method of Aspect 1, wherein said senolytic factor is UBX1325.

[0100] 94. The method of Aspect 1, wherein said senolytic factor is A1331852.

[0101] 95. The method of Aspect 1, wherein said senolytic factor is A1155463.

[0102] 96. The method of Aspect 1, wherein said senolytic factor is XL888.

[0103] 97. The method of Aspect 1, wherein said senolytic factor is nutlin-3a.

[0104] 98. The method of Aspect 1, wherein said senolytic factor is venetoclax.

[0105] 99. The method of Aspect 1, wherein said senolytic factor is digoxin.

[0106] 100. The method of Aspect 1, wherein said senolytic factor is ouabain.

[0107] 101. The method of Aspect 1, wherein said senolytic factor is proscillaridin A.

[0108] 102. The method of Aspect 1, wherein said senolytic factor is IBS001.

[0109] 103. The method of Aspect 1, wherein said senolytic factor is IBS002.

[0110] 104. The method of Aspect 1, wherein said senolytic factor is IBS003.

[0111] 105. The method of Aspect 1, wherein said senolytic factor is FOXO4-DRI.

[0112] 106. The method of Aspect 1, wherein said senolytic factor is SSK1.

[0113] 107. The method of Aspect 1, wherein said senolytic factor is Gal-NP- Navitoclax.

[0114] 108. The method of Aspect 1, wherein said senolytic factor is 25-hydroxy cholesterol.

[0115] 109. The method of Aspect 1, wherein said senolytic factor is brefeldin A.

[0116] 110. The method of Aspect 1, wherein said senolytic factor is rapamycin.

[0117] 111. The method of Aspect 1, wherein said senolytic factor is metformin.

[0118] 112. The method of Aspect 1, wherein said senolytic factor is azithromycin.

[0119] 113. The method of Aspect 1, wherein said senolytic factor is roxithromycin.

[0120] 114. The method of Aspect 1, wherein said senolytic factor is geldanamycin.

[0121] 115. The method of Aspect 1, wherein said senolytic factor is tanespimycin.

[0122] 116. The method of Aspect 1, wherein said senolytic factor is alvespimycin.

[0123] 117. The method of Aspect 1, wherein said senolytic factor is celastrol.

[0124] 118. The method of Aspect 1, wherein said senolytic factor is withaferin A.

[0125] 119. The method of Aspect 1, wherein said senolytic factor is etoposide.

[0126] 120. The method of Aspect 1, wherein said senolytic factor is trametinib.

[0127] 121. The method of Aspect 1, wherein said senolytic factor is selumetinib.

[0128] 122. The method of Aspect 1, wherein said senolytic factor is myricetin.Immorta-ANKC-PCT

[0129] 123. The method of Aspect 1, wherein said senolytic factor is genistein.

[0130] 124. A method of treating cancer comprising administration of one or more senolytics together with one or more histone deacetylase inhibitors.

[0131] 125. The method of aspect 124, wherein said histone deacetylase inhibitor is

[0132] 125. The method of aspect 124, wherein said histone deacetylase inhibitor is vorinostat.

[0133] 126. The method of aspect 124, wherein said histone deacetylase inhibitor is romidepsin.

[0134] 127. The method of aspect 124, wherein said histone deacetylase inhibitor is panobinostat.

[0135] 128. The method of aspect 124, wherein said histone deacetylase inhibitor is belinostat.

[0136] 129. The method of aspect 124, wherein said histone deacetylase inhibitor is entinostat.

[0137] 130. The method of aspect 124, wherein said histone deacetylase inhibitor is mocetinostat.

[0138] 131. The method of aspect 124, wherein said histone deacetylase inhibitor is a hydroxamic acid derivative.

[0139] 132. The method of aspect 131, wherein said hydroxamic acid derivative is selected from the group consisting of vorinostat, panobinostat, belinostat, and trichostatin A.

[0140] 133. The method of aspect 124, wherein said histone deacetylase inhibitor is a benzamide derivative.

[0141] 134. The method of aspect 133, wherein said benzamide derivative is selected from the group consisting of entinostat and mocetinostat.

[0142] 135. The method of aspect 124, wherein said histone deacetylase inhibitor is a cyclic peptide.

[0143] 136. The method of aspect 135, wherein said cyclic peptide is romidepsin.

[0144] 137. The method of aspect 124, wherein said histone deacetylase inhibitor is a short-chain fatty acid.

[0145] 138. The method of aspect 137, wherein said short-chain fatty acid is selected from the group consisting of valproic acid and sodium butyrate.

[0146] 139. The method of aspect 124, wherein said histone deacetylase inhibitor selectively inhibits HDAC1.Immorta-ANKC-PCT

[0147] 140. The method of aspect 124, wherein said histone deacetylase inhibitor selectively inhibits HDAC2.

[0148] 141. The method of aspect 124, wherein said histone deacetylase inhibitor selectively inhibits HDAC3.

[0149] 142. The method of aspect 124, wherein said histone deacetylase inhibitor selectively inhibits HDAC6.

[0150] 143. The method of aspect 124, wherein said histone deacetylase inhibitor is a pan-HDAC inhibitor.

[0151] 144. The method of aspect 143, wherein said pan-HDAC inhibitor is selected from the group consisting of vorinostat, panobinostat, and belinostat.

[0152] 145. The method of aspect 124, wherein said histone deacetylase inhibitor is administered orally.

[0153] 146. The method of aspect 124, wherein said histone deacetylase inhibitor is administered intravenously.

[0154] 147. The method of aspect 124, wherein said histone deacetylase inhibitor is administered topically.

[0155] 148. The method of aspect 124, wherein said histone deacetylase inhibitor is administered at a dose of about 1 mg to about 1000 mg per day.

[0156] 149. The method of aspect 148, wherein said dose is about 50 mg to about 400 mg per day.

[0157] 150. The method of aspect 124, wherein said histone deacetylase inhibitor is administered once daily.

[0158] 151. The method of aspect 124, wherein said histone deacetylase inhibitor is administered twice daily.

[0159] 152. The method of aspect 124, wherein said histone deacetylase inhibitor is administered in a pharmaceutical composition comprising a pharmaceutically acceptable carrier.

[0160] 153. The method of aspect 152, wherein said pharmaceutical composition is a tablet.

[0161] 154. The method of aspect 152, wherein said pharmaceutical composition is a capsule.

[0162] 155. The method of aspect 152, wherein said pharmaceutical composition is a liquid formulation.Immorta-ANKC-PCT

[0163] 156. The method of aspect 124, wherein said method further comprises administering a second therapeutic agent.

[0164] 157. The method of aspect 156, wherein said second therapeutic agent is a chemotherapeutic agent.

[0165] 158. The method of aspect 157, wherein said chemotherapeutic agent is selected from the group consisting of cisplatin, doxorubicin, and paclitaxel.

[0166] 159. The method of aspect 156, wherein said second therapeutic agent is an immunotherapy agent.

[0167] 160. The method of aspect 159, wherein said immunotherapy agent is a checkpoint inhibitor.

[0168] 161. The method of aspect 160, wherein said checkpoint inhibitor is selected from the group consisting of pembrolizumab, nivolumab, and atezolizumab.

[0169] 162. The method of aspect 124, wherein said method treats a cancer.

[0170] 163. The method of aspect 162, wherein said cancer is cutaneous T-cell lymphoma.

[0171] 164. The method of aspect 162, wherein said cancer is multiple myeloma.

[0172] 165. The method of aspect 162, wherein said cancer is a solid tumor.

[0173] 166. The method of aspect 165, wherein said solid tumor is selected from the group consisting of lung cancer, breast cancer, and colorectal cancer.

[0174] 167. The method of aspect 124, wherein said method treats a neurodegen erative disorder.

[0175] 168. The method of aspect 167, wherein said neurodegenerative disorder is selected from the group consisting of Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease.

[0176] 169. The method of aspect 124, wherein said method treats an inflammatory disorder.

[0177] 170. The method of aspect 169, wherein said inflammatory disorder is selected from the group consisting of rheumatoid arthritis and inflammatory bowel disease.

[0178] 171. The method of aspect 124, wherein said histone deacetylase inhibitor is a compound of Formula I:[wherein Formula I defines a generic chemical structure for HD AC inhibitors, e.g., a hydroxamic acid scaffold with variable R groups].Immorta-ANKC-PCT

[0179] 172. The method of aspect 171, wherein said compound of Formula I has a substituent R1 selected from the group consisting of hydrogen, alkyl, and aryl.

[0180] 173. The method of aspect 124, wherein said histone deacetylase inhibitor is a compound of Formula II:[wherein Formula II defines a benzamide scaffold with variable substituents],

[0181] 174. The method of aspect 173, wherein said compound of Formula II has a substituent R2 selected from the group consisting of halogen, nitro, and amino.

[0182] 175. The method of aspect 124, wherein said histone deacetylase inhibitor is administered in combination with radiation therapy.

[0183] 176. The method of aspect 124, wherein said histone deacetylase inhibitor is administered to a patient having a biomarker indicative of HD AC overexpression.

[0184] 177. The method of aspect 176, wherein said biomarker is selected from the group consisting of HDAC1, HDAC2, and HDAC3 gene expression levels.

[0185] 178. The method of aspect 124, wherein said histone deacetylase inhibitor is administered in a pulsatile dosing regimen.

[0186] 179. The method of aspect 178, wherein said pulsatile dosing regimen comprises administering said inhibitor for 5 days followed by 2 days without administration.

[0187] 180. The method of aspect 124, wherein said histone deacetylase inhibitor is formulated as a sustained-release composition.

[0188] 181. The method of aspect 124, wherein said histone deacetylase inhibitor is formulated as an immediate-release composition.

[0189] 182. The method of aspect 124, wherein said histone deacetylase inhibitor is administered to a pediatric patient.

[0190] 183. The method of aspect 124, wherein said histone deacetylase inhibitor is administered to an adult patient.

[0191] 184. The method of aspect 124, wherein said histone deacetylase inhibitor is administered in a neoadjuvant setting.

[0192] 185. The method of aspect 124, wherein said histone deacetylase inhibitor is administered in an adjuvant setting.

[0193] 186. The method of aspect 124, wherein said histone deacetylase inhibitor is administered to a patient with a genetic mutation associated with HD AC activity.

[0194] 187. The method of aspect 186, wherein said genetic mutation is in a gene selected from the group consisting of TP53, PTEN, and MYC.Immorta-ANKC-PCT

[0195] 188. The method of aspect 124, wherein said histone deacetylase inhibitor is administered via a transdermal patch.

[0196] 189. The method of aspect 124, wherein said histone deacetylase inhibitor is administered via inhalation.

[0197] 190. The method of aspect 124, wherein said histone deacetylase inhibitor is administered in a nanoparticle formulation.

[0198] 191. The method of aspect 124, wherein said histone deacetylase inhibitor is conjugated to a targeting moiety.

[0199] 192. The method of aspect 191, wherein said targeting moiety is an antibody specific to a tumor-associated antigen.

[0200] 193. The method of aspect 124, wherein said histone deacetylase inhibitor is administered to a patient with a history of chemotherapy resistance.

[0201] 194. The method of aspect 124, wherein said histone deacetylase inhibitor is administered in a metronomic dosing schedule.

[0202] 195. The method of aspect 124, wherein said histone deacetylase inhibitor is administered in combination with a proteasome inhibitor.

[0203] 196. The method of aspect 195, wherein said proteasome inhibitor is bortezomib.

[0204] 197. The method of aspect 124, wherein said histone deacetylase inhibitor is administered to a patient with a hematologic malignancy.

[0205] 198. The method of aspect 197, wherein said hematologic malignancy is selected from the group consisting of leukemia, lymphoma, and myelodysplastic syndrome.

[0206] 199. The method of aspect 124, wherein said histone deacetylase inhibitor is administered in a liposomal formulation.

[0207] 200. The method of aspect 124, wherein said histone deacetylase inhibitor is administered in a regimen that achieves a plasma concentration of about 0.1 μM to about 10 μM.

[0208] 201. The method of aspect 124, wherein said histone deacetylase inhibitor is administered to a patient with a tumor exhibiting epigenetic dysregulation.

[0209] 202. The method of aspect 201, wherein said epigenetic dysregulation comprises hypermethylation of a tumor suppressor gene.

[0210] 203. The method of aspect 124, wherein said histone deacetylase inhibitor is administered in combination with a DNA methyltransferase inhibitor.Immorta-ANKC-PCT

[0211] 204. The method of aspect 203, wherein said DNA methyltransferase inhibitor is azacitidine.

[0212] 205. The method of aspect 124, wherein said histone deacetylase inhibitor is administered to a patient with a viral infection.

[0213] 206. The method of aspect 205, wherein said viral infection is caused by a virus selected from the group consisting of HIV, EBV, and CMV.

[0214] 207. The method of aspect 124, wherein said histone deacetylase inhibitor is administered in a combination therapy with a kinase inhibitor.

[0215] 208. The method of aspect 207, wherein said kinase inhibitor is selected from the group consisting of imatinib, erlotinib, and sorafenib.

[0216] 209. The method of aspect 124, wherein said histone deacetylase inhibitor is administered in a regimen guided by pharmacodynamic monitoring.

[0217] 210. The method of aspect 209, wherein said pharmacodynamic monitoring comprises measuring histone acetylation levels in peripheral blood mononuclear cells.

[0218] 211. The method of aspect 124, wherein said histone deacetylase inhibitor is administered to a patient with a rare disease associated with HD AC dysregulation.

[0219] 212. The method of aspect 211, wherein said rare disease is Rubinstein- Taybi syndrome.

[0220] 213. The method of aspect 124, wherein said histone deacetylase inhibitor is administered in a regimen that minimizes toxicity.

[0221] 214. The method of aspect 213, wherein said regimen includes dose adjustments based on patient liver function.

[0222] 215. The method of aspect 124, wherein said histone deacetylase inhibitor is a synthetic analog of a naturally occurring HD AC inhibitor.

[0223] 216. The method of aspect 215, wherein said naturally occurring HD AC inhibitor is trapoxin.

[0224] 217. The method of aspect 124, wherein said histone deacetylase inhibitor is administered in a regimen that includes a loading dose followed by a maintenance dose.

[0225] 218. The method of aspect 124, wherein said histone deacetylase inhibitor is administered to a patient with a sarcoma.

[0226] 219. The method of aspect 124, wherein said histone deacetylase inhibitor is administered in a regimen that includes periodic imaging to monitor treatment response.

[0227] 220. The method of aspect 124, wherein said histone deacetylase inhibitor is administered in combination with a metabolic modulator.Immorta-ANKC-PCT

[0228] 221. The method of aspect 220, wherein said metabolic modulator is metformin.

[0229] 222. The method of aspect 124, wherein said histone deacetylase inhibitor is administered to a patient with a brain tumor.

[0230] 223. The method of aspect 222, wherein said brain tumor is glioblastoma.

[0231] 224. A method of treating cancer through combination of immunotherapy together with senolytics for activation of NK cells and treatment of cancer.

[0232] 225. The method of aspect 224, wherein said immunotherapy comprises a checkpoint inhibitor.

[0233] 226. The method of aspect 225, wherein said checkpoint inhibitor is an anti- PD-1 antibody.

[0234] 227. The method of aspect 226, wherein said anti-PD-1 antibody is pembrolizumab.

[0235] 228. The method of aspect 226, wherein said anti-PD-1 antibody is nivolumab.

[0236] 229. The method of aspect 225, wherein said checkpoint inhibitor is an anti- PD-L1 antibody.

[0237] 230. The method of aspect 229, wherein said anti-PD-Ll antibody is atezolizumab.

[0238] 231. The method of aspect 229, wherein said anti-PD-Ll antibody is durvalumab.

[0239] 232. The method of aspect 225, wherein said checkpoint inhibitor is an anti- CTLA-4 antibody.

[0240] 233. The method of aspect 232, wherein said anti-CTLA-4 antibody is ipilimumab.

[0241] 234. The method of aspect 224, wherein said immunotherapy comprises a cytokine therapy.

[0242] 235. The method of aspect 234, wherein said cytokine therapy comprises interleukin-2 (IL-2).

[0243] 236. The method of aspect 234, wherein said cytokine therapy comprises interleukin-15 (IL-15).

[0244] 237. The method of aspect 224, wherein said immunotherapy comprises an NK cell engager.Immorta-ANKC-PCT

[0245] 238. The method of aspect 237, wherein said NK cell engager is a bispecific antibody targeting CD 16 and a tumor-associated antigen.

[0246] 239. The method of aspect 224, wherein said immunotherapy comprises an adoptive cell therapy.

[0247] 240. The method of aspect 239, wherein said adoptive cell therapy comprises autologous NK cells.

[0248] 241. The method of aspect 239, wherein said adoptive cell therapy comprises allogeneic NK cells.

[0249] 242. The method of aspect 224, wherein said senolytic agent comprises a BCL-2 family inhibitor.

[0250] 243. The method of aspect 242, wherein said BCL-2 family inhibitor is navitoclax.

[0251] 244. The method of aspect 242, wherein said BCL-2 family inhibitor is venetoclax.

[0252] 245. The method of aspect 224, wherein said senolytic agent comprises a tyrosine kinase inhibitor.

[0253] 246. The method of aspect 245, wherein said tyrosine kinase inhibitor is dasatinib.

[0254] 247. The method of aspect 224, wherein said senolytic agent comprises a flavonoid.

[0255] 248. The method of aspect 247, wherein said flavonoid is quercetin.

[0256] 249. The method of aspect 224, wherein said senolytic agent comprises a HSP90 inhibitor.

[0257] 250. The method of aspect 249, wherein said HSP90 inhibitor is 17-AAG (tanespimycin).

[0258] 251. The method of aspect 224, wherein said senolytic agent comprises a MDM2 inhibitor.

[0259] 252. The method of aspect 251, wherein said MDM2 inhibitor is idasanutlin.

[0260] 253. The method of aspect 224, wherein said immunotherapy and said senolytic agent are administered sequentially.

[0261] 254. The method of aspect 253, wherein said senolytic agent is administered prior to said immunotherapy.

[0262] 255. The method of aspect 253, wherein said immunotherapy is administered prior to said senolytic agent.Immorta-ANKC-PCT

[0263] 256. The method of aspect 224, wherein said immunotherapy and said senolytic agent are administered simultaneously.

[0264] 257. The method of aspect 224, wherein said immunotherapy is administered intravenously.

[0265] 258. The method of aspect 224, wherein said senolytic agent is administered orally.

[0266] 259. The method of aspect 224, wherein said immunotherapy is administered at a dose of about 1 mg / kg to about 10 mg / kg.

[0267] 260. The method of aspect 224, wherein said senolytic agent is administered at a dose of about 0.1 mg / kg to about 50 mg / kg.

[0268] 261. The method of aspect 224, wherein said method increases NK cell cytotoxicity by at least 20% compared to immunotherapy alone.

[0269] 262. The method of aspect 224, wherein said method increases NK cell expression of CD107a.

[0270] 263. The method of aspect 224, wherein said method increases NK cell secretion of interferon-gamma (IFN-γ).

[0271] 264. The method of aspect 224, wherein said cancer is a solid tumor.

[0272] 265. The method of aspect 264, wherein said solid tumor is selected from the group consisting of lung cancer, breast cancer, colorectal cancer, and melanoma.

[0273] 266. The method of aspect 224, wherein said cancer is a hematologic malignancy.

[0274] 267. The method of aspect 266, wherein said hematologic malignancy is selected from the group consisting of leukemia, lymphoma, and multiple myeloma.

[0275] 268. The method of aspect 224, wherein said method treats metastatic cancer.

[0276] 269. The method of aspect 224, wherein said method is administered in a neoadjuvant setting.

[0277] 270. The method of aspect 224, wherein said method is administered in an adjuvant setting.

[0278] 271. The method of aspect 224, wherein said immunotherapy and said senolytic agent are formulated in a single pharmaceutical composition.

[0279] 272. The method of aspect 271, wherein said pharmaceutical composition is a tablet.Immorta-ANKC-PCT

[0280] 273. The method of aspect 271, wherein said pharmaceutical composition is an injectable solution.

[0281] 274. The method of aspect 224, wherein said method further comprises administering a chemotherapeutic agent.

[0282] 275. The method of aspect 274, wherein said chemotherapeutic agent is selected from the group consisting of cisplatin, doxorubicin, and paclitaxel.

[0283] 276. The method of aspect 224, wherein said method further comprises administering radiation therapy.

[0284] 277. The method of aspect 224, wherein said method is administered to a patient with a biomarker indicative of senescent cell accumulation.

[0285] 278. The method of aspect 277, wherein said biomarker is selected from the group consisting of p16INK4a, p21CIP1, and senescence-associated P-galactosidase (SA-β-gal).

[0286] 279. The method of aspect 224, wherein said method is administered to a patient with a biomarker indicative of NK cell dysfunction.

[0287] 280. The method of aspect 279, wherein said biomarker is reduced expression of CD16 or NKG2D.

[0288] 281. The method of aspect 224, wherein said senolytic agent selectively targets senescent cells expressing a senescence-associated secretory phenotype (SASP).

[0289] 282. The method of aspect 224, wherein said immunotherapy comprises a monoclonal antibody targeting a tumor antigen.

[0290] 283. The method of aspect 282, wherein said monoclonal antibody is selected from the group consisting of trastuzumab and cetuximab.

[0291] 284. The method of aspect 224, wherein said senolytic agent is administered in a pulsatile dosing regimen.

[0292] 285. The method of aspect 284, wherein said pulsatile dosing regimen comprises administering said senolytic agent for 3 days followed by 11 days without administration.

[0293] 286. The method of aspect 224, wherein said immunotherapy is administered in a metronomic dosing schedule.

[0294] 287. The method of aspect 224, wherein said method reduces the tumor microenvironment’s immunosuppressive activity.

[0295] 288. The method of aspect 224, wherein said method enhances NK cell infiltration into the tumor microenvironment.Immorta-ANKC-PCT

[0296] 289. The method of aspect 224, wherein said senolytic agent is formulated as a nanoparticle.

[0297] 290. The method of aspect 224, wherein said immunotherapy is conjugated to a targeting moiety.

[0298] 291. The method of aspect 290, wherein said targeting moiety is specific to a tumor-associated antigen.

[0299] 292. The method of aspect 224, wherein said method is administered to a patient with a history of immunotherapy resistance.

[0300] 293. The method of aspect 224, wherein said method is administered to a patient with a genetic mutation associated with senescence.

[0301] 294. The method of aspect 293, wherein said genetic mutation is in a gene selected from the group consisting of TP53, PTEN, and CDKN2A.

[0302] 295. The method of aspect 224, wherein said senolytic agent is a peptide-based senolytic.

[0303] 296. The method of aspect 295, wherein said peptide-based senolytic targets FOXO4.

[0304] 297. The method of aspect 224, wherein said immunotherapy comprises a cancer vaccine.

[0305] 298. The method of aspect 297, wherein said cancer vaccine is a peptide-based vaccine targeting a tumor neoantigen.

[0306] 299. The method of aspect 224, wherein said method is administered to a patient with a tumor exhibiting high SASP expression.

[0307] 300. The method of aspect 224, wherein said method is guided by pharmacodynamic monitoring of NK cell activation.

[0308] 301. The method of aspect 300, wherein said pharmacodynamic monitoring comprises measuring NK cell expression of CD107a or IFN-γ.

[0309] 302. The method of aspect 224, wherein said senolytic agent is administered via inhalation.

[0310] 303. The method of aspect 224, wherein said immunotherapy is administered via a transdermal patch.

[0311] 304. The method of aspect 224, wherein said method treats a cancer resistant to checkpoint inhibitors.

[0312] 305. The method of aspect 224, wherein said method increases the ratio of effector NK cells to regulatory T cells in the tumor microenvironment.Immorta-ANKC-PCT

[0313] 306. The method of aspect 224, wherein said senolytic agent is a natural compound.

[0314] 307. The method of aspect 306, wherein said natural compound is fisetin.

[0315] 308. The method of aspect 224, wherein said immunotherapy comprises an oncolytic virus.

[0316] 309. The method of aspect 308, wherein said oncolytic virus is talimogene laherparepvec.

[0317] 310. The method of aspect 224, wherein said method is administered to a pediatric patient.

[0318] 311. The method of aspect 224, wherein said method is administered to an adult patient.

[0319] 312. The method of aspect 224, wherein said senolytic agent is administered in a liposomal formulation.

[0320] 313. The method of aspect 224, wherein said immunotherapy is administered in a regimen that achieves a plasma concentration of about 0.1 pg / mL to about 10 pg / mL.

[0321] 314. The method of aspect 224, wherein said senolytic agent is administered in a regimen that achieves a plasma concentration of about 0.1 μM to about 100 μM.

[0322] 315. The method of aspect 224, wherein said method is administered in combination with a kinase inhibitor.

[0323] 316. The method of aspect 315, wherein said kinase inhibitor is selected from the group consisting of imatinib and sorafenib.

[0324] 317. The method of aspect 224, wherein said method treats a cancer with a high tumor mutational burden.

[0325] 318. The method of aspect 224, wherein said method is administered to a patient with a tumor exhibiting microsatellite instability.

[0326] 319. The method of aspect 224, wherein said senolytic agent is a synthetic analog of a naturally occurring senolytic.

[0327] 320. The method of aspect 319, wherein said naturally occurring senolytic is quercetin.

[0328] 321. The method of aspect 224, wherein said immunotherapy comprises a STING agonist.

[0329] 322. The method of aspect 321, wherein said STING agonist is ADU-S100.

[0330] 323. The method of aspect 224, wherein said method is administered in a regimen that includes periodic imaging to monitor tumor response.Immorta-ANKC-PCT

[0331] 324. The method of aspect 224, wherein said method is administered in combination with a metabolic modulator.

[0332] 325. A method of treating cancer by combined administration of one or more agents that stimulates NK cell activity together with one or more senolytics together with one or more agents that suppress or inactivate T regulatory cells.

[0333] 325. A method of treating cancer in a subject, comprising administering to the subject a combination of one or more agents that stimulates natural killer (NK) cell activity, one or more senolytic agents, and one or more agents that suppress or inactivate T regulatory cells.

[0334] 326. The method of aspect 325, wherein said agent that stimulates NK cell activity comprises a cytokine.

[0335] 327. The method of aspect 326, wherein said cytokine is interleukin-2 (IL-2).

[0336] 328. The method of aspect 326, wherein said cytokine is interleukin-15 (IL-15).

[0337] 329. The method of aspect 326, wherein said cytokine is interleukin-21 (IL- 21).

[0338] 330. The method of aspect 325, wherein said agent that stimulates NK cell activity comprises an NK cell engager.

[0339] 331. The method of aspect 330, wherein said NK cell engager is a bispecific antibody targeting CD 16 and a tumor-associated antigen.

[0340] 332. The method of aspect 331, wherein said tumor-associated antigen is HER2.

[0341] 333. The method of aspect 331, wherein said tumor-associated antigen is EGFR.

[0342] 334. The method of aspect 325, wherein said agent that stimulates NK cell activity comprises a checkpoint inhibitor.

[0343] 335. The method of aspect 334, wherein said checkpoint inhibitor targets PD-1.

[0344] 336. The method of aspect 335, wherein said checkpoint inhibitor is pembrolizumab.

[0345] 337. The method of aspect 335, wherein said checkpoint inhibitor is nivolumab.

[0346] 338. The method of aspect 334, wherein said checkpoint inhibitor targets PD-L1.Immorta-ANKC-PCT

[0347] 339. The method of aspect 338, wherein said checkpoint inhibitor is atezolizumab.

[0348] 340. The method of aspect 325, wherein said agent that stimulates NK cell activity comprises an adoptive NK cell therapy.

[0349] 341. The method of aspect 340, wherein said adoptive NK cell therapy comprises autologous NK cells.

[0350] 342. The method of aspect 340, wherein said adoptive NK cell therapy comprises allogeneic NK cells.

[0351] 343. The method of aspect 325, wherein said senolytic agent comprises a BCL-2 family inhibitor.

[0352] 344. The method of aspect 343, wherein said BCL-2 family inhibitor is navitoclax.

[0353] 345. The method of aspect 343, wherein said BCL-2 family inhibitor is venetoclax.

[0354] 346. The method of aspect 325, wherein said senolytic agent comprises a tyrosine kinase inhibitor.

[0355] 347. The method of aspect 346, wherein said tyrosine kinase inhibitor is dasatinib.

[0356] 348. The method of aspect 325, wherein said senolytic agent comprises a flavonoid.

[0357] 349. The method of aspect 348, wherein said flavonoid is quercetin.

[0358] 350. The method of aspect 348, wherein said flavonoid is fisetin.

[0359] 351. The method of aspect 325, wherein said senolytic agent comprises an HSP90 inhibitor.

[0360] 352. The method of aspect 351, wherein said HSP90 inhibitor is tanespimycin (17-AAG).

[0361] 353. The method of aspect 325, wherein said senolytic agent comprises an MDM2 inhibitor.

[0362] 354. The method of aspect 353, wherein said MDM2 inhibitor is idasanutlin.

[0363] 355. The method of aspect 325, wherein said agent that suppresses or inactivates T regulatory cells comprises a checkpoint inhibitor.

[0364] 356. The method of aspect 355, wherein said checkpoint inhibitor targets CTLA-4.Immorta-ANKC-PCT

[0365] 357. The method of aspect 356, wherein said checkpoint inhibitor is ipilimumab.

[0366] 358. The method of aspect 355, wherein said checkpoint inhibitor targets LAG-3.

[0367] 359. The method of aspect 358, wherein said checkpoint inhibitor is relatlimab.

[0368] 360. The method of aspect 325, wherein said agent that suppresses or inactivates T regulatory cells comprises an anti-CD25 antibody.

[0369] 361. The method of aspect 360, wherein said anti-CD25 antibody is daclizumab.

[0370] 362. The method of aspect 325, wherein said agent that suppresses or inactivates T regulatory cells comprises a small molecule inhibitor.

[0371] 363. The method of aspect 362, wherein said small molecule inhibitor targets FOXP3 signaling.

[0372] 364. The method of aspect 362, wherein said small molecule inhibitor is a PI3K inhibitor.

[0373] 365. The method of aspect 364, wherein said PI3K inhibitor is idelalisib.

[0374] 366. The method of aspect 325, wherein said agent that suppresses or inactivates T regulatory cells comprises an IDO inhibitor.

[0375] 367. The method of aspect 366, wherein said IDO inhibitor is epacadostat.

[0376] 368. The method of aspect 325, wherein said combination is administered sequentially.

[0377] 369. The method of aspect 368, wherein said senolytic agent is administered prior to said agent that stimulates NK cell activity and said agent that suppresses T regulatory cells.

[0378] 370. The method of aspect 368, wherein said agent that suppresses T regulatory cells is administered prior to said senolytic agent and said agent that stimulates NK cell activity.

[0379] 371. The method of aspect 325, wherein said combination is administered simultaneously.

[0380] 372. The method of aspect 325, wherein said agent that stimulates NK cell activity is administered intravenously.

[0381] 373. The method of aspect 325, wherein said senolytic agent is administered orally.Immorta-ANKC-PCT

[0382] 374. The method of aspect 325, wherein said agent that suppresses T regulatory cells is administered subcutaneously.

[0383] 375. The method of aspect 325, wherein said agent that stimulates NK cell activity is administered at a dose of about 0.1 mg / kg to about 10 mg / kg.

[0384] 376. The method of aspect 325, wherein said senolytic agent is administered at a dose of about 0.1 mg / kg to about 50 mg / kg.

[0385] 377. The method of aspect 325, wherein said agent that suppresses T regulatory cells is administered at a dose of about 0.5 mg / kg to about 15 mg / kg.

[0386] 378. The method of aspect 325, wherein said method increases NK cell cytotoxicity by at least 20% compared to administration of the NK cell-stimulating agent alone.

[0387] 379. The method of aspect 325, wherein said method reduces T regulatory cell activity by at least 30% compared to baseline.

[0388] 380. The method of aspect 325, wherein said method decreases the proportion of senescent cells in the tumor microenvironment by at least 25%.

[0389] 381. The method of aspect 325, wherein said method increases NK cell expression of CD107a.

[0390] 382. The method of aspect 325, wherein said method increases NK cell secretion of interferon-gamma (IFN-γ).

[0391] 383. The method of aspect 325, wherein said method reduces expression of FOXP3 in T regulatory cells.

[0392] 384. The method of aspect 325, wherein said cancer is a solid tumor.

[0393] 385. The method of aspect 384, wherein said solid tumor is selected from the group consisting of lung cancer, breast cancer, colorectal cancer, and melanoma.

[0394] 386. The method of aspect 384, wherein said solid tumor is pancreatic cancer.

[0395] 387. The method of aspect 384, wherein said solid tumor is prostate cancer.

[0396] 388. The method of aspect 325, wherein said cancer is a hematologic malignancy.

[0397] 389. The method of aspect 388, wherein said hematologic malignancy is selected from the group consisting of leukemia, lymphoma, and multiple myeloma.

[0398] 390. The method of aspect 388, wherein said hematologic malignancy is acute myeloid leukemia (AML).

[0399] 391. The method of aspect 325, wherein said cancer is metastatic.Immorta-ANKC-PCT

[0400] 392. The method of aspect 325, wherein said cancer is refractory to prior immunotherapy.

[0401] 393. The method of aspect 325, wherein said method is administered in a neoadjuvant setting.

[0402] 394. The method of aspect 325, wherein said method is administered in an adjuvant setting.

[0403] 395. The method of aspect 325, wherein said combination is formulated in a single pharmaceutical composition.

[0404] 396. The method of aspect 395, wherein said pharmaceutical composition is a tablet.

[0405] 397. The method of aspect 395, wherein said pharmaceutical composition is an injectable solution.

[0406] 398. The method of aspect 325, wherein said method further comprises administering a chemotherapeutic agent.

[0407] 399. The method of aspect 398, wherein said chemotherapeutic agent is selected from the group consisting of cisplatin, doxorubicin, and paclitaxel.

[0408] 400. The method of aspect 325, wherein said method further comprises administering radiation therapy.

[0409] 401. The method of aspect 325, wherein said method is administered to a subject with a biomarker indicative of senescent cell accumulation.

[0410] 402. The method of aspect 401, wherein said biomarker is selected from the group consisting of p16INK4a, p21CIP1, and senescence-associated P-galactosidase (SA-β-gal).

[0411] 403. The method of aspect 325, wherein said method is administered to a subject with a biomarker indicative of NK cell dysfunction.

[0412] 404. The method of aspect 403, wherein said biomarker is selected from the group consisting of reduced CD 16 expression and reduced NKG2D expression.

[0413] 405. The method of aspect 325, wherein said method is administered to a subject with a biomarker indicative of elevated T regulatory cell activity.

[0414] 406. The method of aspect 405, wherein said biomarker is selected from the group consisting of elevated FOXP3 expression and elevated IL-10 levels.

[0415] 407. The method of aspect 325, wherein said agent that stimulates NK cell activity comprises a toll-like receptor (TLR) agonist.

[0416] 408. The method of aspect 407, wherein said TLR agonist is imiquimod.Immorta-ANKC-PCT

[0417] 409. The method of aspect 325, wherein said senolytic agent is a peptide-based senolytic.

[0418] 410. The method of aspect 409, wherein said peptide-based senolytic targets FOXO4.

[0419] 411. The method of aspect 325, wherein said agent that suppresses T regulatory cells comprises a TGF-β inhibitor.

[0420] 412. The method of aspect 411, wherein said TGF-β inhibitor is galunisertib.

[0421] 413. The method of aspect 325, wherein said method enhances NK cell infiltration into the tumor microenvironment.

[0422] 414. The method of aspect 325, wherein said method reduces the immunosuppressive activity of the tumor microenvironment.

[0423] 415. The method of aspect 325, wherein said method increases the ratio of effector NK cells to T regulatory cells in the tumor microenvironment.

[0424] 416. The method of aspect 325, wherein said senolytic agent is administered in a pulsatile dosing regimen.

[0425] 417. The method of aspect 416, wherein said pulsatile dosing regimen comprises administering said senolytic agent for 3 days followed by 11 days without administration.

[0426] 418. The method of aspect 325, wherein said agent that stimulates NK cell activity is administered in a metronomic dosing schedule.

[0427] 419. The method of aspect 325, wherein said agent that suppresses T regulatory cells is administered weekly.

[0428] 420. The method of aspect 325, wherein said senolytic agent is formulated as a nanoparticle.

[0429] 421. The method of aspect 325, wherein said agent that stimulates NK cell activity is conjugated to a targeting moiety.

[0430] 422. The method of aspect 421, wherein said targeting moiety is specific to a tumor-associated antigen.

[0431] 423. The method of aspect 325, wherein said agent that suppresses T regulatory cells is formulated in a liposomal composition.

[0432] 424. The method of aspect 325, wherein said method is administered to a subject with a genetic mutation associated with cancer.

[0433] 425. The method of aspect 424, wherein said genetic mutation is in a gene selected from the group consisting of TP53, KRAS, and PTEN.Immorta-ANKC-PCT

[0434] 426. The method of aspect 325, wherein said method treats a cancer with a high tumor mutational burden.

[0435] 427. The method of aspect 325, wherein said method treats a cancer exhibiting microsatellite instability.

[0436] 428. The method of aspect 325, wherein said agent that stimulates NK cell activity comprises a STING agonist.

[0437] 429. The method of aspect 428, wherein said STING agonist is ADU-S100.

[0438] 430. The method of aspect 325, wherein said senolytic agent is a natural compound.

[0439] 431. The method of aspect 430, wherein said natural compound is luteolin.

[0440] 432. The method of aspect 325, wherein said agent that suppresses T regulatory cells comprises an anti-GITR antibody.

[0441] 433. The method of aspect 432, wherein said anti-GITR antibody is TRX518.

[0442] 434. The method of aspect 325, wherein said method is administered to a pediatric subject.

[0443] 435. The method of aspect 325, wherein said method is administered to an adult subject.

[0444] 436. The method of aspect 325, wherein said method is administered in a first-line treatment setting.

[0445] 437. The method of aspect 325, wherein said method is administered in a second-line treatment setting.

[0446] 438. The method of aspect 325, wherein said method achieves a plasma concentration of said senolytic agent of about 0.1 μM to about 100 μM.

[0447] 439. The method of aspect 325, wherein said method achieves a plasma concentration of said agent that stimulates NK cell activity of about 0.1 pg / mL to about 10 pg / mL.

[0448] 440. The method of aspect 325, wherein said method achieves a reduction in T regulatory cell numbers by at least 20%.

[0449] 441. The method of aspect 325, wherein said method further comprises administering a targeted therapy.

[0450] 442. The method of aspect 441, wherein said targeted therapy is a PARP inhibitor.

[0451] 443. The method of aspect 442, wherein said PARP inhibitor is olaparib.Immorta-ANKC-PCT

[0452] 444. The method of aspect 325, wherein said method further comprises administering an epigenetic modifier.

[0453] 445. The method of aspect 444, wherein said epigenetic modifier is a DNA methyltransferase inhibitor.

[0454] 446. The method of aspect 445, wherein said DNA methyltransferase inhibitor is azacitidine.

[0455] 447. The method of aspect 325, wherein said method is guided by pharmacodynamic monitoring.

[0456] 448. The method of aspect 447, wherein said pharmacodynamic monitoring comprises measuring NK cell CD107a expression.

[0457] 449. The method of aspect 447, wherein said pharmacodynamic monitoring comprises measuring T regulatory cell FOXP3 expression.

[0458] 450. The method of aspect 447, wherein said pharmacodynamic monitoring comprises measuring senescent cell p16^INK4a expression.

[0459] 451. The method of aspect 325, wherein said senolytic agent is administered via inhalation.

[0460] 452. The method of aspect 325, wherein said agent that stimulates NK cell activity is administered via a transdermal patch.

[0461] 453. The method of aspect 325, wherein said agent that suppresses T regulatory cells is administered intratumorally.

[0462] 454. The method of aspect 325, wherein said method treats a cancer with elevated SASP expression.

[0463] 455. The method of aspect 325, wherein said method is administered to a subject with a tumor exhibiting PD-L1 overexpression.

[0464] 456. The method of aspect 325, wherein said method increases progression-free survival by at least 3 months.

[0465] 457. The method of aspect 325, wherein said method increases overall survival by at least 6 months.

[0466] 458. The method of aspect 325, wherein said method reduces tumor volume by at least 20%.

[0467] 459. The method of aspect 325, wherein said method is administered in combination with a metabolic modulator.

[0468] 460. The method of aspect 459, wherein said metabolic modulator is metformin.Immorta-ANKC-PCT

[0469] 461. The method of aspect 325, wherein said method treats a sarcoma.

[0470] 462. The method of aspect 325, wherein said method treats a glioblastoma.

[0471] 463. The method of aspect 325, wherein said senolytic agent is a synthetic analog of a naturally occurring senolytic.

[0472] 464. The method of aspect 463, wherein said naturally occurring senolytic is quercetin.

[0473] 465. The method of aspect 325, wherein said agent that stimulates NK cell activity comprises a monoclonal antibody.

[0474] 466. The method of aspect 465, wherein said monoclonal antibody targets CD137.

[0475] 467. The method of aspect 466, wherein said monoclonal antibody is urelumab.

[0476] 468. The method of aspect 325, wherein said agent that suppresses T regulatory cells comprises an anti-OX40 antibody.

[0477] 469. The method of aspect 468, wherein said anti-OX40 antibody is PF- 04518600.

[0478] 470. The method of aspect 325, wherein said method is administered in a regimen that includes periodic imaging to monitor tumor response.

[0479] 471. The method of aspect 470, wherein said imaging is selected from the group consisting of MRI, CT, and PET scans.

[0480] 472. The method of aspect 325, wherein said method is administered to a subject with a history of chemotherapy resistance.

[0481] 473. The method of aspect 325, wherein said method enhances the expression of NK cell-activating receptors.

[0482] 474. The method of aspect 473, wherein said NK cell -activating receptors are selected from the group consisting of NKp30, NKp44, and NKp46.

[0483] 475. The method of aspect 325, wherein said method reduces the expression of NK cell-inhibitory receptors.

[0484] 476. The method of aspect 475, wherein said NK cell -inhibitory receptors are selected from the group consisting of KIR2DL and NKG2A.

[0485] 477. The method of aspect 325, wherein said method is administered in a sustained-release formulation.

[0486] 478. The method of aspect 325, wherein said method is administered in an immediate-release formulation.Immorta-ANKC-PCT

[0487] 479. The method of aspect 325, wherein said method treats a cancer with a BRAF mutation.

[0488] 480. The method of aspect 325, wherein said method treats a cancer with an ALK rearrangement.

[0489] 481. The method of aspect 325, wherein said method is administered to a subject with elevated circulating senescent cells.

[0490] 482. The method of aspect 325, wherein said method is administered to a subject with elevated tumor-infiltrating T regulatory cells.

[0491] 483. The method of aspect 325, wherein said method increases NK cell granzyme B release.

[0492] 484. The method of aspect 325, wherein said method increases NK cell perforin release.

[0493] 485. The method of aspect 325, wherein said method reduces tumor hypoxia.

[0494] 486. The method of aspect 325, wherein said method is administered in combination with an anti -angiogenic agent.

[0495] 487. The method of aspect 486, wherein said anti-angiogenic agent is bevacizumab.

[0496] 488. The method of aspect 325, wherein said method is administered to a subject with a tumor exhibiting high IL-6 expression.

[0497] 489. The method of aspect 325, wherein said method is administered to a subject with a tumor exhibiting high IL-8 expression.

[0498] 490. The method of aspect 325, wherein said agent that stimulates NK cell activity comprises a cancer vaccine.

[0499] 491. The method of aspect 490, wherein said cancer vaccine is a neoantigen vaccine.

[0500] 492. The method of aspect 325, wherein said senolytic agent comprises an mTOR inhibitor.

[0501] 493. The method of aspect 492, wherein said mTOR inhibitor is rapamycin.

[0502] 494. The method of aspect 325, wherein said agent that suppresses T regulatory cells comprises a CCR4 antagonist.

[0503] 495. The method of aspect 494, wherein said CCR4 antagonist is mogamulizumab.

[0504] 496. The method of aspect 325, wherein said method is administered in a dose-escalation protocol.Immorta-ANKC-PCT

[0505] 497. The method of aspect 325, wherein said method is administered to a subject with a tumor exhibiting CD47 overexpression.

[0506] 498. The method of aspect 325, wherein said method reduces tumor fibrosis.

[0507] 499. The method of aspect 325, wherein said method is administered in a regimen that minimizes immune-related adverse events.

[0508] 500. The method of aspect 325, wherein said method is administered to a subject with a rare cancer.

[0509] 501. The method of aspect 500, wherein said rare cancer is cholangiocarcinoma.

[0510] 502. The method of aspect 325, wherein said method enhances NK cell proliferation.

[0511] 503. The method of aspect 325, wherein said method reduces T regulatory cell proliferation.

[0512] 504. The method of aspect 325, wherein said method is administered in a regimen guided by liquid biopsy.

[0513] 505. The method of aspect 504, wherein said liquid biopsy measures circulating tumor DNA.

[0514] 506. The method of aspect 325, wherein said method treats a cancer with a HER2 amplification.

[0515] 507. The method of aspect 325, wherein said method treats a cancer with an EGFR mutation.

[0516] 508. The method of aspect 325, wherein said method is administered to a subject with a tumor exhibiting high VEGF expression.

[0517] 509. The method of aspect 325, wherein said method is administered in a combination with a proteasome inhibitor.

[0518] 510. The method of aspect 509, wherein said proteasome inhibitor is bortezomib.

[0519] 511. The method of aspect 325, wherein said method is administered to a subject with a tumor exhibiting high TGF-β expression.

[0520] 512. The method of aspect 325, wherein said method reduces tumor-infiltrating myeloid-derived suppressor cells.

[0521] 513. The method of aspect 325, wherein said method is administered in a regimen that includes supportive care to manage side effects.Immorta-ANKC-PCT

[0522] 514. The method of aspect 325, wherein said agent that stimulates NK cell activity comprises an oncolytic virus.

[0523] 515. The method of aspect 514, wherein said oncolytic virus is talimogene laherparepvec.

[0524] 516. The method of aspect 325, wherein said senolytic agent comprises a galectin-3 inhibitor.

[0525] 517. The method of aspect 516, wherein said galectin-3 inhibitor is GCS- 100.

[0526] 518. The method of aspect 325, wherein said agent that suppresses T regulatory cells comprises an anti-CD39 antibody.

[0527] 519. The method of aspect 325, wherein said method is administered to a subject with a tumor exhibiting high PD-1 expression.

[0528] 520. The method of aspect 325, wherein said method increases the expression of MHC class I molecules on tumor cells.

[0529] 521. The method of aspect 325, wherein said method reduces tumor immune evasion.

[0530] 522. The method of aspect 325, wherein said method is administered in a regimen that achieves a complete response in at least 10% of subjects.

[0531] 523. The method of aspect 325, wherein said method is administered in a regimen that achieves a partial response in at least 30% of subjects.

[0532] 524. The method of aspect 325, wherein said method is administered to a subject with a tumor exhibiting a senescence-associated secretory phenotype (SASP).

[0533] 525. A method of treating cancer in a subject in need thereof, the method comprising:administering to the subject a therapeutically effective amount of a senolytic agent; and administering to the subject a therapeutically effective amount of a naturally occurring compound that activates NK cell tumor-killing ability,wherein the combination of the senolytic agent and the naturally occurring compound reduces cancer cell burden in the subject.

[0534] 526. The method of aspect 525, wherein the senolytic agent selectively induces apoptosis in senescent cancer cells.

[0535] 527. The method of aspect 525, wherein the senolytic agent is selected from the group consisting of dasatinib, quercetin, navitoclax, and fisetin.

[0536] 528. The method of aspect 527, wherein the senolytic agent is dasatinib.Immorta-ANKC-PCT

[0537] 529. The method of aspect 527, wherein the senolytic agent is quercetin.

[0538] 530. The method of aspect 527, wherein the senolytic agent is navitoclax.

[0539] 531. The method of aspect 527, wherein the senolytic agent is fisetin.

[0540] 532. The method of aspect 525, wherein the naturally occurring compound is a plant-derived compound.

[0541] 533. The method of aspect 532, wherein the plant-derived compound is a polysaccharide.

[0542] 534. The method of aspect 533, wherein the polysaccharide is selected from the group consisting of beta-glucans, arabinogalactans, and fucoidans.

[0543] 535. The method of aspect 534, wherein the polysaccharide is a beta-glucan derived from a source selected from the group consisting of mushrooms, yeast, and oats.

[0544] 536. The method of aspect 535, wherein the beta-glucan is derived from a mushroom selected from the group consisting of reishi, shiitake, and maitake.

[0545] 537. The method of aspect 534, wherein the polysaccharide is an arabinogalactan derived from larch tree.

[0546] 538. The method of aspect 534, wherein the polysaccharide is a fucoidan derived from brown seaweed.

[0547] 539. The method of aspect 532, wherein the plant-derived compound is a polyphenol.

[0548] 540. The method of aspect 539, wherein the polyphenol is selected from the group consisting of curcumin, resveratrol, and epigallocatechin gallate (EGCG).

[0549] 541. The method of aspect 540, wherein the polyphenol is curcumin.

[0550] 542. The method of aspect 540, wherein the polyphenol is resveratrol.

[0551] 543. The method of aspect 540, wherein the polyphenol is epigallocatechin gallate (EGCG).

[0552] 544. The method of aspect 525, wherein the naturally occurring compound is a microbial-derived compound.

[0553] 545. The method of aspect 544, wherein the microbial-derived compound is a lipopeptide.

[0554] 546. The method of aspect 545, wherein the lipopeptide is selected from the group consisting of surfactin and iturin.

[0555] 547. The method of aspect 525, wherein the naturally occurring compound enhances NK cell activity by upregulating expression of activating receptors on NK cells.Immorta-ANKC-PCT

[0556] 548. The method of aspect 547, wherein the activating receptors include at least one of NKG2D, NKp46, and NKp30.

[0557] 549. The method of aspect 525, wherein the naturally occurring compound increases NK cell cytotoxicity against cancer cells by at least 10% compared to NK cells not exposed to the compound.

[0558] 550. The method of aspect 525, wherein the cancer is a solid tumor.

[0559] 551. The method of aspect 550, wherein the solid tumor is selected from the group consisting of breast cancer, lung cancer, pancreatic cancer, colorectal cancer, and melanoma.

[0560] 552. The method of aspect 551, wherein the solid tumor is breast cancer.

[0561] 553. The method of aspect 551, wherein the solid tumor is lung cancer.

[0562] 554. The method of aspect 551, wherein the solid tumor is pancreatic cancer.

[0563] 555. The method of aspect 551, wherein the solid tumor is colorectal cancer.

[0564] 556. The method of aspect 551, wherein the solid tumor is melanoma.

[0565] 557. The method of aspect 525, wherein the cancer is a hematologic malignancy.

[0566] 558. The method of aspect 557, wherein the hematologic malignancy is selected from the group consisting of leukemia, lymphoma, and multiple myeloma.

[0567] 559. The method of aspect 558, wherein the hematologic malignancy is leukemia.

[0568] 560. The method of aspect 558, wherein the hematologic malignancy is lymphoma.

[0569] 561. The method of aspect 558, wherein the hematologic malignancy is multiple myeloma.

[0570] 562. The method of aspect 525, wherein the senolytic agent and the naturally occurring compound are administered simultaneously.

[0571] 563. The method of aspect 525, wherein the senolytic agent and the naturally occurring compound are administered sequentially.

[0572] 564. The method of aspect 563, wherein the senolytic agent is administered prior to the naturally occurring compound.

[0573] 565. The method of aspect 563, wherein the naturally occurring compound is administered prior to the senolytic agent.

[0574] 566. The method of aspect 525, wherein the senolytic agent is administered at a dose ranging from 0.1 mg / kg to 100 mg / kg of the subject’s body weight.Immorta-ANKC-PCT

[0575] 567. The method of aspect 525, wherein the naturally occurring compound is administered at a dose ranging from 1 mg / kg to 500 mg / kg of the subject’s body weight.

[0576] 568. The method of aspect 525, wherein the senolytic agent is administered orally.

[0577] 569. The method of aspect 525, wherein the senolytic agent is administered intravenously.

[0578] 570. The method of aspect 525, wherein the naturally occurring compound is administered orally.

[0579] 571. The method of aspect 525, wherein the naturally occurring compound is administered intravenously.

[0580] 572. The method of aspect 525, wherein the senolytic agent and the naturally occurring compound are administered as part of a single pharmaceutical composition.

[0581] 573. The method of aspect 572, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier.

[0582] 574. The method of aspect 525, wherein the senolytic agent and the naturally occurring compound are administered as separate pharmaceutical compositions.

[0583] 575. The method of aspect 525, wherein the administration occurs daily for a period of at least one week.

[0584] 576. The method of aspect 525, wherein the administration occurs weekly for a period of at least one month.

[0585] 577. The method of aspect 525, wherein the subject is a human.

[0586] 578. The method of aspect 525, wherein the subject is a non-human mammal.

[0587] 579. The method of aspect 525, further comprising administering an additional therapeutic agent.

[0588] 580. The method of aspect 579, wherein the additional therapeutic agent is an immune checkpoint inhibitor.

[0589] 581. The method of aspect 580, wherein the immune checkpoint inhibitor targets at least one of PD-1, PD-L1, or CTLA-4.

[0590] 582. The method of aspect 581, wherein the immune checkpoint inhibitor is selected from the group consisting of pembrolizumab, nivolumab, and ipilimumab.

[0591] 583. The method of aspect 579, wherein the additional therapeutic agent is a chemotherapeutic agent.Immorta-ANKC-PCT

[0592] 584. The method of aspect 583, wherein the chemotherapeutic agent is selected from the group consisting of paclitaxel, doxorubicin, and cisplatin.

[0593] 585. The method of aspect 525, further comprising monitoring the subject for a reduction in tumor size.

[0594] 586. The method of aspect 525, further comprising monitoring the subject for an increase in NK cell activity.

[0595] 587. The method of aspect 525, wherein the combination of the senolytic agent and the naturally occurring compound results in a synergistic effect on cancer cell reduction.

[0596] 588. The method of aspect 525, wherein the method increases the subject’s progression-free survival by at least 10% compared to treatment with the senolytic agent alone.

[0597] 589. The method of aspect 525, wherein the method increases the subject’s overall survival by at least 10% compared to treatment with the naturally occurring compound alone.

[0598] 590. The method of aspect 525, wherein the cancer is metastatic.

[0599] 591. The method of aspect 525, wherein the cancer is refractory to at least one prior therapy.

[0600] 592. The method of aspect 525, wherein the senolytic agent targets at least one pathway selected from the group consisting of Bcl-2, PI3K / AKT, and p53.

[0601] 593. The method of aspect 525, wherein the naturally occurring compound increases the expression of at least one cytokine selected from the group consisting of IFN-γ and TNF-a in NK cells.

[0602] 594. The method of aspect 525, wherein the method reduces the number of senescent cells in the tumor microenvironment by at least 20%.

[0603] 595. The method of aspect 525, wherein the method increases NK cell infiltration into the tumor by at least 15%.

[0604] 596. The method of aspect 525, wherein the naturally occurring compound is administered in a liposomal formulation.

[0605] 597. The method of aspect 525, wherein the senolytic agent is administered in a nanoparticle formulation.

[0606] 598. The method of aspect 525, wherein the method further comprises a step of identifying the subject as having a cancer with high senescent cell burden prior to administration.Immorta-ANKC-PCT

[0607] 599. The method of aspect 598, wherein the senescent cell burden is determined by measuring the expression of at least one senescence marker selected from the group consisting of p16, p21, and SA-β-gal.

[0608] 600. The method of aspect 525, wherein the method further comprises a step of identifying the subject as having low NK cell activity prior to administration.

[0609] 601. The method of aspect 600, wherein the NK cell activity is determined by measuring the expression of at least one NK cell activation marker selected from the group consisting of CD69 and CD107a.

[0610] 602. The method of aspect 525, wherein the naturally occurring compound is extracted using a solvent selected from the group consisting of water, ethanol, and methanol.

[0611] 603. The method of aspect 525, wherein the naturally occurring compound has a purity of at least 90%.

[0612] 604. The method of aspect 525, wherein the senolytic agent and the naturally occurring compound are administered in a ratio ranging from 1: 10 to 10: 1 by weight.

[0613] 605. The method of aspect 525, wherein the method further comprises administering a dietary supplement to the subject.

[0614] 606. The method of aspect 605, wherein the dietary supplement comprises at least one vitamin selected from the group consisting of vitamin C and vitamin D.

[0615] 607. The method of aspect 525, wherein the method further comprises subjecting the subject to radiation therapy.

[0616] 608. The method of aspect 525, wherein the method further comprises surgically resecting a tumor from the subject prior to administration.

[0617] 609. The method of aspect 525, wherein the method is used as an adjuvant therapy following a primary cancer treatment.

[0618] 610. The method of aspect 525, wherein the method is used as a neoadjuvant therapy prior to a primary cancer treatment.

[0619] 611. The method of aspect 525, wherein the method reduces cancer recurrence rates by at least 10% compared to a control group not receiving the combination.

[0620] 612. The method of aspect 525, wherein the method is performed in combination with a ketogenic diet.

[0621] 613. The method of aspect 525, wherein the naturally occurring compound is administered via a transdermal patch.Immorta-ANKC-PCT

[0622] 614. The method of aspect 525, wherein the senolytic agent is administered via inhalation.

[0623] 615. The method of aspect 525, wherein the method further comprises monitoring the subject for adverse effects.

[0624] 616. The method of aspect 615, wherein the adverse effects include at least one of hepatotoxicity, nephrotoxicity, and gastrointestinal distress.

[0625] 617. The method of aspect 525, wherein the method is performed in a subject with a genetic mutation associated with cancer.

[0626] 618. The method of aspect 617, wherein the genetic mutation is in a gene selected from the group consisting of BRCA1, BRCA2, and TP53.

[0627] 619. The method of aspect 525, wherein the method further comprises administering an NK cell-enhancing cytokine.

[0628] 620. The method of aspect 619, wherein the NK cell-enhancing cytokine is selected from the group consisting of IL-2, IL-15, and IL-21.

[0629] 621. The method of aspect 525, wherein the naturally occurring compound is administered in a sustained-release formulation.

[0630] 622. The method of aspect 525, wherein the senolytic agent is administered in an immediate-release formulation.

[0631] 623. The method of aspect 525, wherein the method reduces tumor-associated inflammation by at least 10%.

[0632] 624. The method of aspect 525, wherein the method increases the subject’s quality of life as measured by a standardized quality-of-life index.

[0633] 625. A method of treating cancer comprising administration of a microbiome metabolite together with a senolytic.

[0634] 625. A method of treating cancer in a subject in need thereof, the method comprising:administering to the subject a therapeutically effective amount of a senolytic agent; and administering to the subject a therapeutically effective amount of a microbiome metabolite, wherein the combination of the senolytic agent and the microbiome metabolite reduces cancer cell burden in the subject.

[0635] 626. The method of aspect 625, wherein the senolytic agent selectively induces apoptosis in senescent cancer cells.

[0636] 627. The method of aspect 625, wherein the senolytic agent is selected from the group consisting of dasatinib, quercetin, navitoclax, and fisetin.Immorta-ANKC-PCT

[0637] 628. The method of aspect 627, wherein the senolytic agent is dasatinib.

[0638] 629. The method of aspect 627, wherein the senolytic agent is quercetin.

[0639] 630. The method of aspect 627, wherein the senolytic agent is navitoclax.

[0640] 631. The method of aspect 627, wherein the senolytic agent is fisetin.

[0641] 632. The method of aspect 625, wherein the microbiome metabolite is a short-chain fatty acid.

[0642] 633. The method of aspect 632, wherein the short-chain fatty acid is selected from the group consisting of butyrate, propionate, and acetate.

[0643] 634. The method of aspect 633, wherein the short-chain fatty acid is butyrate.

[0644] 635. The method of aspect 633, wherein the short-chain fatty acid is propionate.

[0645] 636. The method of aspect 633, wherein the short-chain fatty acid is acetate.

[0646] 637. The method of aspect 625, wherein the microbiome metabolite is a secondary bile acid.

[0647] 638. The method of aspect 637, wherein the secondary bile acid is selected from the group consisting of deoxycholic acid and lithocholic acid.

[0648] 639. The method of aspect 638, wherein the secondary bile acid is deoxycholic acid.

[0649] 640. The method of aspect 638, wherein the secondary bile acid is lithocholic acid.

[0650] 641. The method of aspect 625, wherein the microbiome metabolite is a tryptophan metabolite.

[0651] 642. The method of aspect 641, wherein the tryptophan metabolite is selected from the group consisting of indole-3 -acetic acid, indole-3 -propionic acid, and kynurenine.

[0652] 643. The method of aspect 642, wherein the tryptophan metabolite is indole- 3 -acetic acid.

[0653] 644. The method of aspect 642, wherein the tryptophan metabolite is indole- 3 -propionic acid.

[0654] 645. The method of aspect 642, wherein the tryptophan metabolite is kynurenine.

[0655] 646. The method of aspect 625, wherein the microbiome metabolite is derived from gut microbiota.Immorta-ANKC-PCT

[0656] 647. The method of aspect 646, wherein the gut microbiota comprises at least one bacterial genus selected from the group consisting of Lactobacillus, Bifidobacterium, and Clostridium.

[0657] 648. The method of aspect 625, wherein the microbiome metabolite enhances immune cell activity against cancer cells.

[0658] 649. The method of aspect 648, wherein the immune cell activity is mediated by at least one of T cells, NK cells, or macrophages.

[0659] 650. The method of aspect 649, wherein the immune cell activity is mediated by NK cells.

[0660] 651. The method of aspect 625, wherein the cancer is a solid tumor.

[0661] 652. The method of aspect 651, wherein the solid tumor is selected from the group consisting of breast cancer, lung cancer, pancreatic cancer, colorectal cancer, and melanoma.

[0662] 653. The method of aspect 652, wherein the solid tumor is breast cancer.

[0663] 654. The method of aspect 652, wherein the solid tumor is lung cancer.

[0664] 655. The method of aspect 652, wherein the solid tumor is pancreatic cancer.

[0665] 656. The method of aspect 652, wherein the solid tumor is colorectal cancer.

[0666] 657. The method of aspect 652, wherein the solid tumor is melanoma.

[0667] 658. The method of aspect 625, wherein the cancer is a hematologic malignancy.

[0668] 659. The method of aspect 658, wherein the hematologic malignancy is selected from the group consisting of leukemia, lymphoma, and multiple myeloma.

[0669] 660. The method of aspect 659, wherein the hematologic malignancy is leukemia.

[0670] 661. The method of aspect 659, wherein the hematologic malignancy is lymphoma.

[0671] 662. The method of aspect 659, wherein the hematologic malignancy is multiple myeloma.

[0672] 663. The method of aspect 625, wherein the senolytic agent and the microbiome metabolite are administered simultaneously.

[0673] 664. The method of aspect 625, wherein the senolytic agent and the microbiome metabolite are administered sequentially.

[0674] 665. The method of aspect 664, wherein the senolytic agent is administered prior to the microbiome metabolite.Immorta-ANKC-PCT

[0675] 666. The method of aspect 664, wherein the microbiome metabolite is administered prior to the senolytic agent.

[0676] 667. The method of aspect 625, wherein the senolytic agent is administered at a dose ranging from 0.1 mg / kg to 100 mg / kg of the subject’s body weight.

[0677] 668. The method of aspect 625, wherein the microbiome metabolite is administered at a dose ranging from 0.5 mg / kg to 200 mg / kg of the subject’s body weight.

[0678] 669. The method of aspect 625, wherein the senolytic agent is administered orally.

[0679] 670. The method of aspect 625, wherein the senolytic agent is administered intravenously.

[0680] 671. The method of aspect 625, wherein the microbiome metabolite is administered orally.

[0681] 672. The method of aspect 625, wherein the microbiome metabolite is administered rectally.

[0682] 673. The method of aspect 625, wherein the senolytic agent and the microbiome metabolite are administered as part of a single pharmaceutical composition.

[0683] 674. The method of aspect 673, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier.

[0684] 675. The method of aspect 625, wherein the senolytic agent and the microbiome metabolite are administered as separate pharmaceutical compositions.

[0685] 676. The method of aspect 625, wherein the administration occurs daily for a period of at least one week.

[0686] 677. The method of aspect 625, wherein the administration occurs weekly for a period of at least one month.

[0687] 678. The method of aspect 625, wherein the subject is a human.

[0688] 679. The method of aspect 625, wherein the subject is a non-human mammal.

[0689] 680. The method of aspect 625, further comprising administering an additional therapeutic agent.

[0690] 681. The method of aspect 680, wherein the additional therapeutic agent is an immune checkpoint inhibitor.

[0691] 682. The method of aspect 681, wherein the immune checkpoint inhibitor targets at least one of PD-1, PD-L1, or CTLA-4.Immorta-ANKC-PCT

[0692] 683. The method of aspect 682, wherein the immune checkpoint inhibitor is selected from the group consisting of pembrolizumab, nivolumab, and ipilimumab.

[0693] 684. The method of aspect 680, wherein the additional therapeutic agent is a chemotherapeutic agent.

[0694] 685. The method of aspect 684, wherein the chemotherapeutic agent is selected from the group consisting of paclitaxel, doxorubicin, and cisplatin.

[0695] 686. The method of aspect 625, further comprising monitoring the subject for a reduction in tumor size.

[0696] 687. The method of aspect 625, further comprising monitoring the subject for changes in gut microbiota composition.

[0697] 688. The method of aspect 625, wherein the combination of the senolytic agent and the microbiome metabolite results in a synergistic effect on cancer cell reduction.

[0698] 689. The method of aspect 625, wherein the method increases the subject’s progression-free survival by at least 10% compared to treatment with the senolytic agent alone.

[0699] 690. The method of aspect 625, wherein the method increases the subject’s overall survival by at least 10% compared to treatment with the microbiome metabolite alone.

[0700] 691. The method of aspect 625, wherein the cancer is metastatic.

[0701] 692. The method of aspect 625, wherein the cancer is refractory to at least one prior therapy.

[0702] 693. The method of aspect 625, wherein the senolytic agent targets at least one pathway selected from the group consisting of Bcl-2, PI3K / AKT, and p53.

[0703] 694. The method of aspect 625, wherein the microbiome metabolite modulates at least one immune pathway selected from the group consisting of the aryl hydrocarbon receptor (AhR) pathway and the G-protein-coupled receptor (GPCR) pathway.

[0704] 695. The method of aspect 625, wherein the method reduces the number of senescent cells in the tumor microenvironment by at least 20%.

[0705] 696. The method of aspect 625, wherein the method increases immune cell infiltration into the tumor by at least 15%.

[0706] 697. The method of aspect 625, wherein the microbiome metabolite is administered in an encapsulated formulation.Immorta-ANKC-PCT

[0707] 698. The method of aspect 625, wherein the senolytic agent is administered in a nanoparticle formulation.

[0708] 699. The method of aspect 625, wherein the method further comprises a step of identifying the subject as having a dysbiotic gut microbiome prior to administration.

[0709] 700. The method of aspect 699, wherein the dysbiotic gut microbiome is characterized by a reduction in at least one bacterial genus selected from the group consisting of Lactobacillus and Bifidobacterium.

[0710] 701. The method of aspect 625, wherein the method further comprises a step of identifying the subject as having a cancer with high senescent cell burden prior to administration.

[0711] 702. The method of aspect 701, wherein the senescent cell burden is determined by measuring the expression of at least one senescence marker selected from the group consisting of p16, p21, and SA-β-gal.

[0712] 703. The method of aspect 625, wherein the microbiome metabolite is produced by fermentation of dietary fiber by gut microbiota.

[0713] 704. The method of aspect 625, wherein the microbiome metabolite has a purity of at least 95%.

[0714] 705. The method of aspect 625, wherein the senolytic agent and the microbiome metabolite are administered in a ratio ranging from 1:5 to 5:1 by weight.

[0715] 706. The method of aspect 625, wherein the method further comprises administering a probiotic to the subject.

[0716] 707. The method of aspect 706, wherein the probiotic comprises at least one strain selected from the group consisting of Lactobacillus acidophilus and Bifidobacterium longum.

[0717] 708. The method of aspect 625, wherein the method further comprises administering a prebiotic to the subject.

[0718] 709. The method of aspect 708, wherein the prebiotic is selected from the group consisting of inulin, fructooligosaccharides (FOS), and galactooligosaccharides (GOS).

[0719] 710. The method of aspect 625, wherein the method further comprises subjecting the subject to radiation therapy.

[0720] 711. The method of aspect 625, wherein the method further comprises surgically resecting a tumor from the subject prior to administration.Immorta-ANKC-PCT

[0721] 712. The method of aspect 625, wherein the method is used as an adjuvant therapy following a primary cancer treatment.

[0722] 713. The method of aspect 625, wherein the method is used as a neoadjuvant therapy prior to a primary cancer treatment.

[0723] 714. The method of aspect 625, wherein the method reduces cancer recurrence rates by at least 10% compared to a control group not receiving the combination.

[0724] 715. The method of aspect 625, wherein the method is performed in combination with a high-fiber diet.

[0725] 716. The method of aspect 625, wherein the microbiome metabolite is administered via a colonic delivery system.

[0726] 717. The method of aspect 625, wherein the senolytic agent is administered via inhalation.

[0727] 718. The method of aspect 625, wherein the method further comprises monitoring the subject for adverse effects.

[0728] 719. The method of aspect 718, wherein the adverse effects include at least one of gastrointestinal distress, hepatotoxicity, and nephrotoxicity.

[0729] 720. The method of aspect 625, wherein the method is performed in a subject with a genetic mutation associated with cancer.

[0730] 721. The method of aspect 720, wherein the genetic mutation is in a gene selected from the group consisting of BRCA1, BRCA2, and TP53.

[0731] 722. The method of aspect 625, wherein the microbiome metabolite is administered in a sustained-release formulation.

[0732] 723. The method of aspect 625, wherein the senolytic agent is administered in an immediate-release formulation.

[0733] 724. The method of aspect 625, wherein the method reduces tumor-associated inflammation by at least 10%.

[0734] 725. A method of treating cancer in a subject in need thereof, the method comprising:administering to the subject a therapeutically effective amount of a senolytic agent; and administering to the subject a therapeutically effective amount of an agent or combination of agents capable of reducing T regulatory cell number and / or T regulatory cell activity, wherein the combination of the senolytic agent and the agent or combination of agents reduces cancer cell burden in the subject.Immorta-ANKC-PCT

[0735] 726. The method of aspect 725, wherein the senolytic agent selectively induces apoptosis in senescent cancer cells.

[0736] 727. The method of aspect 725, wherein the senolytic agent is selected from the group consisting of dasatinib, quercetin, navitoclax, and fisetin.

[0737] 728. The method of aspect 727, wherein the senolytic agent is dasatinib.

[0738] 729. The method of aspect 727, wherein the senolytic agent is quercetin.

[0739] 730. The method of aspect 727, wherein the senolytic agent is navitoclax.

[0740] 731. The method of aspect 727, wherein the senolytic agent is fisetin.

[0741] 732. The method of aspect 725, wherein the agent capable of reducing T regulatory cell number and / or T regulatory cell activity is a small molecule.

[0742] 733. The method of aspect 732, wherein the small molecule is selected from the group consisting of cyclophosphamide, imatinib, and sunitinib.

[0743] 734. The method of aspect 733, wherein the small molecule is cyclophosphamide.

[0744] 735. The method of aspect 733, wherein the small molecule is imatinib.

[0745] 736. The method of aspect 733, wherein the small molecule is sunitinib.

[0746] 737. The method of aspect 725, wherein the agent capable of reducing T regulatory cell number and / or T regulatory cell activity is a monoclonal antibody.

[0747] 738. The method of aspect 737, wherein the monoclonal antibody targets at least one marker on T regulatory cells selected from the group consisting of CTLA-4, CD25, and PD-1.

[0748] 739. The method of aspect 738, wherein the monoclonal antibody is selected from the group consisting of ipilimumab, daclizumab, and pembrolizumab.

[0749] 740. The method of aspect 739, wherein the monoclonal antibody is ipilimumab.

[0750] 741. The method of aspect 739, wherein the monoclonal antibody is daclizumab.

[0751] 742. The method of aspect 739, wherein the monoclonal antibody is pembrolizumab.

[0752] 743. The method of aspect 725, wherein the agent capable of reducing T regulatory cell number and / or T regulatory cell activity is a cytokine.

[0753] 744. The method of aspect 743, wherein the cytokine is selected from the group consisting of IL-2, IL-15, and IL-21.Immorta-ANKC-PCT

[0754] 745. The method of aspect 744, wherein the cytokine is IL-2.

[0755] 746. The method of aspect 744, wherein the cytokine is IL-15.

[0756] 747. The method of aspect 744, wherein the cytokine is IL-21.

[0757] 748. The method of aspect 725, wherein the combination of agents capable of reducing T regulatory cell number and / or T regulatory cell activity comprises a small molecule and a monoclonal antibody.

[0758] 749. The method of aspect 748, wherein the small molecule is cyclophosphamide and the monoclonal antibody is ipilimumab.

[0759] 750. The method of aspect 725, wherein the agent or combination of agents reduces T regulatory cell number by at least 10% in the tumor microenvironment.

[0760] 751. The method of aspect 725, wherein the agent or combination of agents reduces T regulatory cell activity by at least 15% in the tumor microenvironment.

[0761] 752. The method of aspect 725, wherein the agent or combination of agents downregulates the expression of at least one T regulatory cell marker selected from the group consisting of FoxP3, CD25, and CTLA-4.

[0762] 753. The method of aspect 725, wherein the cancer is a solid tumor.

[0763] 754. The method of aspect 753, wherein the solid tumor is selected from the group consisting of breast cancer, lung cancer, pancreatic cancer, colorectal cancer, and melanoma.

[0764] 755. The method of aspect 754, wherein the solid tumor is breast cancer.

[0765] 756. The method of aspect 754, wherein the solid tumor is lung cancer.

[0766] 757. The method of aspect 754, wherein the solid tumor is pancreatic cancer.

[0767] 758. The method of aspect 754, wherein the solid tumor is colorectal cancer.

[0768] 759. The method of aspect 754, wherein the solid tumor is melanoma.

[0769] 760. The method of aspect 725, wherein the cancer is a hematologic malignancy.

[0770] 761. The method of aspect 760, wherein the hematologic malignancy is selected from the group consisting of leukemia, lymphoma, and multiple myeloma.

[0771] 762. The method of aspect 761, wherein the hematologic malignancy is leukemia.

[0772] 763. The method of aspect 761, wherein the hematologic malignancy is lymphoma.

[0773] 764. The method of aspect 761, wherein the hematologic malignancy is multiple myeloma.Immorta-ANKC-PCT

[0774] 765. The method of aspect 725, wherein the senolytic agent and the agent or combination of agents are administered simultaneously.

[0775] 766. The method of aspect 725, wherein the senolytic agent and the agent or combination of agents are administered sequentially.

[0776] 767. The method of aspect 766, wherein the senolytic agent is administered prior to the agent or combination of agents.

[0777] 768. The method of aspect 766, wherein the agent or combination of agents is administered prior to the senolytic agent.

[0778] 769. The method of aspect 725, wherein the senolytic agent is administered at a dose ranging from 0.1 mg / kg to 100 mg / kg of the subject’s body weight.

[0779] 770. The method of aspect 725, wherein the agent or combination of agents is administered at a dose ranging from 0.01 mg / kg to 50 mg / kg of the subject’s body weight.

[0780] 771. The method of aspect 725, wherein the senolytic agent is administered orally.

[0781] 772. The method of aspect 725, wherein the senolytic agent is administered intravenously.

[0782] 773. The method of aspect 725, wherein the agent or combination of agents is administered intravenously.

[0783] 774. The method of aspect 725, wherein the agent or combination of agents is administered subcutaneously.

[0784] 775. The method of aspect 725, wherein the senolytic agent and the agent or combination of agents are administered as part of a single pharmaceutical composition.

[0785] 776. The method of aspect 775, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier.

[0786] 777. The method of aspect 725, wherein the senolytic agent and the agent or combination of agents are administered as separate pharmaceutical compositions.

[0787] 778. The method of aspect 725, wherein the administration occurs daily for a period of at least one week.

[0788] 779. The method of aspect 725, wherein the administration occurs weekly for a period of at least one month.

[0789] 780. The method of aspect 725, wherein the subject is a human.

[0790] 781. The method of aspect 725, wherein the subject is a non-human mammal.Immorta-ANKC-PCT

[0791] 782. The method of aspect 725, further comprising administering an additional therapeutic agent.

[0792] 783. The method of aspect 782, wherein the additional therapeutic agent is an immune checkpoint inhibitor.

[0793] 784. The method of aspect 783, wherein the immune checkpoint inhibitor targets at least one of PD-1, PD-L1, or CTLA-4.

[0794] 785. The method of aspect 784, wherein the immune checkpoint inhibitor is selected from the group consisting of pembrolizumab, nivolumab, and ipilimumab.

[0795] 786. The method of aspect 782, wherein the additional therapeutic agent is a chemotherapeutic agent.

[0796] 787. The method of aspect 786, wherein the chemotherapeutic agent is selected from the group consisting of paclitaxel, doxorubicin, and cisplatin.

[0797] 788. The method of aspect 725, further comprising monitoring the subject for a reduction in tumor size.

[0798] 789. The method of aspect 725, further comprising monitoring the subject for a reduction in T regulatory cell number in the tumor microenvironment.

[0799] 790. The method of aspect 725, further comprising monitoring the subject for a reduction in T regulatory cell activity in the tumor microenvironment.

[0800] 791. The method of aspect 725, wherein the combination of the senolytic agent and the agent or combination of agents results in a synergistic effect on cancer cell reduction.

[0801] 792. The method of aspect 725, wherein the method increases the subject’s progression-free survival by at least 10% compared to treatment with the senolytic agent alone.

[0802] 793. The method of aspect 725, wherein the method increases the subject’s overall survival by at least 10% compared to treatment with the agent or combination of agents alone.

[0803] 794. The method of aspect 725, wherein the cancer is metastatic.

[0804] 795. The method of aspect 725, wherein the cancer is refractory to at least one prior therapy.

[0805] 796. The method of aspect 725, wherein the senolytic agent targets at least one pathway selected from the group consisting of Bcl-2, PI3K / AKT, and p53.Immorta-ANKC-PCT

[0806] 797. The method of aspect 725, wherein the agent or combination of agents inhibits at least one signaling pathway selected from the group consisting of TGF-P, IL-10, and STAT3.

[0807] 798. The method of aspect 725, wherein the method reduces the number of senescent cells in the tumor microenvironment by at least 20%.

[0808] 799. The method of aspect 725, wherein the method increases effector T cell infiltration into the tumor by at least 15%.

[0809] 800. The method of aspect 725, wherein the agent or combination of agents is administered in a liposomal formulation.

[0810] 801. The method of aspect 725, wherein the senolytic agent is administered in a nanoparticle formulation.

[0811] 802. The method of aspect 725, wherein the method further comprises a step of identifying the subject as having a cancer with high senescent cell burden prior to administration.

[0812] 803. The method of aspect 802, wherein the senescent cell burden is determined by measuring the expression of at least one senescence marker selected from the group consisting of p16, p21, and SA-β-gal.

[0813] 804. The method of aspect 725, wherein the method further comprises a step of identifying the subject as having a high T regulatory cell number and / or activity in the tumor microenvironment prior to administration.

[0814] 805. The method of aspect 804, wherein the T regulatory cell number and / or activity is determined by measuring the expression of at least one marker selected from the group consisting of FoxP3, CD25, and CTLA-4.

[0815] 806. The method of aspect 725, wherein the agent or combination of agents has a purity of at least 90%.

[0816] 807. The method of aspect 725, wherein the senolytic agent and the agent or combination of agents are administered in a ratio ranging from 1: 10 to 10:1 by weight.

[0817] 808. The method of aspect 725, wherein the method further comprises administering a dietary supplement to the subject.

[0818] 809. The method of aspect 808, wherein the dietary supplement comprises at least one vitamin selected from the group consisting of vitamin C and vitamin D.

[0819] 810. The method of aspect 725, wherein the method further comprises subjecting the subject to radiation therapy.Immorta-ANKC-PCT

[0820] 811. The method of aspect 725, wherein the method further comprises surgically resecting a tumor from the subject prior to administration.

[0821] 812. The method of aspect 725, wherein the method is used as an adjuvant therapy following a primary cancer treatment.

[0822] 813. The method of aspect 725, wherein the method is used as a neoadjuvant therapy prior to a primary cancer treatment.

[0823] 814. The method of aspect 725, wherein the method reduces cancer recurrence rates by at least 10% compared to a control group not receiving the combination.

[0824] 815. The method of aspect 725, wherein the method is performed in combination with a ketogenic diet.

[0825] 816. The method of aspect 725, wherein the agent or combination of agents is administered via a transdermal patch.

[0826] 817. The method of aspect 725, wherein the senolytic agent is administered via inhalation.

[0827] 818. The method of aspect 725, wherein the method further comprises monitoring the subject for adverse effects.

[0828] 819. The method of aspect 818, wherein the adverse effects include at least one of hepatotoxicity, nephrotoxicity, and gastrointestinal distress.

[0829] 820. The method of aspect 725, wherein the method is performed in a subject with a genetic mutation associated with cancer.

[0830] 821. The method of aspect 820, wherein the genetic mutation is in a gene selected from the group consisting of BRCA1, BRCA2, and TP53.

[0831] 822. The method of aspect 725, wherein the method further comprises administering an NK cell-enhancing agent.

[0832] 823. The method of aspect 822, wherein the NK cell-enhancing agent is a naturally occurring compound selected from the group consisting of beta-glucans, curcumin, and resveratrol.

[0833] 824. The method of aspect 725, wherein the agent or combination of agents is administered in a sustained-release formulation.

[0834] 825. The method of aspect 725, wherein the senolytic agent is administered in an immediate-release formulation.

[0835] 826. The method of aspect 725, wherein the method reduces tumor-associated inflammation by at least 10%.Immorta-ANKC-PCT

[0836] 827. The method of aspect 725, wherein the method increases the subject’s quality of life as measured by a standardized quality-of-life index.

[0837] 828. The method of aspect 725, wherein the method further comprises administering a microbiome-modulating agent.

[0838] 829. The method of aspect 828, wherein the microbiome-modulating agent is a probiotic comprising at least one strain selected from the group consisting of Lactobacillus acidophilus and Bifidobacterium longum.

[0839] 830. The method of aspect 828, wherein the microbiome-modulating agent is a prebiotic selected from the group consisting of inulin, fructooligosaccharides (FOS), and galactooligosaccharides (GOS).

[0840] 831. The method of aspect 725, wherein the method further comprises administering a naturally occurring compound that activates NK cell tumor-killing ability.

[0841] 832. The method of aspect 831, wherein the naturally occurring compound is selected from the group consisting of beta-glucans, arabinogalactans, and fucoidans.

[0842] 833. The method of aspect 832, wherein the naturally occurring compound is a beta-glucan derived from a source selected from the group consisting of mushrooms, yeast, and oats.

[0843] 834. The method of aspect 833, wherein the beta-glucan is derived from a mushroom selected from the group consisting of reishi, shiitake, and maitake.

[0844] 835. The method of aspect 725, wherein the method further comprises administering a microbiome metabolite.

[0845] 836. The method of aspect 835, wherein the microbiome metabolite is a short-chain fatty acid selected from the group consisting of butyrate, propionate, and acetate.

[0846] 837. The method of aspect 836, wherein the short-chain fatty acid is butyrate.

[0847] 838. The method of aspect 725, wherein the method increases the ratio of effector T cells to T regulatory cells in the tumor microenvironment by at least 10%.

[0848] 839. The method of aspect 725, wherein the method further comprises administering an anti-inflammatory agent.

[0849] 840. The method of aspect 839, wherein the anti-inflammatory agent is selected from the group consisting of aspirin, ibuprofen, and celecoxib.

[0850] 841. The method of aspect 725, wherein the method further comprises administering an antioxidant.Immorta-ANKC-PCT

[0851] 842. The method of aspect 841, wherein the antioxidant is selected from the group consisting of N-acetylcysteine, glutathione, and coenzyme Q10.

[0852] 843. The method of aspect 725, wherein the method further comprises administering a vaccine.

[0853] 844. The method of aspect 843, wherein the vaccine is a cancer vaccine targeting at least one tumor-associated antigen.

[0854] 845. The method of aspect 844, wherein the tumor-associated antigen is selected from the group consisting of HER2, MUC1, and PSA.

[0855] 846. The method of aspect 725, wherein the method further comprises administering a CAR-T cell therapy.

[0856] 847. The method of aspect 725, wherein the method further comprises administering an oncolytic virus.

[0857] 848. The method of aspect 847, wherein the oncolytic virus is selected from the group consisting of talimogene laherparepvec, reovirus, and vaccinia virus.

[0858] 849. The method of aspect 725, wherein the method further comprises administering a histone deacetylase (HDAC) inhibitor.

[0859] 850. The method of aspect 849, wherein the HDAC inhibitor is selected from the group consisting of vorinostat, romidepsin, and panobinostat.

[0860] 851. The method of aspect 725, wherein the method further comprises administering a DNA methyltransferase inhibitor.

[0861] 852. The method of aspect 851, wherein the DNA methyltransferase inhibitor is selected from the group consisting of azacitidine and decitabine.

[0862] 853. The method of aspect 725, wherein the method further comprises administering a tyrosine kinase inhibitor.

[0863] 854. The method of aspect 853, wherein the tyrosine kinase inhibitor is selected from the group consisting of erlotinib, gefitinib, and osimertinib.

[0864] 855. The method of aspect 725, wherein the method further comprises administering a proteasome inhibitor.

[0865] 856. The method of aspect 855, wherein the proteasome inhibitor is selected from the group consisting of bortezomib, carfilzomib, and ixazomib.

[0866] 857. The method of aspect 725, wherein the method further comprises administering a PARP inhibitor.

[0867] 858. The method of aspect 857, wherein the PARP inhibitor is selected from the group consisting of olaparib, rucaparib, and niraparib.Immorta-ANKC-PCT

[0868] 859. The method of aspect 725, wherein the method further comprises administering a BCL-2 inhibitor.

[0869] 860. The method of aspect 859, wherein the BCL-2 inhibitor is venetoclax.

[0870] 861. The method of aspect 725, wherein the method further comprises administering an mTOR inhibitor.

[0871] 862. The method of aspect 861, wherein the mTOR inhibitor is selected from the group consisting of rapamycin, everolimus, and temsirolimus.

[0872] 863. The method of aspect 725, wherein the method further comprises administering a PI3K inhibitor.

[0873] 864. The method of aspect 863, wherein the PI3K inhibitor is selected from the group consisting of idelalisib, copanlisib, and duvelisib.

[0874] 865. The method of aspect 725, wherein the method further comprises administering a CDK4 / 6 inhibitor.

[0875] 866. The method of aspect 865, wherein the CDK4 / 6 inhibitor is selected from the group consisting of palbociclib, ribociclib, and abemaciclib.

[0876] 867. The method of aspect 725, wherein the method further comprises administering an anti -angiogenic agent.

[0877] 868. The method of aspect 867, wherein the anti -angiogenic agent is selected from the group consisting of bevacizumab, sorafenib, and lenvatinib.

[0878] 869. The method of aspect 725, wherein the method further comprises administering a bispecific antibody.

[0879] 870. The method of aspect 869, wherein the bispecific antibody targets at least one of CD3 and a tumor-associated antigen.

[0880] 871. The method of aspect 725, wherein the method further comprises administering an adoptive cell therapy.

[0881] 872. The method of aspect 871, wherein the adoptive cell therapy comprises NK cells.

[0882] 873. The method of aspect 725, wherein the method further comprises administering a tumor necrosis factor (TNF) superfamily agonist.

[0883] 874. The method of aspect 873, wherein the TNF superfamily agonist is a GITR agonist.

[0884] 875. The method of aspect 725, wherein the method further comprises administering a toll-like receptor (TLR) agonist.Immorta-ANKC-PCT

[0885] 876. The method of aspect 875, wherein the TLR agonist is selected from the group consisting of imiquimod, resiquimod, and CpG oligodeoxynucleotides.

[0886] 877. The method of aspect 725, wherein the method further comprises administering a STING agonist.

[0887] 878. The method of aspect 877, wherein the STING agonist is a cyclic dinucleotide.

[0888] 879. The method of aspect 725, wherein the method further comprises administering a chemotherapeutic agent that induces immunogenic cell death.

[0889] 880. The method of aspect 879, wherein the chemotherapeutic agent is selected from the group consisting of anthracyclines, oxaliplatin, and cyclophosphamide.

[0890] 881. The method of aspect 725, wherein the method further comprises administering a radiotherapy sensitizer.

[0891] 882. The method of aspect 881, wherein the radiotherapy sensitizer is a PARP inhibitor.

[0892] 883. The method of aspect 725, wherein the method further comprises administering a hypoxia-targeting agent.

[0893] 884. The method of aspect 883, wherein the hypoxia-targeting agent is tirapazamine.

[0894] 885. The method of aspect 725, wherein the method further comprises administering a cancer stem cell-targeting agent.

[0895] 886. The method of aspect 885, wherein the cancer stem cell-targeting agent targets at least one pathway selected from the group consisting of Wnt, Notch, and Hedgehog.

[0896] 887. The method of aspect 725, wherein the method further comprises administering a metabolic inhibitor.

[0897] 888. The method of aspect 887, wherein the metabolic inhibitor targets at least one of glycolysis, glutaminolysis, or fatty acid synthesis.

[0898] 889. The method of aspect 725, wherein the method further comprises administering an immune adjuvant.

[0899] 890. The method of aspect 889, wherein the immune adjuvant is selected from the group consisting of alum, MF59, and AS03.

[0900] 891. The method of aspect 725, wherein the method further comprises administering a peptide-based therapeutic.Immorta-ANKC-PCT

[0901] 892. The method of aspect 891, wherein the peptide-based therapeutic targets a tumor-associated antigen.

[0902] 893. The method of aspect 725, wherein the method further comprises administering a small interfering RNA (siRNA).

[0903] 894. The method of aspect 893, wherein the siRNA targets a gene associated with T regulatory cell function.

[0904] 895. The method of aspect 894, wherein the gene is selected from the group consisting of FoxP3, CTLA-4, and IL-10.

[0905] 896. The method of aspect 725, wherein the method further comprises administering a CRISPR-based therapeutic.

[0906] 897. The method of aspect 896, wherein the CRISPR-based therapeutic targets a gene associated with cancer cell survival.

[0907] 898. The method of aspect 897, wherein the gene is selected from the group consisting of MYC, KRAS, and EGFR.

[0908] 899. The method of aspect 725, wherein the method further comprises administering a nanoparticle-based therapeutic.

[0909] 900. The method of aspect 899, wherein the nanoparticle-based therapeutic delivers the agent or combination of agents capable of reducing T regulatory cell number and / or activity.

[0910] 901. The method of aspect 725, wherein the method further comprises administering a photodynamic therapy agent.

[0911] 902. The method of aspect 901, wherein the photodynamic therapy agent is a porphyrin derivative.

[0912] 903. The method of aspect 725, wherein the method further comprises administering a radiofrequency ablation therapy.

[0913] 904. The method of aspect 725, wherein the method further comprises administering a cryoablation therapy.

[0914] 905. The method of aspect 725, wherein the method further comprises administering a high-intensity focused ultrasound (HIFU) therapy.

[0915] 906. The method of aspect 725, wherein the method further comprises administering a laser interstitial thermal therapy (LITT).

[0916] 907. The method of aspect 725, wherein the method further comprises administering a targeted alpha therapy.Immorta-ANKC-PCT

[0917] 908. The method of aspect 907, wherein the targeted alpha therapy uses an isotope selected from the group consisting of actinium-225 and bismuth-213.

[0918] 909. The method of aspect 725, wherein the method further comprises administering a boron neutron capture therapy (BNCT).

[0919] 910. The method of aspect 725, wherein the method further comprises administering a proton therapy.

[0920] 911. The method of aspect 725, wherein the method further comprises administering a carbon ion therapy.

[0921] 912. The method of aspect 725, wherein the method further comprises administering a stereotactic radiosurgery.

[0922] 913. The method of aspect 725, wherein the method further comprises administering a brachytherapy.

[0923] 914. The method of aspect 725, wherein the method further comprises administering a gene therapy.

[0924] 915. The method of aspect 914, wherein the gene therapy introduces a gene encoding a cytokine that enhances anti-tumor immunity.

[0925] 916. The method of aspect 915, wherein the cytokine is selected from the group consisting of IL-12, GM-CSF, and IFN-γ.

[0926] 917. The method of aspect 725, wherein the method further comprises administering a viral vector-based therapy.

[0927] 918. The method of aspect 917, wherein the viral vector is an adeno-associated virus (AAV).

[0928] 919. The method of aspect 725, wherein the method further comprises administering a lipid nanoparticle-based therapy.

[0929] 920. The method of aspect 919, wherein the lipid nanoparticle delivers an mRNA encoding an immune-stimulatory protein.

[0930] 921. The method of aspect 725, wherein the method further comprises administering a dendritic cell-based therapy.

[0931] 922. The method of aspect 921, wherein the dendritic cell-based therapy involves dendritic cells pulsed with a tumor-associated antigen.

[0932] 923. The method of aspect 725, wherein the method further comprises administering a natural product-based therapeutic.

[0933] 924. The method of aspect 923, wherein the natural product-based therapeutic is derived from a plant source.Immorta-ANKC-PCT

[0934] 925. The method of aspect 924, wherein the plant source is selected from the group consisting of turmeric, green tea, and ginseng.

[0935] 926. A method of treating cancer in a subject in need thereof, the method comprising:administering to the subject a therapeutically effective amount of one or more senolytic agents; administering to the subject a therapeutically effective amount of one or more agents that activate NK cells; and administering to the subject a therapeutically effective amount of one or more agents that suppress myeloid-derived suppressor cell (MDSC) number and / or function,wherein the combination reduces cancer cell burden in the subject.

[0936] 927. The method of aspect 926, wherein the one or more senolytic agents selectively induce apoptosis in senescent cancer cells.

[0937] 928. The method of aspect 926, wherein the one or more senolytic agents are selected from the group consisting of dasatinib, quercetin, navitoclax, and fisetin.

[0938] 929. The method of aspect 928, wherein the one or more senolytic agents include dasatinib.

[0939] 930. The method of aspect 928, wherein the one or more senolytic agents include quercetin.

[0940] 931. The method of aspect 928, wherein the one or more senolytic agents include navitoclax.

[0941] 932. The method of aspect 928, wherein the one or more senolytic agents include fisetin.

[0942] 933. The method of aspect 926, wherein the one or more agents that activate NK cells are naturally occurring compounds.

[0943] 934. The method of aspect 933, wherein the naturally occurring compounds are selected from the group consisting of beta-glucans, arabinogalactans, fucoidans, curcumin, resveratrol, and epigallocatechin gallate (EGCG).

[0944] 935. The method of aspect 934, wherein the naturally occurring compound is a beta-glucan derived from a source selected from the group consisting of mushrooms, yeast, and oats.

[0945] 936. The method of aspect 935, wherein the beta-glucan is derived from a mushroom selected from the group consisting of reishi, shiitake, and maitake.

[0946] 937. The method of aspect 934, wherein the naturally occurring compound is curcumin.Immorta-ANKC-PCT

[0947] 938. The method of aspect 934, wherein the naturally occurring compound is resveratrol.

[0948] 939. The method of aspect 934, wherein the naturally occurring compound is epigallocatechin gallate (EGCG).

[0949] 940. The method of aspect 926, wherein the one or more agents that activate NK cells include a cytokine.

[0950] 941. The method of aspect 940, wherein the cytokine is selected from the group consisting of IL-2, IL- 15, and IL-21.

[0951] 942. The method of aspect 941, wherein the cytokine is IL-2.

[0952] 943. The method of aspect 941, wherein the cytokine is IL-15.

[0953] 944. The method of aspect 941, wherein the cytokine is IL-21.

[0954] 945. The method of aspect 926, wherein the one or more agents that activate NK cells upregulate the expression of at least one NK cell-activating receptor selected from the group consisting of NKG2D, NKp46, and NKp30.

[0955] 946. The method of aspect 926, wherein the one or more agents that activate NK cells increase NK cell cytotoxicity against cancer cells by at least 10% compared to NK cells not exposed to the agents.

[0956] 947. The method of aspect 926, wherein the one or more agents that suppress MDSC number and / or function are small molecules.

[0957] 948. The method of aspect 947, wherein the small molecules are selected from the group consisting of all-trans retinoic acid (ATRA), sildenafil, and gemcitabine.

[0958] 949. The method of aspect 948, wherein the small molecule is all-trans retinoic acid (ATRA).

[0959] 950. The method of aspect 948, wherein the small molecule is sildenafil.

[0960] 951. The method of aspect 948, wherein the small molecule is gemcitabine.

[0961] 952. The method of aspect 926, wherein the one or more agents that suppress MDSC number and / or function are monoclonal antibodies.

[0962] 953. The method of aspect 952, wherein the monoclonal antibodies target at least one MDSC marker selected from the group consisting of CD11b, Gr-1, and CSF1R.

[0963] 954. The method of aspect 953, wherein the monoclonal antibody targets CSF1R.

[0964] 955. The method of aspect 926, wherein the one or more agents that suppress MDSC number and / or function inhibit at least one MDSC-associated pathway selected from the group consisting of STAT3, NF-κB, and PI3K.Immorta-ANKC-PCT

[0965] 956. The method of aspect 926, wherein the one or more agents that suppress MDSC number and / or function reduce MDSC number in the tumor microenvironment by at least 15%.

[0966] 957. The method of aspect 926, wherein the one or more agents that suppress MDSC number and / or function reduce MDSC immunosuppressive activity by at least 10%.

[0967] 958. The method of aspect 926, wherein the cancer is a solid tumor.

[0968] 959. The method of aspect 958, wherein the solid tumor is selected from the group consisting of breast cancer, lung cancer, pancreatic cancer, colorectal cancer, and melanoma.

[0969] 960. The method of aspect 959, wherein the solid tumor is breast cancer.

[0970] 961. The method of aspect 959, wherein the solid tumor is lung cancer.

[0971] 962. The method of aspect 959, wherein the solid tumor is pancreatic cancer.

[0972] 963. The method of aspect 959, wherein the solid tumor is colorectal cancer.

[0973] 964. The method of aspect 959, wherein the solid tumor is melanoma.

[0974] 965. The method of aspect 926, wherein the cancer is a hematologic malignancy.

[0975] 966. The method of aspect 965, wherein the hematologic malignancy is selected from the group consisting of leukemia, lymphoma, and multiple myeloma.

[0976] 967. The method of aspect 966, wherein the hematologic malignancy is leukemia.

[0977] 968. The method of aspect 966, wherein the hematologic malignancy is lymphoma.

[0978] 969. The method of aspect 966, wherein the hematologic malignancy is multiple myeloma.

[0979] 970. The method of aspect 926, wherein the one or more senolytic agents, the one or more agents that activate NK cells, and the one or more agents that suppress MDSC number and / or function are administered simultaneously.

[0980] 971. The method of aspect 926, wherein the one or more senolytic agents, the one or more agents that activate NK cells, and the one or more agents that suppress MDSC number and / or function are administered sequentially.

[0981] 972. The method of aspect 971, wherein the one or more senolytic agents are administered prior to the one or more agents that activate NK cells and the one or more agents that suppress MDSC number and / or function.Immorta-ANKC-PCT

[0982] 973. The method of aspect 971, wherein the one or more agents that suppress MDSC number and / or function are administered prior to the one or more senolytic agents and the one or more agents that activate NK cells.

[0983] 974. The method of aspect 926, wherein the one or more senolytic agents are administered at a dose ranging from 0.1 mg / kg to 100 mg / kg of the subject’s body weight.

[0984] 975. The method of aspect 926, wherein the one or more agents that activate NK cells are administered at a dose ranging from 0.5 mg / kg to 200 mg / kg of the subject’s body weight.

[0985] 976. The method of aspect 926, wherein the one or more agents that suppress MDSC number and / or function are administered at a dose ranging from 0.01 mg / kg to 50 mg / kg of the subject’s body weight.

[0986] 977. The method of aspect 926, wherein the one or more senolytic agents are administered orally.

[0987] 978. The method of aspect 926, wherein the one or more agents that activate NK cells are administered intravenously.

[0988] 979. The method of aspect 926, wherein the one or more agents that suppress MDSC number and / or function are administered orally.

[0989] 980. The method of aspect 926, wherein the one or more senolytic agents, the one or more agents that activate NK cells, and the one or more agents that suppress MDSC number and / or function are administered as part of a single pharmaceutical composition.

[0990] 981. The method of aspect 980, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier.

[0991] 982. The method of aspect 926, wherein the one or more senolytic agents, the one or more agents that activate NK cells, and the one or more agents that suppress MDSC number and / or function are administered as separate pharmaceutical compositions.

[0992] 983. The method of aspect 926, wherein the administration occurs daily for a period of at least one week.

[0993] 984. The method of aspect 926, wherein the administration occurs weekly for a period of at least one month.

[0994] 985. The method of aspect 926, wherein the subject is a human.Immorta-ANKC-PCT

[0995] 986. The method of aspect 926, wherein the subject is a non-human mammal.

[0996] 987. The method of aspect 926, further comprising administering an additional therapeutic agent.

[0997] 988. The method of aspect 987, wherein the additional therapeutic agent is an immune checkpoint inhibitor.

[0998] 989. The method of aspect 988, wherein the immune checkpoint inhibitor targets at least one of PD-1, PD-L1, or CTLA-4.

[0999] 990. The method of aspect 989, wherein the immune checkpoint inhibitor is selected from the group consisting of pembrolizumab, nivolumab, and ipilimumab.

[1000] 991. The method of aspect 987, wherein the additional therapeutic agent is a chemotherapeutic agent.

[1001] 992. The method of aspect 991, wherein the chemotherapeutic agent is selected from the group consisting of paclitaxel, doxorubicin, and cisplatin.

[1002] 993. The method of aspect 926, further comprising monitoring the subject for a reduction in tumor size.

[1003] 994. The method of aspect 926, further comprising monitoring the subject for an increase in NK cell activity.

[1004] 995. The method of aspect 926, further comprising monitoring the subject for a reduction in MDSC number and / or function in the tumor microenvironment.

[1005] 996. The method of aspect 926, wherein the combination of the one or more senolytic agents, the one or more agents that activate NK cells, and the one or more agents that suppress MDSC number and / or function results in a synergistic effect on cancer cell reduction.

[1006] 997. The method of aspect 926, wherein the method increases the subject’s progression-free survival by at least 10% compared to treatment with the one or more senolytic agents alone.

[1007] 998. The method of aspect 926, wherein the method increases the subject’s overall survival by at least 10% compared to treatment with the one or more agents that activate NK cells alone.

[1008] 999. The method of aspect 926, wherein the cancer is metastatic.

[1009] 1000. The method of aspect 926, wherein the cancer is refractory to at least one prior therapy.Immorta-ANKC-PCT

[1010] 1001. The method of aspect 926, wherein the one or more senolytic agents target at least one pathway selected from the group consisting of Bcl-2, PI3K / AKT, and p53.

[1011] 1002. The method of aspect 926, wherein the method reduces the number of senescent cells in the tumor microenvironment by at least 20%.

[1012] 1003. The method of aspect 926, wherein the method increases NK cell infiltration into the tumor by at least 15%.

[1013] 1004. The method of aspect 926, wherein the one or more agents that activate NK cells are administered in a liposomal formulation.

[1014] 1005. The method of aspect 926, wherein the one or more senolytic agents are administered in a nanoparticle formulation.

[1015] 1006. The method of aspect 926, wherein the one or more agents that suppress MDSC number and / or function are administered in a sustained-release formulation.

[1016] 1007. The method of aspect 926, wherein the method further comprises a step of identifying the subject as having a cancer with high senescent cell burden prior to administration.

[1017] 1008. The method of aspect 1007, wherein the senescent cell burden is determined by measuring the expression of at least one senescence marker selected from the group consisting of p16, p21, and SA-β-gal.

[1018] 1009. The method of aspect 926, wherein the method further comprises a step of identifying the subject as having a high MDSC number and / or activity in the tumor microenvironment prior to administration.

[1019] 1010. The method of aspect 1009, wherein the MDSC number and / or activity is determined by measuring the expression of at least one MDSC marker selected from the group consisting of CD11b, Gr-1, and arginase- 1.

[1020] 1011. The method of aspect 926, wherein the method further comprises a step of identifying the subject as having low NK cell activity prior to administration.

[1021] 1012. The method of aspect 1011, wherein the NK cell activity is determined by measuring the expression of at least one NK cell activation marker selected from the group consisting of CD69 and CD107a.

[1022] 1013. The method of aspect 926, wherein the one or more agents that activate NK cells have a purity of at least 90%.Immorta-ANKC-PCT

[1023] 1014. The method of aspect 926, wherein the one or more senolytic agents and the one or more agents that activate NK cells are administered in a ratio ranging from 1:10 to 10:1 by weight.

[1024] 1015. The method of aspect 926, wherein the one or more agents that suppress MDSC number and / or function and the one or more agents that activate NK cells are administered in a ratio ranging from 1:5 to 5: 1 by weight.

[1025] 1016. The method of aspect 926, wherein the method further comprises administering a dietary supplement to the subject.

[1026] 1017. The method of aspect 1016, wherein the dietary supplement comprises at least one vitamin selected from the group consisting of vitamin C and vitamin D.

[1027] 1018. The method of aspect 926, wherein the method further comprises subjecting the subject to radiation therapy.

[1028] 1019. The method of aspect 926, wherein the method further comprises surgically resecting a tumor from the subject prior to administration.

[1029] 1020. The method of aspect 926, wherein the method is used as an adjuvant therapy following a primary cancer treatment.

[1030] 1021. The method of aspect 926, wherein the method is used as a neoadjuvant therapy prior to a primary cancer treatment.

[1031] 1022. The method of aspect 926, wherein the method reduces cancer recurrence rates by at least 10% compared to a control group not receiving the combination.

[1032] 1023. The method of aspect 926, wherein the method is performed in combination with a ketogenic diet.

[1033] 1024. The method of aspect 926, wherein the method further comprises administering an agent capable of reducing T regulatory cell number and / or activity.

[1034] 1025. The method of aspect 1024, wherein the agent capable of reducing T regulatory cell number and / or activity is selected from the group consisting of cyclophosphamide, ipilimumab, and pembrolizumab.

[1035] 1026. A method of treating cancer by activating memory NK cells in the presence of one or more senolytics.

[1036] 1027. The method of aspect 1026, wherein the one or more senolytic agents selectively induce apoptosis in senescent cancer cells.

[1037] 1028. The method of aspect 1026, wherein the one or more senolytic agents are selected from the group consisting of dasatinib, quercetin, navitoclax, and fisetin.Immorta-ANKC-PCT

[1038] 1029. The method of aspect 1028, wherein the one or more senolytic agents include dasatinib.

[1039] 1030. The method of aspect 1028, wherein the one or more senolytic agents include quercetin.

[1040] 1031. The method of aspect 1028, wherein the one or more senolytic agents include navitoclax.

[1041] 1032. The method of aspect 1028, wherein the one or more senolytic agents include fisetin.

[1042] 1033. The method of aspect 1026, wherein the one or more agents that activate memory NK cells are cytokines.

[1043] 1034. The method of aspect 1033, wherein the cytokines are selected from the group consisting of IL- 12, IL- 15, and IL-18.

[1044] 1035. The method of aspect 1034, wherein the cytokine is IL- 12.

[1045] 1036. The method of aspect 1034, wherein the cytokine is IL-15.

[1046] 1037. The method of aspect 1034, wherein the cytokine is IL-18.

[1047] 1038. The method of aspect 1026, wherein the one or more agents that activate memory NK cells are naturally occurring compounds.

[1048] 1039. The method of aspect 1038, wherein the naturally occurring compounds are selected from the group consisting of beta-glucans, arabinogalactans, and fucoidans.

[1049] 1040. The method of aspect 1039, wherein the naturally occurring compound is a beta-glucan derived from a source selected from the group consisting of mushrooms, yeast, and oats.

[1050] 1041. The method of aspect 1040, wherein the beta-glucan is derived from a mushroom selected from the group consisting of reishi, shiitake, and maitake.

[1051] 1042. The method of aspect 1026, wherein the one or more agents that activate memory NK cells include a monoclonal antibody.

[1052] 1043. The method of aspect 1042, wherein the monoclonal antibody targets at least one NK cell-activating receptor selected from the group consisting of NKG2D, NKp46, and NKp30.

[1053] 1044. The method of aspect 1026, wherein the one or more agents that activate memory NK cells increase the expression of at least one memory NK cell marker selected from the group consisting of CD57, NKG2C, and FcyRIIIa.Immorta-ANKC-PCT

[1054] 1045. The method of aspect 1026, wherein the one or more agents that activate memory NK cells increase memory NK cell cytotoxicity against cancer cells by at least 10% compared to memory NK cells not exposed to the agents.

[1055] 1046. The method of aspect 1026, wherein the cancer is a solid tumor.

[1056] 1047. The method of aspect 1046, wherein the solid tumor is selected from the group consisting of breast cancer, lung cancer, pancreatic cancer, colorectal cancer, and melanoma.

[1057] 1048. The method of aspect 1047, wherein the solid tumor is breast cancer.

[1058] 1049. The method of aspect 1047, wherein the solid tumor is lung cancer.

[1059] 1050. The method of aspect 1047, wherein the solid tumor is pancreatic cancer.

[1060] 1051. The method of aspect 1047, wherein the solid tumor is colorectal cancer.

[1061] 1052. The method of aspect 1047, wherein the solid tumor is melanoma.

[1062] 1053. The method of aspect 1026, wherein the cancer is a hematologic malignancy.

[1063] 1054. The method of aspect 1053, wherein the hematologic malignancy is selected from the group consisting of leukemia, lymphoma, and multiple myeloma.

[1064] 1055. The method of aspect 1054, wherein the hematologic malignancy is leukemia.

[1065] 1056. The method of aspect 1054, wherein the hematologic malignancy is lymphoma.

[1066] 1057. The method of aspect 1054, wherein the hematologic malignancy is multiple myeloma.

[1067] 1058. The method of aspect 1026, wherein the one or more senolytic agents and the one or more agents that activate memory NK cells are administered simultaneously.

[1068] 1059. The method of aspect 1026, wherein the one or more senolytic agents and the one or more agents that activate memory NK cells are administered sequentially.

[1069] 1060. The method of aspect 1059, wherein the one or more senolytic agents are administered prior to the one or more agents that activate memory NK cells.

[1070] 1061. The method of aspect 1059, wherein the one or more agents that activate memory NK cells are administered prior to the one or more senolytic agents.Immorta-ANKC-PCT

[1071] 1062. The method of aspect 1026, wherein the one or more senolytic agents are administered at a dose ranging from 0.1 mg / kg to 100 mg / kg of the subject’s body weight.

[1072] 1063. The method of aspect 1026, wherein the one or more agents that activate memory NK cells are administered at a dose ranging from 0.5 mg / kg to 200 mg / kg of the subject’s body weight.

[1073] 1064. The method of aspect 1026, wherein the one or more senolytic agents are administered orally.

[1074] 1065. The method of aspect 1026, wherein the one or more agents that activate memory NK cells are administered intravenously.

[1075] 1066. The method of aspect 1026, wherein the one or more senolytic agents and the one or more agents that activate memory NK cells are administered as part of a single pharmaceutical composition.

[1076] 1067. The method of aspect 1066, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier.

[1077] 1068. The method of aspect 1026, wherein the one or more senolytic agents and the one or more agents that activate memory NK cells are administered as separate pharmaceutical compositions.

[1078] 1069. The method of aspect 1026, wherein the administration occurs daily for a period of at least one week.

[1079] 1070. The method of aspect 1026, wherein the administration occurs weekly for a period of at least one month.

[1080] 1071. The method of aspect 1026, wherein the subject is a human.

[1081] 1072. The method of aspect 1026, wherein the subject is a non-human mammal.

[1082] 1073. The method of aspect 1026, further comprising administering an additional therapeutic agent.

[1083] 1074. The method of aspect 1073, wherein the additional therapeutic agent is an immune checkpoint inhibitor selected from the group consisting of pembrolizumab, nivolumab, and ipilimumab.

[1084] 1075. The method of aspect 1026, wherein the method increases the subject’s progression-free survival by at least 10% compared to treatment with the one or more senolytic agents alone.Immorta-ANKC-PCT

[1085] 1076. A method of stimulating T cell responses against tumors by inducing endogenous NK cell activation and / or administration of exogenous NK cells, either allogeneic or autologous, in the presence of one or more senolytic compounds and / or therapies.

[1086] 1076. A method of stimulating T cell responses against tumors in a subject in need thereof, the method comprising: administering to the subject a therapeutically effective amount of one or more senolytic compounds and / or therapies; and inducing endogenous NK cell activation and / or administering a therapeutically effective amount of exogenous NK cells, wherein the exogenous NK cells are allogeneic or autologous, wherein the method stimulates T cell responses against tumors in the subject.

[1087] 1077. The method of aspect 1076, wherein the one or more senolytic compounds selectively induce apoptosis in senescent tumor cells.

[1088] 1078. The method of aspect 1076, wherein the one or more senolytic compounds are selected from the group consisting of dasatinib, quercetin, navitoclax, and fisetin.

[1089] 1079. The method of aspect 1078, wherein the one or more senolytic compounds include dasatinib.

[1090] 1080. The method of aspect 1078, wherein the one or more senolytic compounds include quercetin.

[1091] 1081. The method of aspect 1078, wherein the one or more senolytic compounds include navitoclax.

[1092] 1082. The method of aspect 1078, wherein the one or more senolytic compounds include fisetin.

[1093] 1083. The method of aspect 1076, wherein the one or more senolytic therapies include a non-pharmacological intervention.

[1094] 1084. The method of aspect 1083, wherein the non-pharmacological intervention is fasting or a fasting-mimicking diet.

[1095] 1085. The method of aspect 1076, wherein inducing endogenous NK cell activation comprises administering one or more NK cell-activating agents.

[1096] 1086. The method of aspect 1085, wherein the one or more NK cellactivating agents are naturally occurring compounds.

[1097] 1087. The method of aspect 1086, wherein the naturally occurring compounds are selected from the group consisting of beta-glucans, arabinogalactans, fucoidans, curcumin, resveratrol, and epigallocatechin gallate (EGCG).Immorta-ANKC-PCT

[1098] 1088. The method of aspect 1087, wherein the naturally occurring compound is a beta-glucan derived from a source selected from the group consisting of mushrooms, yeast, and oats.

[1099] 1089. The method of aspect 1088, wherein the beta-glucan is derived from a mushroom selected from the group consisting of reishi, shiitake, and maitake.

[1100] 1090. The method of aspect 1087, wherein the naturally occurring compound is curcumin.[HOI] 1091. The method of aspect 1087, wherein the naturally occurring compound is resveratrol.

[1102] 1092. The method of aspect 1087, wherein the naturally occurring compound is epigallocatechin gallate (EGCG).

[1103] 1093. The method of aspect 1085, wherein the one or more NK cellactivating agents include a cytokine.

[1104] 1094. The method of aspect 1093, wherein the cytokine is selected from the group consisting of IL-2, IL- 15, IL- 18, and IL-21.

[1105] 1095. The method of aspect 1094, wherein the cytokine is IL-2.

[1106] 1096. The method of aspect 1094, wherein the cytokine is IL-15.

[1107] 1097. The method of aspect 1094, wherein the cytokine is IL-18.

[1108] 1098. The method of aspect 1094, wherein the cytokine is IL-21.

[1109] 1099. The method of aspect 1085, wherein the one or more NK cellactivating agents include a monoclonal antibody.

[1110] 1100. The method of aspect 1099, wherein the monoclonal antibody targets at least one NK cell-activating receptor selected from the group consisting of NKG2D, NKp46, and NKp30.

[1111] 1101. The method of aspect 1076, wherein inducing endogenous NK cell activation comprises upregulating the expression of at least one NK cell-activating receptor selected from the group consisting of NKG2D, NKp46, and NKp30.

[1112] 1102. The method of aspect 1076, wherein inducing endogenous NK cell activation increases NK cell cytotoxicity against tumor cells by at least 10% compared to NK cells not exposed to the activation method.

[1113] 1103. The method of aspect 1076, wherein the exogenous NK cells are autologous.

[1114] 1104. The method of aspect 1076, wherein the exogenous NK cells are allogeneic.Immorta-ANKC-PCT

[1115] 1105. The method of aspect 1104, wherein the allogeneic NK cells are derived from a healthy donor.

[1116] 1106. The method of aspect 1104, wherein the allogeneic NK cells are derived from an induced pluripotent stem cell (iPSC) source.

[1117] 1107. The method of aspect 1076, wherein the exogenous NK cells are genetically modified.

[1118] 1108. The method of aspect 1107, wherein the exogenous NK cells are modified to express a chimeric antigen receptor (CAR).

[1119] 1109. The method of aspect 1108, wherein the CAR targets a tumor-associated antigen selected from the group consisting of CD 19, HER2, and EGFR.

[1120] 1110. The method of aspect 1107, wherein the exogenous NK cells are modified to overexpress at least one NK cell-activating receptor selected from the group consisting of NKG2D, NKp46, and NKp30.

[1121] 1111. The method of aspect 1076, wherein the exogenous NK cells are expanded ex vivo prior to administration.

[1122] 1112. The method of aspect 1111, wherein the ex vivo expansion includes culturing the NK cells in the presence of at least one cytokine selected from the group consisting of IL-2, IL- 15, and IL-21.

[1123] 1113. The method of aspect 1076, wherein the exogenous NK cells are administered at a dose ranging from 1 x 106to 1 x 109cells per kg of the subject’s body weight.

[1124] 1114. The method of aspect 1076, wherein the method stimulates CD8+ T cell responses against tumors.

[1125] 1115. The method of aspect 1076, wherein the method stimulates CD4+ T cell responses against tumors.

[1126] 1116. The method of aspect 1076, wherein the method increases the production of at least one T cell-derived cytokine selected from the group consisting of IFN-γ, TNF-a, and IL-2 by at least 10%.

[1127] 1117. The method of aspect 1076, wherein the method increases T cell infiltration into the tumor by at least 15%.

[1128] 1118. The method of aspect 1076, wherein the tumor is a solid tumor.

[1129] 1119. The method of aspect 1118, wherein the solid tumor is selected from the group consisting of breast cancer, lung cancer, pancreatic cancer, colorectal cancer, and melanoma.Immorta-ANKC-PCT

[1130] 1120. The method of aspect 1119, wherein the solid tumor is breast cancer.

[1131] 1121. The method of aspect 1119, wherein the solid tumor is lung cancer.

[1132] 1122. The method of aspect 1119, wherein the solid tumor is pancreatic cancer.

[1133] 1123. The method of aspect 1119, wherein the solid tumor is colorectal cancer.

[1134] 1124. The method of aspect 1119, wherein the solid tumor is melanoma.

[1135] 1125. The method of aspect 1076, wherein the tumor is a hematologic malignancy.

[1136] 1126. The method of aspect 1125, wherein the hematologic malignancy is selected from the group consisting of leukemia, lymphoma, and multiple myeloma.

[1137] 1127. The method of aspect 1126, wherein the hematologic malignancy is leukemia.

[1138] 1128. The method of aspect 1126, wherein the hematologic malignancy is lymphoma.

[1139] 1129. The method of aspect 1126, wherein the hematologic malignancy is multiple myeloma.

[1140] 1130. The method of aspect 1076, wherein the one or more senolytic compounds and the step of inducing endogenous NK cell activation and / or administering exogenous NK cells are performed simultaneously.

[1141] 1131. The method of aspect 1076, wherein the one or more senolytic compounds and the step of inducing endogenous NK cell activation and / or administering exogenous NK cells are performed sequentially.

[1142] 1132. The method of aspect 1131, wherein the one or more senolytic compounds are administered prior to inducing endogenous NK cell activation and / or administering exogenous NK cells.

[1143] 1133. The method of aspect 1131, wherein inducing endogenous NK cell activation and / or administering exogenous NK cells occurs prior to administering the one or more senolytic compounds.

[1144] 1134. The method of aspect 1076, wherein the one or more senolytic compounds are administered at a dose ranging from 0.1 mg / kg to 100 mg / kg of the subject’s body weight.Immorta-ANKC-PCT

[1145] 1135. The method of aspect 1076, wherein inducing endogenous NK cell activation comprises administering one or more NK cell-activating agents at a dose ranging from 0.5 mg / kg to 200 mg / kg of the subject’s body weight.

[1146] 1136. The method of aspect 1076, wherein the one or more senolytic compounds are administered orally.

[1147] 1137. The method of aspect 1076, wherein the one or more senolytic compounds are administered intravenously.

[1148] 1138. The method of aspect 1076, wherein inducing endogenous NK cell activation comprises administering one or more NK cell-activating agents intravenously.

[1149] 1139. The method of aspect 1076, wherein the exogenous NK cells are administered intravenously.

[1150] 1140. The method of aspect 1076, wherein the one or more senolytic compounds and the one or more NK cell-activating agents are administered as part of a single pharmaceutical composition.

[1151] 1141. The method of aspect 1140, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier.

[1152] 1142. The method of aspect 1076, wherein the one or more senolytic compounds and the one or more NK cell-activating agents are administered as separate pharmaceutical compositions.

[1153] 1143. The method of aspect 1076, wherein the administration occurs daily for a period of at least one week.

[1154] 1144. The method of aspect 1076, wherein the administration occurs weekly for a period of at least one month.

[1155] 1145. The method of aspect 1076, wherein the subject is a human.

[1156] 1146. The method of aspect 1076, wherein the subject is a non-human mammal.

[1157] 1147. The method of aspect 1076, further comprising administering an additional therapeutic agent.

[1158] 1148. The method of aspect 1147, wherein the additional therapeutic agent is an immune checkpoint inhibitor.

[1159] 1149. The method of aspect 1148, wherein the immune checkpoint inhibitor targets at least one of PD-1, PD-L1, or CTLA-4.

[1160] 1150. The method of aspect 1149, wherein the immune checkpoint inhibitor is selected from the group consisting of pembrolizumab, nivolumab, and ipilimumab.Immorta-ANKC-PCT

[1161] 1151. The method of aspect 1147, wherein the additional therapeutic agent is a chemotherapeutic agent.

[1162] 1152. The method of aspect 1151, wherein the chemotherapeutic agent is selected from the group consisting of paclitaxel, doxorubicin, and cisplatin.

[1163] 1153. The method of aspect 1076, further comprising monitoring the subject for an increase in T cell responses against tumors.

[1164] 1154. The method of aspect 1153, wherein the T cell responses are measured by an increase in T cell proliferation by at least 10%.

[1165] 1155. The method of aspect 1076, further comprising monitoring the subject for an increase in NK cell activity.

[1166] 1156. The method of aspect 1076, further comprising monitoring the subject for a reduction in tumor size.

[1167] 1157. The method of aspect 1076, wherein the combination of the one or more senolytic compounds and / or therapies and inducing endogenous NK cell activation and / or administering exogenous NK cells results in a synergistic effect on stimulating T cell responses against tumors.

[1168] 1158. The method of aspect 1076, wherein the method increases the subject’s progression-free survival by at least 10% compared to treatment with the one or more senolytic compounds and / or therapies alone.

[1169] 1159. The method of aspect 1076, wherein the method increases the subject’s overall survival by at least 10% compared to treatment without inducing endogenous NK cell activation or administering exogenous NK cells.

[1170] 1160. The method of aspect 1076, wherein the tumor is metastatic.

[1171] 1161. The method of aspect 1076, wherein the tumor is refractory to at least one prior therapy.

[1172] 1162. The method of aspect 1076, wherein the one or more senolytic compounds target at least one pathway selected from the group consisting of Bcl-2, PI3K / AKT, and p53.

[1173] 1163. The method of aspect 1076, wherein the method reduces the number of senescent cells in the tumor microenvironment by at least 20%.

[1174] 1164. The method of aspect 1076, wherein the method increases NK cell infiltration into the tumor by at least 15%.

[1175] 1165. The method of aspect 1076, wherein the one or more senolytic compounds are administered in a nanoparticle formulation.Immorta-ANKC-PCT

[1176] 1166. The method of aspect 1076, wherein inducing endogenous NK cell activation comprises administering one or more NK cell-activating agents in a liposomal formulation.

[1177] 1167. The method of aspect 1076, wherein the exogenous NK cells are cryopreserved prior to administration.

[1178] 1168. The method of aspect 1076, wherein the method further comprises a step of identifying the subject as having a tumor with high senescent cell burden prior to administration.

[1179] 1169. The method of aspect 1168, wherein the senescent cell burden is determined by measuring the expression of at least one senescence marker selected from the group consisting of p16, p21, and SA-β-gal.

[1180] 1170. The method of aspect 1076, wherein the method further comprises a step of identifying the subject as having low NK cell activity prior to administration.

[1181] 1171. The method of aspect 1170, wherein the NK cell activity is determined by measuring the expression of at least one NK cell activation marker selected from the group consisting of CD69 and CD107a.

[1182] 1172. The method of aspect 1076, wherein the method further comprises a step of identifying the subject as having low T cell responses against tumors prior to administration.

[1183] 1173. The method of aspect 1172, wherein the T cell responses are measured by assessing the expression of at least one T cell activation marker selected from the group consisting of CD25, CD69, and IFN-γ.

[1184] 1174. The method of aspect 1076, wherein the one or more senolytic compounds have a purity of at least 90%.

[1185] 1175. The method of aspect 1076, wherein the one or more senolytic compounds and the one or more NK cell-activating agents are administered in a ratio ranging from 1: 10 to 10:1 by weight.

[1186] 1176. The method of aspect 1076, wherein the method further comprises administering a dietary supplement to the subject.

[1187] 1177. The method of aspect 1176, wherein the dietary supplement comprises at least one vitamin selected from the group consisting of vitamin C and vitamin D.

[1188] 1178. The method of aspect 1076, wherein the method further comprises subjecting the subject to radiation therapy.Immorta-ANKC-PCT

[1189] 1179. The method of aspect 1076, wherein the method further comprises surgically resecting a tumor from the subject prior to administration.

[1190] 1180. The method of aspect 1076, wherein the method is used as an adjuvant therapy following a primary cancer treatment.

[1191] 1181. The method of aspect 1076, wherein the method is used as a neoadjuvant therapy prior to a primary cancer treatment.

[1192] 1182. The method of aspect 1076, wherein the method reduces cancer recurrence rates by at least 10% compared to a control group not receiving the combination.

[1193] 1183. The method of aspect 1076, wherein the method is performed in combination with a ketogenic diet.

[1194] 1184. The method of aspect 1076, wherein the method further comprises administering an agent capable of reducing T regulatory cell number and / or activity.

[1195] 1185. The method of aspect 1184, wherein the agent capable of reducing T regulatory cell number and / or activity is selected from the group consisting of cyclophosphamide, ipilimumab, and pembrolizumab.

[1196] 1186. The method of aspect 1076, wherein the method further comprises administering an agent that suppresses myeloid-derived suppressor cell (MDSC) number and / or function.

[1197] 1187. The method of aspect 1186, wherein the agent that suppresses MDSC number and / or function is selected from the group consisting of all-trans retinoic acid (ATRA), sildenafil, and gemcitabine.

[1198] 1188. The method of aspect 1076, wherein the method further comprises administering a microbiome metabolite.

[1199] 1189. The method of aspect 1188, wherein the microbiome metabolite is a short-chain fatty acid selected from the group consisting of butyrate, propionate, and acetate.

[1200] 1190. The method of aspect 1076, wherein the method further comprises administering an agent that activates memory NK cells.

[1201] 1191. The method of aspect 1190, wherein the agent that activates memory NK cells is a cytokine selected from the group consisting of IL- 12, IL- 15, and IL- 18.

[1202] 1192. The method of aspect 1076, wherein the method further comprises administering an anti-inflammatory agent.Immorta-ANKC-PCT

[1203] 1193. The method of aspect 1192, wherein the anti-inflammatory agent is selected from the group consisting of aspirin, ibuprofen, and celecoxib.

[1204] 1194. The method of aspect 1076, wherein the method further comprises administering an antioxidant.

[1205] 1195. The method of aspect 1194, wherein the antioxidant is selected from the group consisting of N-acetylcysteine, glutathione, and coenzyme Q10.

[1206] 1196. The method of aspect 1076, wherein the method further comprises administering a cancer vaccine.

[1207] 1197. The method of aspect 1196, wherein the cancer vaccine targets a tumor-associated antigen selected from the group consisting of HER2, MUC1, and PSA.

[1208] 1198. The method of aspect 1076, wherein the method further comprises administering a CAR-T cell therapy.

[1209] 1199. The method of aspect 1076, wherein the method further comprises administering an oncolytic virus.

[1210] 1200. The method of aspect 1199, wherein the oncolytic virus is selected from the group consisting of talimogene laherparepvec, reovirus, and vaccinia virus.

[1211] 1201. The method of aspect 1076, wherein the method further comprises administering a histone deacetylase (HDAC) inhibitor.

[1212] 1202. The method of aspect 1201, wherein the HDAC inhibitor is selected from the group consisting of vorinostat, romidepsin, and panobinostat.

[1213] 1203. The method of aspect 1076, wherein the method further comprises administering a DNA methyltransferase inhibitor.

[1214] 1204. The method of aspect 1203, wherein the DNA methyltransferase inhibitor is selected from the group consisting of azacitidine and decitabine.

[1215] 1205. The method of aspect 1076, wherein the method further comprises administering a tyrosine kinase inhibitor.

[1216] 1206. The method of aspect 1205, wherein the tyrosine kinase inhibitor is selected from the group consisting of erlotinib, gefitinib, and osimertinib.

[1217] 1207. The method of aspect 1076, wherein the method further comprises administering a proteasome inhibitor.

[1218] 1208. The method of aspect 1207, wherein the proteasome inhibitor is selected from the group consisting of bortezomib, carfilzomib, and ixazomib.

[1219] 1209. The method of aspect 1076, wherein the method further comprises administering a PARP inhibitor.Immorta-ANKC-PCT

[1220] 1210. The method of aspect 1209, wherein the PARP inhibitor is selected from the group consisting of olaparib, rucaparib, and niraparib.

[1221] 1211. The method of aspect 1076, wherein the method further comprises administering a BCL-2 inhibitor.

[1222] 1212. The method of aspect 1211, wherein the BCL-2 inhibitor is venetoclax.

[1223] 1213. The method of aspect 1076, wherein the method further comprises administering an mTOR inhibitor.

[1224] 1214. The method of aspect 1213, wherein the mTOR inhibitor is selected from the group consisting of rapamycin, everolimus, and temsirolimus.

[1225] 1215. The method of aspect 1076, wherein the method further comprises administering a PI3K inhibitor.

[1226] 1216. The method of aspect 1215, wherein the PI3K inhibitor is selected from the group consisting of idelalisib, copanlisib, and duvelisib.

[1227] 1217. The method of aspect 1076, wherein the method further comprises administering a CDK4 / 6 inhibitor.

[1228] 1218. The method of aspect 1217, wherein the CDK4 / 6 inhibitor is selected from the group consisting of palbociclib, ribociclib, and abemaciclib.

[1229] 1219. The method of aspect 1076, wherein the method further comprises administering an anti -angiogenic agent.

[1230] 1220. The method of aspect 1219, wherein the anti-angiogenic agent is selected from the group consisting of bevacizumab, sorafenib, and lenvatinib.

[1231] 1221. The method of aspect 1076, wherein the method further comprises administering a bispecific antibody.

[1232] 1222. The method of aspect 1221, wherein the bispecific antibody targets at least one of CD3 and a tumor-associated antigen.

[1233] 1223. The method of aspect 1076, wherein the method further comprises administering an adoptive cell therapy.

[1234] 1224. The method of aspect 1223, wherein the adoptive cell therapy comprises T cells.

[1235] 1225. The method of aspect 1076, wherein the method further comprises administering a tumor necrosis factor (TNF) superfamily agonist.

[1236] 1226. The method of aspect 1225, wherein the TNF superfamily agonist is a GITR agonist.Immorta-ANKC-PCT

[1237] 1227. The method of aspect 1076, wherein the method further comprises administering a toll-like receptor (TLR) agonist.

[1238] 1228. The method of aspect 1227, wherein the TLR agonist is selected from the group consisting of imiquimod, resiquimod, and CpG oligodeoxynucleotides.

[1239] 1229. The method of aspect 1076, wherein the method further comprises administering a STING agonist.

[1240] 1230. The method of aspect 1229, wherein the STING agonist is a cyclic dinucleotide.

[1241] 1231. The method of aspect 1076, wherein the method further comprises administering a chemotherapeutic agent that induces immunogenic cell death.

[1242] 1232. The method of aspect 1231, wherein the chemotherapeutic agent is selected from the group consisting of anthracyclines, oxaliplatin, and cyclophosphamide.

[1243] 1233. The method of aspect 1076, wherein the method further comprises administering a radiotherapy sensitizer.

[1244] 1234. The method of aspect 1233, wherein the radiotherapy sensitizer is a PARP inhibitor.

[1245] 1235. The method of aspect 1076, wherein the method further comprises administering a hypoxia-targeting agent.

[1246] 1236. The method of aspect 1235, wherein the hypoxia-targeting agent is tirapazamine.

[1247] 1237. The method of aspect 1076, wherein the method further comprises administering a cancer stem cell-targeting agent.

[1248] 1238. The method of aspect 1237, wherein the cancer stem cell-targeting agent targets at least one pathway selected from the group consisting of Wnt, Notch, and Hedgehog.

[1249] 1239. The method of aspect 1076, wherein the method further comprises administering a metabolic inhibitor.

[1250] 1240. The method of aspect 1239, wherein the metabolic inhibitor targets at least one of glycolysis, glutaminolysis, or fatty acid synthesis.

[1251] 1241. The method of aspect 1076, wherein the method further comprises administering an immune adjuvant.

[1252] 1242. The method of aspect 1241, wherein the immune adjuvant is selected from the group consisting of alum, MF59, and AS03.Immorta-ANKC-PCT

[1253] 1243. The method of aspect 1076, wherein the method further comprises administering a peptide-based therapeutic.

[1254] 1244. The method of aspect 1243, wherein the peptide-based therapeutic targets a tumor-associated antigen.

[1255] 1245. The method of aspect 1076, wherein the method further comprises administering a small interfering RNA (siRNA).

[1256] 1246. The method of aspect 1245, wherein the siRNA targets a gene associated with tumor cell survival.

[1257] 1247. The method of aspect 1246, wherein the gene is selected from the group consisting of MYC, KRAS, and EGFR.

[1258] 1248. The method of aspect 1076, wherein the method further comprises administering a CRISPR-based therapeutic.

[1259] 1249. The method of aspect 1248, wherein the CRISPR-based therapeutic targets a gene associated with tumor cell survival.

[1260] 1250. The method of aspect 1249, wherein the gene is selected from the group consisting of MYC, KRAS, and EGFR.

[1261] 1251. The method of aspect 1076, wherein the method further comprises administering a nanoparticle-based therapeutic.

[1262] 1252. The method of aspect 1251, wherein the nanoparticle-based therapeutic delivers the one or more NK cell-activating agents.

[1263] 1253. The method of aspect 1076, wherein the method further comprises administering a photodynamic therapy agent.

[1264] 1254. The method of aspect 1253, wherein the photodynamic therapy agent is a porphyrin derivative.

[1265] 1255. The method of aspect 1076, wherein the method further comprises administering a radiofrequency ablation therapy.

[1266] 1256. The method of aspect 1076, wherein the method further comprises administering a cryoablation therapy.

[1267] 1257. The method of aspect 1076, wherein the method further comprises administering a high-intensity focused ultrasound (HIFU) therapy.

[1268] 1258. The method of aspect 1076, wherein the method further comprises administering a laser interstitial thermal therapy (LITT).

[1269] 1259. The method of aspect 1076, wherein the method further comprises administering a targeted alpha therapy.Immorta-ANKC-PCT

[1270] 1260. The method of aspect 1259, wherein the targeted alpha therapy uses an isotope selected from the group consisting of actinium-225 and bismuth-213.

[1271] 1261. The method of aspect 1076, wherein the method further comprises administering a boron neutron capture therapy (BNCT).

[1272] 1262. The method of aspect 1076, wherein the method further comprises administering a proton therapy.

[1273] 1263. The method of aspect 1076, wherein the method further comprises administering a carbon ion therapy.

[1274] 1264. The method of aspect 1076, wherein the method further comprises administering a stereotactic radiosurgery.

[1275] 1265. The method of aspect 1076, wherein the method further comprises administering a brachytherapy.

[1276] 1266. The method of aspect 1076, wherein the method further comprises administering a gene therapy.

[1277] 1267. The method of aspect 1266, wherein the gene therapy introduces a gene encoding a cytokine that enhances anti-tumor immunity.

[1278] 1268. The method of aspect 1267, wherein the cytokine is selected from the group consisting of IL-12, GM-CSF, and IFN-γ.

[1279] 1269. The method of aspect 1076, wherein the method further comprises administering a viral vector-based therapy.

[1280] 1270. The method of aspect 1269, wherein the viral vector is an adeno-associated virus (AAV).

[1281] 1271. The method of aspect 1076, wherein the method further comprises administering a lipid nanoparticle-based therapy.

[1282] 1272. The method of aspect 1271, wherein the lipid nanoparticle delivers an mRNA encoding an immune-stimulatory protein.

[1283] 1273. The method of aspect 1076, wherein the method further comprises administering a dendritic cell-based therapy.

[1284] 1274. The method of aspect 1273, wherein the dendritic cell-based therapy involves dendritic cells pulsed with a tumor-associated antigen.

[1285] 1275. The method of aspect 1076, wherein the method further comprises administering a natural product-based therapeutic.

[1286] 1276. The method of aspect 1275, wherein the natural product-based therapeutic is derived from a plant source.Immorta-ANKC-PCT

[1287] 1277. The method of aspect 1276, wherein the plant source is selected from the group consisting of turmeric, green tea, and ginseng.

[1288] 1278. The method of aspect 1076, wherein the method further comprises administering a microbiome-modulating agent.

[1289] 1279. The method of aspect 1278, wherein the microbiome-modulating agent is a probiotic comprising at least one strain selected from the group consisting of Lactobacillus acidophilus and Bifidobacterium longum.

[1290] 1280. The method of aspect 1278, wherein the microbiome-modulating agent is a prebiotic selected from the group consisting of inulin, fructooligosaccharides (FOS), and galactooligosaccharides (GOS).

[1291] 1281. The method of aspect 1076, wherein the method further comprises administering a chemotherapeutic agent that enhances T cell priming.

[1292] 1282. The method of aspect 1281, wherein the chemotherapeutic agent is cyclophosphamide.

[1293] 1283. The method of aspect 1076, wherein the method further comprises administering a tumor microenvironment-modulating agent.

[1294] 1284. The method of aspect 1283, wherein the tumor microenvironmentmodulating agent targets at least one of hypoxia, acidosis, or extracellular matrix stiffness.

[1295] 1285. The method of aspect 1076, wherein the method further comprises administering an agent that enhances antigen presentation.

[1296] 1286. The method of aspect 1285, wherein the agent that enhances antigen presentation is a GM-CSF fusion protein.

[1297] 1287. The method of aspect 1076, wherein the method further comprises administering a tumor-specific peptide.

[1298] 1288. The method of aspect 1287, wherein the tumor-specific peptide is derived from a tumor-associated antigen selected from the group consisting of NY-ESO-1, WT1, and MAGE- A3.

[1299] 1289. The method of aspect 1076, wherein the method further comprises administering a tumor-specific RNA vaccine.

[1300] 1290. The method of aspect 1289, wherein the RNA vaccine encodes a tumor-associated antigen.

[1301] 1291. The method of aspect 1076, wherein the method further comprises administering a tumor-specific DNA vaccine.Immorta-ANKC-PCT

[1302] 1292. The method of aspect 1291, wherein the DNA vaccine encodes a tumor-associated antigen.

[1303] 1293. The method of aspect 1076, wherein the method further comprises administering a viral-based vaccine.

[1304] 1294. The method of aspect 1293, wherein the viral-based vaccine is an adenovirus-based vaccine.

[1305] 1295. The method of aspect 1076, wherein the method further comprises administering a peptide-MHC complex.

[1306] 1296. The method of aspect 1295, wherein the peptide-MHC complex targets a tumor-specific neoantigen.

[1307] 1297. The method of aspect 1076, wherein the method further comprises administering a tumor-specific antibody-drug conjugate.

[1308] 1298. The method of aspect 1297, wherein the antibody-drug conjugate targets a tumor-associated antigen.

[1309] 1299. The method of aspect 1076, wherein the method further comprises administering a tumor-specific radioconjugate.

[1310] 1300. The method of aspect 1299, wherein the radioconjugate uses an isotope selected from the group consisting of iodine-131 and yttrium-90.

[1311] 1301. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immunotoxin.

[1312] 1302. The method of aspect 1301, wherein the immunotoxin targets a tumor-associated antigen.

[1313] 1303. The method of aspect 1076, wherein the method further comprises administering a tumor-specific small molecule-drug conjugate.

[1314] 1304. The method of aspect 1303, wherein the small molecule-drug conjugate targets a tumor-associated pathway.

[1315] 1305. The method of aspect 1076, wherein the method further comprises administering a tumor-specific nanobody.

[1316] 1306. The method of aspect 1305, wherein the nanobody targets a tumor-associated antigen.

[1317] 1307. The method of aspect 1076, wherein the method further comprises administering a tumor-specific aptamer.

[1318] 1308. The method of aspect 1307, wherein the aptamer targets a tumor-associated antigen.Immorta-ANKC-PCT

[1319] 1309. The method of aspect 1076, wherein the method further comprises administering a tumor-specific peptide-drug conjugate.

[1320] 1310. The method of aspect 1309, wherein the peptide-drug conjugate targets a tumor-associated antigen.

[1321] 1311. The method of aspect 1076, wherein the method further comprises administering a tumor-specific oncolytic peptide.

[1322] 1312. The method of aspect 1311, wherein the oncolytic peptide induces tumor cell lysis.

[1323] 1313. The method of aspect 1076, wherein the method further comprises administering a tumor-specific small molecule inhibitor.

[1324] 1314. The method of aspect 1313, wherein the small molecule inhibitor targets a tumor-associated pathway selected from the group consisting of MAPK, JAK / STAT, and TGF-β.

[1325] 1315. The method of aspect 1076, wherein the method further comprises administering a tumor-specific protein kinase inhibitor.

[1326] 1316. The method of aspect 1315, wherein the protein kinase inhibitor targets at least one kinase selected from the group consisting of ALK, BTK, and KIT.

[1327] 1317. The method of aspect 1076, wherein the method further comprises administering a tumor-specific phosphatase inhibitor.

[1328] 1318. The method of aspect 1317, wherein the phosphatase inhibitor targets PTEN.

[1329] 1319. The method of aspect 1076, wherein the method further comprises administering a tumor-specific G-protein-coupled receptor (GPCR) modulator.

[1330] 1320. The method of aspect 1319, wherein the GPCR modulator targets at least one receptor selected from the group consisting of CXCR4 and CCR7.

[1331] 1321. The method of aspect 1076, wherein the method further comprises administering a tumor-specific ion channel modulator.

[1332] 1322. The method of aspect 1321, wherein the ion channel modulator targets a calcium channel.

[1333] 1323. The method of aspect 1076, wherein the method further comprises administering a tumor-specific transporter inhibitor.

[1334] 1324. The method of aspect 1323, wherein the transporter inhibitor targets a glucose transporter.Immorta-ANKC-PCT

[1335] 1325. The method of aspect 1076, wherein the method further comprises administering a tumor-specific nuclear receptor modulator.

[1336] 1326. The method of aspect 1325, wherein the nuclear receptor modulator targets at least one receptor selected from the group consisting of androgen receptor (AR) and estrogen receptor (ER).

[1337] 1327. The method of aspect 1076, wherein the method further comprises administering a tumor-specific transcription factor inhibitor.

[1338] 1328. The method of aspect 1327, wherein the transcription factor inhibitor targets at least one transcription factor selected from the group consisting of MYC, HIF-1α, and NF-κB.

[1339] 1329. The method of aspect 1076, wherein the method further comprises administering a tumor-specific epigenetic modulator.

[1340] 1330. The method of aspect 1329, wherein the epigenetic modulator targets at least one enzyme selected from the group consisting of EZH2 and DNMT1.

[1341] 1331. The method of aspect 1076, wherein the method further comprises administering a tumor-specific proteasome activator.

[1342] 1332. The method of aspect 1331, wherein the proteasome activator enhances antigen presentation.

[1343] 1333. The method of aspect 1076, wherein the method further comprises administering a tumor-specific autophagy modulator.

[1344] 1334. The method of aspect 1333, wherein the autophagy modulator inhibits autophagy.

[1345] 1335. The method of aspect 1076, wherein the method further comprises administering a tumor-specific apoptosis inducer.

[1346] 1336. The method of aspect 1335, wherein the apoptosis inducer is a BH3 mimetic.

[1347] 1337. The method of aspect 1076, wherein the method further comprises administering a tumor-specific necroptosis inducer.

[1348] 1338. The method of aspect 1337, wherein the necroptosis inducer targets RIPK1

[1349] 1339. The method of aspect 1076, wherein the method further comprises administering a tumor-specific ferroptosis inducer.

[1350] 1340. The method of aspect 1339, wherein the ferroptosis inducer targets GPX4.Immorta-ANKC-PCT

[1351] 1341. The method of aspect 1076, wherein the method further comprises administering a tumor-specific pyroptosis inducer.

[1352] 1342. The method of aspect 1341, wherein the pyroptosis inducer targets caspase- 1.

[1353] 1343. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-recruiting agent.

[1354] 1344. The method of aspect 1343, wherein the immune cell-recruiting agent is a chemokine selected from the group consisting of CCL5, CXCL9, and CXCL10.

[1355] 1345. The method of aspect 1076, wherein the method further comprises administering a tumor-specific cytokine fusion protein.

[1356] 1346. The method of aspect 1345, wherein the cytokine fusion protein includes IL-15.

[1357] 1347. The method of aspect 1076, wherein the method further comprises administering a tumor-specific bispecific T cell engager (BiTE).

[1358] 1348. The method of aspect 1347, wherein the BiTE targets CD3 and a tumor-associated antigen.

[1359] 1349. The method of aspect 1076, wherein the method further comprises administering a tumor-specific trispecific antibody.

[1360] 1350. The method of aspect 1349, wherein the trispecific antibody targets CD3, a tumor-associated antigen, and an NK cell receptor.

[1361] 1351. The method of aspect 1076, wherein the method further comprises administering a tumor-specific antibody-dependent cell-mediated cytotoxicity (ADCC) enhancer.

[1362] 1352. The method of aspect 1351, wherein the ADCC enhancer is an antiCD 16 antibody.

[1363] 1353. The method of aspect 1076, wherein the method further comprises administering a tumor-specific complement-dependent cytotoxicity (CDC) enhancer.

[1364] 1354. The method of aspect 1353, wherein the CDC enhancer is an antiCD 55 antibody.

[1365] 1355. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-editing agent.

[1366] 1356. The method of aspect 1355, wherein the immune cell-editing agent uses CRISPR to enhance T cell function.Immorta-ANKC-PCT

[1367] 1357. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-reprogramming agent.

[1368] 1358. The method of aspect 1357, wherein the immune cell -reprogramming agent converts M2 macrophages to Ml macrophages.

[1369] 1359. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-trafficking agent.

[1370] 1360. The method of aspect 1359, wherein the immune cell-trafficking agent enhances T cell homing to the tumor.

[1371] 1361. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-survival agent.

[1372] 1362. The method of aspect 1361, wherein the immune cell -survival agent is an anti-apoptotic protein.

[1373] 1363. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-proliferation agent.

[1374] 1364. The method of aspect 1363, wherein the immune cell-proliferation agent is a growth factor.

[1375] 1365. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-differentiation agent.

[1376] 1366. The method of aspect 1365, wherein the immune cell-differentiation agent promotes Thl differentiation.

[1377] 1367. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-activation agent.

[1378] 1368. The method of aspect 1367, wherein the immune cell-activation agent is a CD28 agonist.

[1379] 1369. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-exhaustion inhibitor.

[1380] 1370. The method of aspect 1369, wherein the immune cell-exhaustion inhibitor targets LAG-3.

[1381] 1371. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-senescence inhibitor.

[1382] 1372. The method of aspect 1371, wherein the immune cell-senescence inhibitor targets p16.

[1383] 1373. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-metabolism modulator.Immorta-ANKC-PCT

[1384] 1374. The method of aspect 1373, wherein the immune cell-metabolism modulator enhances T cell glycolysis.

[1385] 1375. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-signaling modulator.

[1386] 1376. The method of aspect 1375, wherein the immune cell-signaling modulator enhances TCR signaling.

[1387] 1377. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-adhesion modulator.

[1388] 1378. The method of aspect 1377, wherein the immune cell-adhesion modulator enhances T cell adhesion to tumor cells.

[1389] 1379. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-migration modulator.

[1390] 1380. The method of aspect 1379, wherein the immune cell-migration modulator enhances T cell migration to the tumor.

[1391] 1381. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-cytotoxicity enhancer.

[1392] 1382. The method of aspect 1381, wherein the immune cell-cytotoxicity enhancer increases perforin expression.

[1393] 1383. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-memory inducer.

[1394] 1384. The method of aspect 1383, wherein the immune cell-memory inducer promotes memory T cell formation.

[1395] 1385. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-stemness modulator.

[1396] 1386. The method of aspect 1385, wherein the immune cell-stemness modulator enhances T cell stemness.

[1397] 1387. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-plasticity modulator.

[1398] 1388. The method of aspect 1387, wherein the immune cell-plasticity modulator enhances T cell plasticity.

[1399] 1389. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-epigenetic modulator.

[1400] 1390. The method of aspect 1389, wherein the immune cell-epigenetic modulator enhances T cell effector function.Immorta-ANKC-PCT

[1401] 1391. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-transcriptional regulator.

[1402] 1392. The method of aspect 1391, wherein the immune cell-transcriptional regulator enhances T-bet expression.

[1403] 1393. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-post-translational modifier.

[1404] 1394. The method of aspect 1393, wherein the immune cell -post-translational modifier enhances T cell activation.

[1405] 1395. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein degradation modulator.

[1406] 1396. The method of aspect 1395, wherein the immune cell-protein degradation modulator enhances T cell function.

[1407] 1397. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein synthesis modulator.

[1408] 1398. The method of aspect 1397, wherein the immune cell-protein synthesis modulator enhances T cell cytokine production.

[1409] 1399. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-DNA repair modulator.

[1410] 1400. The method of aspect 1399, wherein the immune cell-DNA repair modulator enhances T cell survival.

[1411] 1401. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-RNA repair modulator.

[1412] 1402. The method of aspect 1401, wherein the immune cell-RNA repair modulator enhances T cell function.

[1413] 1403. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-lipid metabolism modulator.

[1414] 1404. The method of aspect 1403, wherein the immune cell-lipid metabolism modulator enhances T cell membrane fluidity.

[1415] 1405. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-glucose metabolism modulator.

[1416] 1406. The method of aspect 1405, wherein the immune cell-glucose metabolism modulator enhances T cell energy production.

[1417] 1407. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-amino acid metabolism modulator.Immorta-ANKC-PCT

[1418] 1408. The method of aspect 1407, wherein the immune cell-amino acid metabolism modulator enhances T cell proliferation.

[1419] 1409. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-nucleotide metabolism modulator.

[1420] 1410. The method of aspect 1409, wherein the immune cell-nucleotide metabolism modulator enhances T cell DNA synthesis.

[1421] 1411. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-mitochondrial function modulator.

[1422] 1412. The method of aspect 1411, wherein the immune cell-mitochondrial function modulator enhances T cell ATP production.

[1423] 1413. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-lysosomal function modulator.

[1424] 1414. The method of aspect 1413, wherein the immune cell-lysosomal function modulator enhances T cell antigen processing.

[1425] 1415. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-endoplasmic reticulum (ER) stress modulator.

[1426] 1416. The method of aspect 1415, wherein the immune cell-ER stress modulator enhances T cell protein folding.

[1427] 1417. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-Golgi apparatus function modulator.

[1428] 1418. The method of aspect 1417, wherein the immune cell-Golgi apparatus function modulator enhances T cell protein trafficking.

[1429] 1419. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-cytoskeletal modulator.

[1430] 1420. The method of aspect 1419, wherein the immune cell-cytoskeletal modulator enhances T cell migration.

[1431] 1421. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-nuclear transport modulator.

[1432] 1422. The method of aspect 1421, wherein the immune cell-nuclear transport modulator enhances T cell transcription factor activity.

[1433] 1423. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-chromatin remodeling modulator.Immorta-ANKC-PCT

[1434] 1424. The method of aspect 1423, wherein the immune cell-chromatin remodeling modulator enhances T cell gene expression.

[1435] 1425. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-histone modification modulator.

[1436] 1426. The method of aspect 1425, wherein the immune cell-histone modification modulator enhances T cell effector function.

[1437] 1427. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-DNA methylation modulator.

[1438] 1428. The method of aspect 1427, wherein the immune cell-DNA methylation modulator enhances T cell activation.

[1439] 1429. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-RNA methylation modulator.

[1440] 1430. The method of aspect 1429, wherein the immune cell-RNA methylation modulator enhances T cell mRNA stability.

[1441] 1431. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein methylation modulator.

[1442] 1432. The method of aspect 1431, wherein the immune cell-protein methylation modulator enhances T cell signaling.

[1443] 1433. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein acetylation modulator.

[1444] 1434. The method of aspect 1433, wherein the immune cell-protein acetylation modulator enhances T cell transcription.

[1445] 1435. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein phosphorylation modulator.

[1446] 1436. The method of aspect 1435, wherein the immune cell-protein phosphorylation modulator enhances T cell signaling.

[1447] 1437. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein ubiquitination modulator.

[1448] 1438. The method of aspect 1437, wherein the immune cell-protein ubiquitination modulator enhances T cell protein turnover.

[1449] 1439. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein sumoylation modulator.

[1450] 1440. The method of aspect 1439, wherein the immune cell-protein sumoylation modulator enhances T cell function.Immorta-ANKC-PCT

[1451] 1441. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein neddylation modulator.

[1452] 1442. The method of aspect 1441, wherein the immune cell-protein neddylation modulator enhances T cell survival.

[1453] 1443. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein glycosylation modulator.

[1454] 1444. The method of aspect 1443, wherein the immune cell-protein glycosylation modulator enhances T cell receptor stability.

[1455] 1445. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein lipidation modulator.

[1456] 1446. The method of aspect 1445, wherein the immune cell-protein lipidation modulator enhances T cell membrane localization.

[1457] 1447. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein prenylation modulator.

[1458] 1448. The method of aspect 1447, wherein the immune cell-protein prenylation modulator enhances T cell signaling.

[1459] 1449. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein myristoylation modulator.

[1460] 1450. The method of aspect 1449, wherein the immune cell-protein myristoylation modulator enhances T cell activation.

[1461] 1451. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein palmitoylation modulator.

[1462] 1452. The method of aspect 1451, wherein the immune cell-protein palmitoylation modulator enhances T cell function.

[1463] 1453. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein S-nitrosylation modulator.

[1464] 1454. The method of aspect 1453, wherein the immune cell-protein S-nitrosylation modulator enhances T cell survival.

[1465] 1455. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein carbonylation modulator.

[1466] 1456. The method of aspect 1455, wherein the immune cell-protein carbonylation modulator enhances T cell function.

[1467] 1457. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein sulfhydration modulator.Immorta-ANKC-PCT

[1468] 1458. The method of aspect 1457, wherein the immune cell-protein sulfhydration modulator enhances T cell signaling.

[1469] 1459. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein nitration modulator.

[1470] 1460. The method of aspect 1459, wherein the immune cell-protein nitration modulator enhances T cell activation.

[1471] 1461. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein oxidation modulator.

[1472] 1462. The method of aspect 1461, wherein the immune cell-protein oxidation modulator enhances T cell survival.

[1473] 1463. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein reduction modulator.

[1474] 1464. The method of aspect 1463, wherein the immune cell-protein reduction modulator enhances T cell function.

[1475] 1465. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein folding modulator.

[1476] 1466. The method of aspect 1465, wherein the immune cell-protein folding modulator enhances T cell protein stability.

[1477] 1467. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein trafficking modulator.

[1478] 1468. The method of aspect 1467, wherein the immune cell-protein trafficking modulator enhances T cell receptor expression.

[1479] 1469. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein secretion modulator.

[1480] 1470. The method of aspect 1469, wherein the immune cell-protein secretion modulator enhances T cell cytokine secretion.

[1481] 1471. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein degradation enhancer.

[1482] 1472. The method of aspect 1471, wherein the immune cell-protein degradation enhancer enhances T cell protein turnover.

[1483] 1473. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein synthesis enhancer.

[1484] 1474. The method of aspect 1473, wherein the immune cell-protein synthesis enhancer enhances T cell cytokine production.Immorta-ANKC-PCT

[1485] 1475. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-DNA repair enhancer.

[1486] 1476. The method of aspect 1475, wherein the immune cell-DNA repair enhancer enhances T cell survival.

[1487] 1477. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-RNA repair enhancer.

[1488] 1478. The method of aspect 1477, wherein the immune cell-RNA repair enhancer enhances T cell function.

[1489] 1479. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-lipid metabolism enhancer.

[1490] 1480. The method of aspect 1479, wherein the immune cell-lipid metabolism enhancer enhances T cell membrane fluidity.

[1491] 1481. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-glucose metabolism enhancer.

[1492] 1482. The method of aspect 1481, wherein the immune cell-glucose metabolism enhancer enhances T cell energy production.

[1493] 1483. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-amino acid metabolism enhancer.

[1494] 1484. The method of aspect 1483, wherein the immune cell-amino acid metabolism enhancer enhances T cell proliferation.

[1495] 1485. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-nucleotide metabolism enhancer.

[1496] 1486. The method of aspect 1485, wherein the immune cell-nucleotide metabolism enhancer enhances T cell DNA synthesis.

[1497] 1487. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-mitochondrial function enhancer.

[1498] 1488. The method of aspect 1487, wherein the immune cell-mitochondrial function enhancer enhances T cell ATP production.

[1499] 1489. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-lysosomal function enhancer.

[1500] 1490. The method of aspect 1489, wherein the immune cell-lysosomal function enhancer enhances T cell antigen processing.

[1501] 1491. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-ER stress reducer.Immorta-ANKC-PCT

[1502] 1492. The method of aspect 1491, wherein the immune cell-ER stress reducer enhances T cell protein folding.

[1503] 1493. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-Golgi apparatus function enhancer.

[1504] 1494. The method of aspect 1493, wherein the immune cell-Golgi apparatus function enhancer enhances T cell protein trafficking.

[1505] 1495. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-cytoskeletal enhancer.

[1506] 1496. The method of aspect 1495, wherein the immune cell-cytoskeletal enhancer enhances T cell migration.

[1507] 1497. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-nuclear transport enhancer.

[1508] 1498. The method of aspect 1497, wherein the immune cell-nuclear transport enhancer enhances T cell transcription factor activity.

[1509] 1499. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-chromatin remodeling enhancer.

[1510] 1500. The method of aspect 1499, wherein the immune cell-chromatin remodeling enhancer enhances T cell gene expression.

[1511] 1501. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-histone modification enhancer.

[1512] 1502. The method of aspect 1501, wherein the immune cell-histone modification enhancer enhances T cell effector function.

[1513] 1503. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-DNA methylation enhancer.

[1514] 1504. The method of aspect 1503, wherein the immune cell-DNA methylation enhancer enhances T cell activation.

[1515] 1505. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-RNA methylation enhancer.

[1516] 1506. The method of aspect 1505, wherein the immune cell-RNA methylation enhancer enhances T cell mRNA stability.

[1517] 1507. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein methylation enhancer.

[1518] 1508. The method of aspect 1507, wherein the immune cell-protein methylation enhancer enhances T cell signaling.Immorta-ANKC-PCT

[1519] 1509. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein acetylation enhancer.

[1520] 1510. The method of aspect 1509, wherein the immune cell-protein acetylation enhancer enhances T cell transcription.

[1521] 1511. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein phosphorylation enhancer.

[1522] 1512. The method of aspect 1511, wherein the immune cell-protein phosphorylation enhancer enhances T cell signaling.

[1523] 1513. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein ubiquitination enhancer.

[1524] 1514. The method of aspect 1513, wherein the immune cell-protein ubiquitination enhancer enhances T cell protein turnover.

[1525] 1515. The method of aspect 1076, wherein the method further comprises administering a tumor-specific immune cell-protein sumoylation enhancer.

[1526] 1516. The method of aspect 1515, wherein the immune cell is a CAR-T cell.

[1527] 1517. A method of stimulating antigen-specific T cell responses after vaccination with a tumor derived antigen comprising administration of one or more senolytic agents, one or more NK cell activators, and one or more tumor associated or tumor specific antigens.

[1528] 1518. The method of aspect 1517, wherein said tumor associated antigens are selected form a group comprising of: cancer-testis antigens (MAGE-A1, MAGE-A3, MAGE-A4, NY-ESO-1, SSX1, SSX2, LAGE-1, GAGE1, BAGE, CTAG2, PRAME, SCP1, XAGE1, DDX5, CAGE, CT45, CT47, SAGE1, HAGE, and PAGE5); differentiation antigens (Melan-A / MART-1, gplOO, Tyrosinase, PSA, PSMA, PAP, Mammaglobin-A, TRP-1, TRP-2, MC1R, CD19, CD20, CD22, CD30, CD33, CD38, CD138, Gp75, andPMEL); overexpressed antigens (HER2 / neu, EGFR, MUC1, Survivin, WT1, p53, hTERT, VEGF, cyclin Bl, c-Myc, EpCAM, EZH2, IDO1, MDM2, RhoC, BIRC5, TERT, KRAS, AKT1, and BCL-2); oncofetal antigens (CEA, AFP, 5T4, Hl 9, IGF2, GPC3, SALL4, and ONCOTROPHIN); tissue-specific antigens (Mesothelin, Claudin 18.2, LIV-1, CD44, CD70, CD123, CD171, ROR1, FOLR1, and MUC16); and glycolipid / glycoprotein antigens (GD2, GM2, Sialyl-Tn, Globo H, LeY, Fucosyl GM1, CA125, CA19-9, and CD133).

[1529] 1519. The method of aspect 1517, wherein the one or more senolytic agents are selected from the group consisting of dasatinib, quercetin, navitoclax, and fisetin.Immorta-ANKC-PCT

[1530] 1520. The method of aspect 1519, wherein the one or more senolytic agents include dasatinib.

[1531] 1521. The method of aspect 1519, wherein the one or more senolytic agents include quercetin.

[1532] 1522. The method of aspect 1519, wherein the one or more senolytic agents include navitoclax.

[1533] 1523. The method of aspect 1519, wherein the one or more senolytic agents include fisetin.

[1534] 1524. The method of aspect 1517, wherein the one or more NK cell activators are naturally occurring compounds.

[1535] 1525. The method of aspect 1524, wherein the naturally occurring compounds are selected from the group consisting of beta-glucans, arabinogalactans, fucoidans, curcumin, resveratrol, and epigallocatechin gallate (EGCG).

[1536] 1526. The method of aspect 1525, wherein the naturally occurring compound is a beta-glucan derived from a source selected from the group consisting of mushrooms, yeast, and oats.

[1537] 1527. The method of aspect 1526, wherein the beta-glucan is derived from a mushroom selected from the group consisting of reishi, shiitake, and maitake.

[1538] 1528. The method of aspect 1525, wherein the naturally occurring compound is curcumin.

[1539] 1529. The method of aspect 1525, wherein the naturally occurring compound is resveratrol.

[1540] 1530. The method of aspect 1525, wherein the naturally occurring compound is epigallocatechin gallate (EGCG).

[1541] 1531. The method of aspect 1517, wherein the one or more NK cell activators include a cytokine.

[1542] 1532. The method of aspect 1531, wherein the cytokine is selected from the group consisting of IL-2, IL- 15, IL- 18, and IL-21.

[1543] 1533. The method of aspect 1532, wherein the cytokine is IL-2.

[1544] 1534. The method of aspect 1532, wherein the cytokine is IL-15.

[1545] 1535. The method of aspect 1532, wherein the cytokine is IL-18.

[1546] 1536. The method of aspect 1532, wherein the cytokine is IL-21.

[1547] 1537. The method of aspect 1517, wherein the one or more NK cell activators include a monoclonal antibody.Immorta-ANKC-PCT

[1548] 1538. The method of aspect 1537, wherein the monoclonal antibody targets at least one NK cell-activating receptor selected from the group consisting of NKG2D, NKp46, and NKp30.

[1549] 1539. The method of aspect 1517, wherein the one or more NK cell activators increase NK cell cytotoxicity against tumor cells by at least 10% compared to NK cells not exposed to the activators.

[1550] 1540. The method of aspect 1517, wherein the one or more tumor-associated or tumor-specific antigens are tumor-associated antigens.

[1551] 1541. The method of aspect 1540, wherein the tumor-associated antigens are selected from the group consisting of HER2, MUC1, PSA, and CEA.

[1552] 1542. The method of aspect 1541, wherein the tumor-associated antigen is HER2.

[1553] 1543. The method of aspect 1541, wherein the tumor-associated antigen is MUC1.

[1554] 1544. The method of aspect 1541, wherein the tumor-associated antigen is PSA.

[1555] 1545. The method of aspect 1541, wherein the tumor-associated antigen is CEA.

[1556] 1546. The method of aspect 1517, wherein the one or more tumor-associated or tumor-specific antigens are tumor-specific antigens.

[1557] 1547. The method of aspect 1546, wherein the tumor-specific antigens are neoantigens derived from tumor-specific mutations.

[1558] 1548. The method of aspect 1547, wherein the neoantigens are identified by sequencing the tumor genome of the subject.

[1559] 1549. The method of aspect 1517, wherein the one or more tumor-associated or tumor-specific antigens are administered as part of a vaccine composition.

[1560] 1550. The method of aspect 1549, wherein the vaccine composition is a peptide-based vaccine.

[1561] 1551. The method of aspect 1549, wherein the vaccine composition is an RNA-based vaccine.

[1562] 1552. The method of aspect 1549, wherein the vaccine composition is a DNA-based vaccine.

[1563] 1553. The method of aspect 1549, wherein the vaccine composition is a viral vector-based vaccine.Immorta-ANKC-PCT

[1564] 1554. The method of aspect 1553, wherein the viral vector is an adenovirus.

[1565] 1555. The method of aspect 1549, wherein the vaccine composition further comprises an adjuvant.

[1566] 1556. The method of aspect 1555, wherein the adjuvant is selected from the group consisting of alum, MF59, and CpG oligodeoxynucleotides.

[1567] 1557. The method of aspect 1517, wherein the method stimulates CD8+ T cell responses specific to the tumor-derived antigen.

[1568] 1558. The method of aspect 1517, wherein the method stimulates CD4+ T cell responses specific to the tumor-derived antigen.

[1569] 1559. The method of aspect 1517, wherein the method increases the production of at least one antigen-specific T cell-derived cytokine selected from the group consisting of IFN-γ, TNF-a, and IL-2 by at least 10%.

[1570] 1560. The method of aspect 1517, wherein the method increases antigenspecific T cell infiltration into the tumor by at least 15%.

[1571] 1561. The method of aspect 1517, wherein the tumor is a solid tumor.

[1572] 1562. The method of aspect 1561, wherein the solid tumor is selected from the group consisting of breast cancer, lung cancer, pancreatic cancer, colorectal cancer, and melanoma.

[1573] 1563. The method of aspect 1562, wherein the solid tumor is breast cancer.

[1574] 1564. The method of aspect 1562, wherein the solid tumor is lung cancer.

[1575] 1565. The method of aspect 1562, wherein the solid tumor is pancreatic cancer.

[1576] 1566. The method of aspect 1562, wherein the solid tumor is colorectal cancer.

[1577] 1567. The method of aspect 1562, wherein the solid tumor is melanoma.

[1578] 1568. The method of aspect 1517, wherein the tumor is a hematologic malignancy.

[1579] 1569. The method of aspect 1568, wherein the hematologic malignancy is selected from the group consisting of leukemia, lymphoma, and multiple myeloma.

[1580] 1570. The method of aspect 1569, wherein the hematologic malignancy is leukemia.

[1581] 1571. The method of aspect 1569, wherein the hematologic malignancy is lymphoma.Immorta-ANKC-PCT

[1582] 1572. The method of aspect 1569, wherein the hematologic malignancy is multiple myeloma.

[1583] 1573. The method of aspect 1517, wherein the one or more senolytic agents, the one or more NK cell activators, and the one or more tumor-associated or tumorspecific antigens are administered simultaneously.

[1584] 1574. The method of aspect 1517, wherein the one or more senolytic agents, the one or more NK cell activators, and the one or more tumor-associated or tumorspecific antigens are administered sequentially.

[1585] 1575. The method of aspect 1574, wherein the one or more senolytic agents are administered prior to the one or more NK cell activators and the one or more tumor-associated or tumor-specific antigens.

[1586] 1576. The method of aspect 1574, wherein the one or more tumor-associated or tumor-specific antigens are administered prior to the one or more senolytic agents and the one or more NK cell activators.

[1587] 1577. The method of aspect 1517, wherein the one or more senolytic agents are administered at a dose ranging from 0.1 mg / kg to 100 mg / kg of the subject’s body weight.

[1588] 1578. The method of aspect 1517, wherein the one or more NK cell activators are administered at a dose ranging from 0.5 mg / kg to 200 mg / kg of the subject’s body weight.

[1589] 1579. The method of aspect 1517, wherein the one or more tumor-associated or tumor-specific antigens are administered at a dose ranging from 0.01 mg to 10 mg per administration.

[1590] 1580. The method of aspect 1517, wherein the one or more senolytic agents are administered orally.

[1591] 1581. The method of aspect 1517, wherein the one or more NK cell activators are administered intravenously.

[1592] 1582. The method of aspect 1517, wherein the one or more tumor-associated or tumor-specific antigens are administered intradermally.

[1593] 1583. The method of aspect 1517, wherein the one or more senolytic agents, the one or more NK cell activators, and the one or more tumor-associated or tumorspecific antigens are administered as part of a single pharmaceutical composition.

[1594] 1584. The method of aspect 1583, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier.Immorta-ANKC-PCT

[1595] 1585. The method of aspect 1517, wherein the one or more senolytic agents, the one or more NK cell activators, and the one or more tumor-associated or tumorspecific antigens are administered as separate pharmaceutical compositions.

[1596] 1586. The method of aspect 1517, wherein the administration occurs daily for a period of at least one week.

[1597] 1587. The method of aspect 1517, wherein the administration occurs weekly for a period of at least one month.

[1598] 1588. The method of aspect 1517, wherein the subject is a human.

[1599] 1589. The method of aspect 1517, wherein the subject is a non-human mammal.

[1600] 1590. The method of aspect 1517, further comprising administering an additional therapeutic agent.

[1601] 1591. The method of aspect 1590, wherein the additional therapeutic agent is an immune checkpoint inhibitor.

[1602] 1592. The method of aspect 1591, wherein the immune checkpoint inhibitor targets at least one of PD-1, PD-L1, or CT.

[1603] 1593. A method of reducing cancer metastasis comprising administration of exogenous NK cells and / or activation of endogenous NK cells in the presence of one or more antioxidants, and / or one or more polyphenols, and / or one or more COX inhibitors, and / or one or more senolytic agents, optionally administering immunogenic tumor associated peptides.

[1604] 1594. The method of aspect 1593, wherein the exogenous NK cells are administered.

[1605] 1595. The method of aspect 1594, wherein the exogenous NK cells are autologous.

[1606] 1596. The method of aspect 1594, wherein the exogenous NK cells are allogeneic.

[1607] 1597. The method of aspect 1596, wherein the allogeneic NK cells are derived from a healthy donor.

[1608] 1598. The method of aspect 1596, wherein the allogeneic NK cells are derived from an induced pluripotent stem cell (iPSC) source.

[1609] 1599. The method of aspect 1594, wherein the exogenous NK cells are genetically modified.Immorta-ANKC-PCT

[1610] 1600. The method of aspect 1599, wherein the exogenous NK cells are modified to express a chimeric antigen receptor (CAR).

[1611] 1601. The method of aspect 1600, wherein the CAR targets a tumor-associated antigen selected from the group consisting of CD 19, HER2, and EGFR.

[1612] 1602. The method of aspect 1599, wherein the exogenous NK cells are modified to overexpress at least one NK cell-activating receptor selected from the group consisting of NKG2D, NKp46, and NKp30.

[1613] 1603. The method of aspect 1594, wherein the exogenous NK cells are expanded ex vivo prior to administration.

[1614] 1604. The method of aspect 1603, wherein the ex vivo expansion includes culturing the NK cells in the presence of at least one cytokine selected from the group consisting of IL-2, IL- 15, and IL-21.

[1615] 1605. The method of aspect 1594, wherein the exogenous NK cells are administered at a dose ranging from 1 x 106to 1 x 109cells per kg of the subject’s body weight.

[1616] 1606. The method of aspect 1593, wherein the endogenous NK cells are activated.

[1617] 1607. The method of aspect 1606, wherein activating endogenous NK cells comprises administering one or more NK cell-activating agents.

[1618] 1608. The method of aspect 1607, wherein the one or more NK cellactivating agents are naturally occurring compounds.

[1619] 1609. The method of aspect 1608, wherein the naturally occurring compounds are selected from the group consisting of beta-glucans, arabinogalactans, fucoidans, curcumin, resveratrol, and epigallocatechin gallate (EGCG).

[1620] 1610. The method of aspect 1609, wherein the naturally occurring compound is a beta-glucan derived from a source selected from the group consisting of mushrooms, yeast, and oats.

[1621] 1611. The method of aspect 1610, wherein the beta-glucan is derived from a mushroom selected from the group consisting of reishi, shiitake, and maitake.

[1622] 1612. The method of aspect 1609, wherein the naturally occurring compound is curcumin.

[1623] 1613. The method of aspect 1609, wherein the naturally occurring compound is resveratrol.Immorta-ANKC-PCT

[1624] 1614. The method of aspect 1609, wherein the naturally occurring compound is epigallocatechin gallate (EGCG).

[1625] 1615. The method of aspect 1607, wherein the one or more NK cellactivating agents include a cytokine.

[1626] 1616. The method of aspect 1615, wherein the cytokine is selected from the group consisting of IL-2, IL- 15, IL- 18, and IL-21.

[1627] 1617. The method of aspect 1616, wherein the cytokine is IL-2.

[1628] 1618. The method of aspect 1616, wherein the cytokine is IL-15.

[1629] 1619. The method of aspect 1616, wherein the cytokine is IL-18.

[1630] 1620. The method of aspect 1616, wherein the cytokine is IL-21.

[1631] 1621. The method of aspect 1607, wherein the one or more NK cellactivating agents include a monoclonal antibody.

[1632] 1622. The method of aspect 1621, wherein the monoclonal antibody targets at least one NK cell-activating receptor selected from the group consisting of NKG2D, NKp46, and NKp30.

[1633] 1623. The method of aspect 1606, wherein activating endogenous NK cells increases NK cell cytotoxicity against metastatic tumor cells by at least 10% compared to NK cells not activated.

[1634] 1624. The method of aspect 1593, wherein the one or more antioxidants are administered.

[1635] 1625. The method of aspect 1624, wherein the one or more antioxidants are selected from the group consisting of N-acetylcysteine, glutathione, coenzyme Q10, vitamin C, vitamin E, and alpha-lipoic acid.

[1636] 1626. The method of aspect 1625, wherein the antioxidant is N-acetylcysteine.

[1637] 1627. The method of aspect 1625, wherein the antioxidant is glutathione.

[1638] 1628. The method of aspect 1625, wherein the antioxidant is coenzyme Q10.

[1639] 1629. The method of aspect 1625, wherein the antioxidant is vitamin C.

[1640] 1630. The method of aspect 1625, wherein the antioxidant is vitamin E.

[1641] 1631. The method of aspect 1625, wherein the antioxidant is alpha-lipoic acid.

[1642] 1632. The method of aspect 1624, wherein the one or more antioxidants are administered at a dose ranging from 1 mg / kg to 500 mg / kg of the subject’s body weight.Immorta-ANKC-PCT

[1643] 1633. The method of aspect 1593, wherein the one or more polyphenols are administered.

[1644] 1634. The method of aspect 1633, wherein the one or more polyphenols are selected from the group consisting of curcumin, resveratrol, epigallocatechin gallate (EGCG), quercetin, and genistein.

[1645] 1635. The method of aspect 1634, wherein the polyphenol is curcumin.

[1646] 1636. The method of aspect 1634, wherein the polyphenol is resveratrol.

[1647] 1637. The method of aspect 1634, wherein the polyphenol is epigallocatechin gallate (EGCG).

[1648] 1638. The method of aspect 1634, wherein the polyphenol is quercetin.

[1649] 1639. The method of aspect 1634, wherein the polyphenol is genistein.

[1650] 1640. The method of aspect 1633, wherein the one or more polyphenols are administered at a dose ranging from 0.5 mg / kg to 200 mg / kg of the subject’s body weight.

[1651] 1641. The method of aspect 1593, wherein the one or more COX inhibitors are administered.

[1652] 1642. The method of aspect 1641, wherein the one or more COX inhibitors are selected from the group consisting of aspirin, ibuprofen, celecoxib, and naproxen.

[1653] 1643. The method of aspect 1642, wherein the COX inhibitor is aspirin.

[1654] 1644. The method of aspect 1642, wherein the COX inhibitor is ibuprofen.

[1655] 1645. The method of aspect 1642, wherein the COX inhibitor is celecoxib.

[1656] 1646. The method of aspect 1642, wherein the COX inhibitor is naproxen.

[1657] 1647. The method of aspect 1641, wherein the one or more COX inhibitors are administered at a dose ranging from 0.1 mg / kg to 50 mg / kg of the subject’s body weight.

[1658] 1648. The method of aspect 1593, wherein the one or more senolytic agents are administered.

[1659] 1649. The method of aspect 1648, wherein the one or more senolytic agents are selected from the group consisting of dasatinib, quercetin, navitoclax, and fisetin.

[1660] 1650. The method of aspect 1649, wherein the one or more senolytic agents include dasatinib.

[1661] 1651. The method of aspect 1649, wherein the one or more senolytic agents include quercetin.Immorta-ANKC-PCT

[1662] 1652. The method of aspect 1649, wherein the one or more senolytic agents include navitoclax.

[1663] 1653. The method of aspect 1649, wherein the one or more senolytic agents include fisetin.

[1664] 1654. The method of aspect 1648, wherein the one or more senolytic agents are administered at a dose ranging from 0.1 mg / kg to 100 mg / kg of the subject’s body weight.

[1665] 1655. The method of aspect 1593, wherein the one or more immunogenic tumor-associated peptides are administered.

[1666] 1656. The method of aspect 1655, wherein the one or more immunogenic tumor-associated peptides are selected from the group consisting of peptides derived from HER2, MUC1, PSA, and CEA.

[1667] 1657. The method of aspect 1656, wherein the immunogenic tumor-associated peptide is derived from HER2.

[1668] 1658. The method of aspect 1656, wherein the immunogenic tumor-associated peptide is derived from MUC1.

[1669] 1659. The method of aspect 1656, wherein the immunogenic tumor-associated peptide is derived from PSA.

[1670] 1660. The method of aspect 1656, wherein the immunogenic tumor-associated peptide is derived from CEA.

[1671] 1661. The method of aspect 1655, wherein the one or more immunogenic tumor-associated peptides are administered at a dose ranging from 0.01 mg to 10 mg per administration.

[1672] 1662. The method of aspect 1655, wherein the one or more immunogenic tumor-associated peptides are administered as part of a vaccine composition.

[1673] 1663. The method of aspect 1662, wherein the vaccine composition further comprises an adjuvant.

[1674] 1664. The method of aspect 1663, wherein the adjuvant is selected from the group consisting of alum, MF59, and CpG oligodeoxynucleotides.

[1675] 1665. The method of aspect 1593, wherein the cancer is a solid tumor.

[1676] 1666. The method of aspect 1665, wherein the solid tumor is selected from the group consisting of breast cancer, lung cancer, pancreatic cancer, colorectal cancer, and melanoma.

[1677] 1667. The method of aspect 1666, wherein the solid tumor is breast cancer.Immorta-ANKC-PCT

[1678] 1668. The method of aspect 1666, wherein the solid tumor is lung cancer.

[1679] 1669. The method of aspect 1666, wherein the solid tumor is pancreatic cancer.

[1680] 1670. The method of aspect 1666, wherein the solid tumor is colorectal cancer.

[1681] 1671. The method of aspect 1666, wherein the solid tumor is melanoma.

[1682] 1672. The method of aspect 1593, wherein the cancer is a hematologic malignancy.

[1683] 1673. The method of aspect 1672, wherein the hematologic malignancy is selected from the group consisting of leukemia, lymphoma, and multiple myeloma.

[1684] 1674. The method of aspect 1673, wherein the hematologic malignancy is leukemia.

[1685] 1675. The method of aspect 1673, wherein the hematologic malignancy is lymphoma.

[1686] 1676. The method of aspect 1673, wherein the hematologic malignancy is multiple myeloma.

[1687] 1677. The method of aspect 1593, wherein the administration of the exogenous NK cells and / or activation of endogenous NK cells and the administration of the one or more antioxidants, polyphenols, COX inhibitors, and / or senolytic agents are performed simultaneously.

[1688] 1678. The method of aspect 1593, wherein the administration of the exogenous NK cells and / or activation of endogenous NK cells and the administration of the one or more antioxidants, polyphenols, COX inhibitors, and / or senolytic agents are performed sequentially.

[1689] 1679. The method of aspect 1678, wherein the exogenous NK cells and / or activation of endogenous NK cells are performed prior to the administration of the one or more antioxidants, polyphenols, COX inhibitors, and / or senolytic agents.

[1690] 1680. The method of aspect 1678, wherein the one or more antioxidants, polyphenols, COX inhibitors, and / or senolytic agents are administered prior to the exogenous NK cells and / or activation of endogenous NK cells.

[1691] 1681. The method of aspect 1593, wherein the exogenous NK cells are administered intravenously.

[1692] 1682. The method of aspect 1593, wherein the one or more antioxidants are administered orally.Immorta-ANKC-PCT

[1693] 1683. The method of aspect 1593, wherein the one or more polyphenols are administered orally.

[1694] 1684. The method of aspect 1593, wherein the one or more COX inhibitors are administered orally.

[1695] 1685. The method of aspect 1593, wherein the one or more senolytic agents are administered orally.

[1696] 1686. The method of aspect 1593, wherein the one or more immunogenic tumor-associated peptides are administered intradermally.

[1697] 1687. The method of aspect 1593, wherein the administration occurs daily for a period of at least one week.

[1698] 1688. The method of aspect 1593, wherein the administration occurs weekly for a period of at least one month.

[1699] 1689. The method of aspect 1593, wherein the subject is a human.

[1700] 1690. The method of aspect 1593, wherein the subject is a non-human mammal.

[1701] 1691. The method of aspect 1593, further comprising administering an additional therapeutic agent.

[1702] 1692. The method of aspect 1691, wherein the additional therapeutic agent is an immune checkpoint inhibitor.

[1703] 1693. The method of aspect 1692, wherein the immune checkpoint inhibitor targets at least one of PD-1, PD-L1, or CTLA-4.

[1704] 1694. The method of aspect 1693, wherein the immune checkpoint inhibitor is selected from the group consisting of pembrolizumab, nivolumab, and ipilimumab.

[1705] 1695. The method of aspect 1691, wherein the additional therapeutic agent is a chemotherapeutic agent.

[1706] 1696. The method of aspect 1695, wherein the chemotherapeutic agent is selected from the group consisting of paclitaxel, doxorubicin, and cisplatin.

[1707] 1697. The method of aspect 1593, further comprising monitoring the subject for a reduction in metastatic tumor burden.

[1708] 1698. The method of aspect 1593, further comprising monitoring the subject for an increase in NK cell activity.

[1709] 1699. The method of aspect 1593, wherein the method reduces the number of metastatic lesions by at least 10% compared to a control group not receiving the combination.Immorta-ANKC-PCT

[1710] 1700. The method of aspect 1593, wherein the method increases the subject’s progression-free survival by at least 10% compared to treatment without the combination.

[1711] 1701. The method of aspect 1593, wherein the method increases the subject’s overall survival by at least 10% compared to treatment without the combination.

[1712] 1702. The method of aspect 1593, wherein the cancer is metastatic.

[1713] 1703. The method of aspect 1593, wherein the cancer is refractory to at least one prior therapy.

[1714] 1704. The method of aspect 1593, wherein the one or more senolytic agents target at least one pathway selected from the group consisting of Bcl-2, PI3K / AKT, and p53.

[1715] 1705. The method of aspect 1593, wherein the method reduces the number of senescent cells in the tumor microenvironment by at least 20%.

[1716] 1706. The method of aspect 1593, wherein the method increases NK cell infiltration into metastatic sites by at least 15%.

[1717] 1707. The method of aspect 1593, wherein the one or more antioxidants are administered in a liposomal formulation.

[1718] 1708. The method of aspect 1593, wherein the one or more polyphenols are administered in a nanoparticle formulation.

[1719] 1709. The method of aspect 1593, wherein the one or more COX inhibitors are administered in a sustained-release formulation.

[1720] 1710. The method of aspect 1593, wherein the one or more senolytic agents are administered in a nanoparticle formulation.

[1721] 1711. The method of aspect 1593, wherein the exogenous NK cells are cryopreserved prior to administration.

[1722] 1712. The method of aspect 1593, wherein the method further comprises a step of identifying the subject as having a cancer with high senescent cell burden prior to administration.

[1723] 1713. The method of aspect 1712, wherein the senescent cell burden is determined by measuring the expression of at least one senescence marker selected from the group consisting of p16, p21, and SA-β-gal.

[1724] 1714. The method of aspect 1593, wherein the method further comprises a step of identifying the subject as having low NK cell activity prior to administration.Immorta-ANKC-PCT

[1725] 1715. The method of aspect 1714, wherein the NK cell activity is determined by measuring the expression of at least one NK cell activation marker selected from the group consisting of CD69 and CD107a.

[1726] 1716. The method of aspect 1593, wherein the method further comprises a step of identifying the subject as having a high risk of metastasis prior to administration.

[1727] 1717. The method of aspect 1716, wherein the risk of metastasis is determined by imaging techniques selected from the group consisting of MRI, CT scan, and PET scan.

[1728] 1718. The method of aspect 1593, wherein the one or more antioxidants have a purity of at least 90%.

[1729] 1719. The method of aspect 1593, wherein the one or more polyphenols have a purity of at least 90%.

[1730] 1720. The method of aspect 1593, wherein the one or more COX inhibitors have a purity of at least 90%.

[1731] 1721. The method of aspect 1593, wherein the one or more senolytic agents have a purity of at least 90%.

[1732] 1722. The method of aspect 1593, wherein the method further comprises administering a dietary supplement to the subject.

[1733] 1723. The method of aspect 1722, wherein the dietary supplement comprises at least one vitamin selected from the group consisting of vitamin C and vitamin D.

[1734] 1724. The method of aspect 1593, wherein the method further comprises subjecting the subject to radiation therapy.

[1735] 1725. The method of aspect 1593, wherein the method further comprises surgically resecting a primary tumor from the subject prior to administration.

[1736] 1726. The method of aspect 1593, wherein the method is used as an adjuvant therapy following a primary cancer treatment.

[1737] 1727. The method of aspect 1593, wherein the method is used as a neoadjuvant therapy prior to a primary cancer treatment.

[1738] 1728. The method of aspect 1593, wherein the method reduces cancer recurrence rates by at least 10% compared to a control group not receiving the combination.

[1739] 1729. The method of aspect 1593, wherein the method is performed in combination with a ketogenic diet.Immorta-ANKC-PCT

[1740] 1730. The method of aspect 1593, wherein the method further comprises administering an agent capable of reducing T regulatory cell number and / or activity.

[1741] 1731. The method of aspect 1730, wherein the agent capable of reducing T regulatory cell number and / or activity is selected from the group consisting of cyclophosphamide, ipilimumab, and pembrolizumab.

[1742] 1732. The method of aspect 1593, wherein the method further comprises administering an agent that suppresses myeloid-derived suppressor cell (MDSC) number and / or function.

[1743] 1733. The method of aspect 1732, wherein the agent that suppresses MDSC number and / or function is selected from the group consisting of all-trans retinoic acid (ATRA), sildenafil, and gemcitabine.

[1744] 1734. The method of aspect 1593, wherein the method further comprises administering a microbiome metabolite.

[1745] 1735. The method of aspect 1734, wherein the microbiome metabolite is a short-chain fatty acid selected from the group consisting of butyrate, propionate, and acetate.

[1746] 1736. The method of aspect 1593, wherein the method further comprises administering an agent that activates memory NK cells.

[1747] 1737. The method of aspect 1736, wherein the agent that activates memory NK cells is a cytokine selected from the group consisting of IL- 12, IL- 15, and IL- 18.

[1748] 1738. The method of aspect 1593, wherein the method further comprises administering a tumor-specific antigen vaccine.

[1749] 1739. The method of aspect 1738, wherein the tumor-specific antigen vaccine comprises a neoantigen identified by sequencing the tumor genome of the subject.

[1750] 1740. The method of aspect 1593, wherein the method further comprises administering an anti-inflammatory agent.

[1751] 1741. The method of aspect 1740, wherein the anti-inflammatory agent is selected from the group consisting of aspirin, ibuprofen, and celecoxib.

[1752] 1742. The method of aspect 1593, wherein the method further comprises administering a CAR-T cell therapy.

[1753] 1743. The method of aspect 1593, wherein the method further comprises administering an oncolytic virus.Immorta-ANKC-PCT

[1754] 1744. The method of aspect 1743, wherein the oncolytic virus is selected from the group consisting of talimogene laherparepvec, reovirus, and vaccinia virus.

[1755] 1745. The method of aspect 1593, wherein the method further comprises administering a histone deacetylase (HDAC) inhibitor.

[1756] 1746. The method of aspect 1745, wherein the HDAC inhibitor is selected from the group consisting of vorinostat, romidepsin, and panobinostat.

[1757] 1747. The method of aspect 1593, wherein the method further comprises administering a DNA methyltransferase inhibitor.

[1758] 1748. The method of aspect 1747, wherein the DNA methyltransferase inhibitor is selected from the group consisting of azacitidine and decitabine.

[1759] 1749. The method of aspect 1593, wherein the method further comprises administering a tyrosine kinase inhibitor.

[1760] 1750. The method of aspect 1749, wherein the tyrosine kinase inhibitor is selected from the group consisting of erlotinib, gefitinib, and osimertinib.

[1761] 1751. The method of aspect 1593, wherein the method further comprises administering a proteasome inhibitor.

[1762] 1752. The method of aspect 1751, wherein the proteasome inhibitor is selected from the group consisting of bortezomib, carfilzomib, and ixazomib.

[1763] 1753. The method of aspect 1593, wherein the method further comprises administering a PARP inhibitor.

[1764] 1754. The method of aspect 1753, wherein the PARP inhibitor is selected from the group consisting of olaparib, rucaparib, and niraparib.

[1765] 1755. The method of aspect 1593, wherein the method further comprises administering a BCL-2 inhibitor.

[1766] 1756. The method of aspect 1755, wherein the BCL-2 inhibitor is venetoclax.

[1767] 1757. The method of aspect 1593, wherein the method further comprises administering an mTOR inhibitor.

[1768] 1758. The method of aspect 1757, wherein the mTOR inhibitor is selected from the group consisting of rapamycin, everolimus, and temsirolimus.

[1769] 1759. The method of aspect 1593, wherein the method further comprises administering a PI3K inhibitor.

[1770] 1760. The method of aspect 1759, wherein the PI3K inhibitor is selected from the group consisting of idelalisib, copanlisib, and duvelisib.Immorta-ANKC-PCT

[1771] 1761. The method of aspect 1593, wherein the method further comprises administering a CDK4 / 6 inhibitor.

[1772] 1762. The method of aspect 1761, wherein the CDK4 / 6 inhibitor is selected from the group consisting of palbociclib, ribociclib, and abemaciclib.

[1773] 1763. The method of aspect 1593, wherein the method further comprises administering an anti -angiogenic agent.

[1774] 1764. The method of aspect 1763, wherein the anti -angiogenic agent is selected from the group consisting of bevacizumab, sorafenib, and lenvatinib.

[1775] 1765. The method of aspect 1593, wherein the method further comprises administering a bispecific antibody.

[1776] 1766. The method of aspect 1765, wherein the bispecific antibody targets at least one of CD3 and a tumor-associated antigen.

[1777] 1767. The method of aspect 1593, wherein the method further comprises administering an adoptive cell therapy.

[1778] 1768. The method of aspect 1767, wherein the adoptive cell therapy comprises T cells.

[1779] 1769. The method of aspect 1593, wherein the method further comprises administering a tumor necrosis factor (TNF) superfamily agonist.

[1780] 1770. The method of aspect 1769, wherein the TNF superfamily agonist is a GITR agonist.

[1781] 1771. The method of aspect 1593, wherein the method further comprises administering a toll-like receptor (TLR) agonist.

[1782] 1772. The method of aspect 1771, wherein the TLR agonist is selected from the group consisting of imiquimod, resiquimod, and CpG oligodeoxynucleotides.

[1783] 1773. The method of aspect 1593, wherein the method further comprises administering a STING agonist.

[1784] 1774. The method of aspect 1773, wherein the STING agonist is a cyclic dinucleotide.

[1785] 1775. The method of aspect 1593, wherein the method further comprises administering a chemotherapeutic agent that induces immunogenic cell death.

[1786] 1776. The method of aspect 1775, wherein the chemotherapeutic agent is selected from the group consisting of anthracyclines, oxaliplatin, and cyclophosphamide.

[1787] 1777. The method of aspect 1593, wherein the method further comprises administering a radiotherapy sensitizer.Immorta-ANKC-PCT

[1788] 1778. The method of aspect 1777, wherein the radiotherapy sensitizer is a PARP inhibitor.

[1789] 1779. The method of aspect 1593, wherein the method further comprises administering a hypoxia-targeting agent.

[1790] 1780. The method of aspect 1779, wherein the hypoxia-targeting agent is tirapazamine.

[1791] 1781. The method of aspect 1593, wherein the method further comprises administering a cancer stem cell-targeting agent.

[1792] 1782. The method of aspect 1781, wherein the cancer stem cell-targeting agent targets at least one pathway selected from the group consisting of Wnt, Notch, and Hedgehog.

[1793] 1783. The method of aspect 1593, wherein the method further comprises administering a metabolic inhibitor.

[1794] 1784. The method of aspect 1783, wherein the metabolic inhibitor targets at least one of glycolysis, glutaminolysis, or fatty acid synthesis.

[1795] 1785. The method of aspect 1593, wherein the method further comprises administering an immune adjuvant.

[1796] 1786. The method of aspect 1785, wherein the immune adjuvant is selected from the group consisting of alum, MF59, and AS03.

[1797] 1787. The method of aspect 1593, wherein the method further comprises administering a peptide-based therapeutic.

[1798] 1788. The method of aspect 1787, wherein the peptide-based therapeutic targets a tumor-associated antigen.

[1799] 1789. The method of aspect 1593, wherein the method further comprises administering a small interfering RNA (siRNA).

[1800] 1790. The method of aspect 1789, wherein the siRNA targets a gene associated with tumor cell survival.

[1801] 1791. The method of aspect 1790, wherein the gene is selected from the group consisting of MYC, KRAS, and EGFR.

[1802] 1792. The method of aspect 1593, wherein the method further comprises administering a CRISPR-based therapeutic.

[1803] 1793. The method of aspect 1792, wherein the CRISPR-based therapeutic targets a gene associated with tumor cell survival.Immorta-ANKC-PCT

[1804] 1794. The method of aspect 1793, wherein the gene is selected from the group consisting of MYC, KRAS, and EGFR.

[1805] 1795. The method of aspect 1593, wherein the method further comprises administering a nanoparticle-based therapeutic.

[1806] 1796. The method of aspect 1795, wherein the nanoparticle-based therapeutic delivers the one or more antioxidants.

[1807] 1797. The method of aspect 1593, wherein the method further comprises administering a photodynamic therapy agent.

[1808] 1798. The method of aspect 1797, wherein the photodynamic therapy agent is a porphyrin derivative.

[1809] 1799. The method of aspect 1593, wherein the method further comprises administering a radiofrequency ablation therapy.

[1810] 1800. The method of aspect 1593, wherein the method further comprises administering a cryoablation therapy.

[1811] 1801. The method of aspect 1593, wherein the method further comprises administering a high-intensity focused ultrasound (HIFU) therapy.

[1812] 1802. The method of aspect 1593, wherein the method further comprises administering a laser interstitial thermal therapy (LITT).

[1813] 1803. The method of aspect 1593, wherein the method further comprises administering a targeted alpha therapy.

[1814] 1804. The method of aspect 1803, wherein the targeted alpha therapy uses an isotope selected from the group consisting of actinium-225 and bismuth-213.

[1815] 1805. The method of aspect 1593, wherein the method further comprises administering a boron neutron capture therapy (BNCT).

[1816] 1806. The method of aspect 1593, wherein the method further comprises administering a proton therapy.

[1817] 1807. The method of aspect 1593, wherein the method further comprises administering a carbon ion therapy.

[1818] 1808. The method of aspect 1593, wherein the method further comprises administering a stereotactic radiosurgery.

[1819] 1809. The method of aspect 1593, wherein the method further comprises administering a brachytherapy.

[1820] 1810. The method of aspect 1593, wherein the method further comprises administering a gene therapy.Immorta-ANKC-PCT

[1821] 1811. The method of aspect 1810, wherein the gene therapy introduces a gene encoding a cytokine that enhances anti-tumor immunity.

[1822] 1812. The method of aspect 1811, wherein the cytokine is selected from the group consisting of IL-12, GM-CSF, and IFN-γ.

[1823] 1813. The method of aspect 1593, wherein the method further comprises administering a viral vector-based therapy.

[1824] 1814. The method of aspect 1813, wherein the viral vector is an adeno-associated virus (AAV).

[1825] 1815. The method of aspect 1593, wherein the method further comprises administering a lipid nanoparticle-based therapy.

[1826] 1816. The method of aspect 1815, wherein the lipid nanoparticle delivers an mRNA encoding an immune-stimulatory protein.

[1827] 1817. The method of aspect 1593, wherein the method further comprises administering a dendritic cell-based therapy.

[1828] 1818. The method of aspect 1817, wherein the dendritic cell-based therapy involves dendritic cells pulsed with a tumor-associated antigen.

[1829] 1819. The method of aspect 1593, wherein the method further comprises administering a natural product-based therapeutic.

[1830] 1820. The method of aspect 1819, wherein the natural product-based therapeutic is derived from a plant source.

[1831] 1821. The method of aspect 1820, wherein the plant source is selected from the group consisting of turmeric, green tea, and ginseng.

[1832] 1822. The method of aspect 1593, wherein the method further comprises administering a microbiome-modulating agent.

[1833] 1823. The method of aspect 1822, wherein the microbiome-modulating agent is a probiotic comprising at least one strain selected from the group consisting of Lactobacillus acidophilus and Bifidobacterium longum.

[1834] 1824. The method of aspect 1822, wherein the microbiome-modulating agent is a prebiotic selected from the group consisting of inulin, fructooligosaccharides (FOS), and galactooligosaccharides (GOS).

[1835] 1825. The method of aspect 1593, wherein the method further comprises administering a chemotherapeutic agent that enhances T cell priming.

[1836] 1826. The method of aspect 1825, wherein the chemotherapeutic agent is cyclophosphamide.Immorta-ANKC-PCT

[1837] 1827. The method of aspect 1593, wherein the method further comprises administering a tumor microenvironment-modulating agent.

[1838] 1828. The method of aspect 1827, wherein the tumor microenvironmentmodulating agent targets at least one of hypoxia, acidosis, or extracellular matrix stiffness.

[1839] 1829. The method of aspect 1593, wherein the method further comprises administering an agent that enhances antigen presentation.

[1840] 1830. The method of aspect 1829, wherein the agent that enhances antigen presentation is a GM-CSF fusion protein.

[1841] 1831. The method of aspect 1593, wherein the method further comprises administering a tumor-specific peptide.

[1842] 1832. The method of aspect 1831, wherein the tumor-specific peptide is derived from a tumor-associated antigen selected from the group consisting of NY-ESO-1, WT1, and MAGE- A3.

[1843] 1833. The method of aspect 1593, wherein the method further comprises administering a tumor-specific RNA vaccine.

[1844] 1834. The method of aspect 1833, wherein the RNA vaccine encodes a tumor-associated antigen.

[1845] 1835. The method of aspect 1593, wherein the method further comprises administering a tumor-specific DNA vaccine.

[1846] 1836. The method of aspect 1835, wherein the DNA vaccine encodes a tumor-associated antigen.

[1847] 1837. The method of aspect 1593, wherein the method further comprises administering a viral-based vaccine.

[1848] 1838. The method of aspect 1837, wherein the viral-based vaccine is an adenovirus-based vaccine.

[1849] 1839. The method of aspect 1593, wherein the method further comprises administering a peptide-MHC complex.

[1850] 1840. The method of aspect 1839, wherein the peptide-MHC complex targets a tumor-specific neoantigen.

[1851] 1841. The method of aspect 1593, wherein the method further comprises administering a tumor-specific antibody-drug conjugate.

[1852] 1842. The method of aspect 1841, wherein the antibody-drug conjugate targets a tumor-associated antigen.Immorta-ANKC-PCT

[1853] 1843. The method of aspect 1593, wherein the method further comprises administering a tumor-specific radioconjugate.

[1854] 1844. The method of aspect 1843, wherein the radioconjugate uses an isotope selected from the group consisting of iodine-131 and yttrium-90.

[1855] 1845. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immunotoxin.

[1856] 1846. The method of aspect 1845, wherein the immunotoxin targets a tumor-associated antigen.

[1857] 1847. The method of aspect 1593, wherein the method further comprises administering a tumor-specific small molecule-drug conjugate.

[1858] 1848. The method of aspect 1847, wherein the small molecule-drug conjugate targets a tumor-associated pathway.

[1859] 1849. The method of aspect 1593, wherein the method further comprises administering a tumor-specific nanobody.

[1860] 1850. The method of aspect 1849, wherein the nanobody targets a tumor-associated antigen.

[1861] 1851. The method of aspect 1593, wherein the method further comprises administering a tumor-specific aptamer.

[1862] 1852. The method of aspect 1851, wherein the aptamer targets a tumor-associated antigen.

[1863] 1853. The method of aspect 1593, wherein the method further comprises administering a tumor-specific peptide-drug conjugate.

[1864] 1854. The method of aspect 1853, wherein the peptide-drug conjugate targets a tumor-associated antigen.

[1865] 1855. The method of aspect 1593, wherein the method further comprises administering a tumor-specific oncolytic peptide.

[1866] 1856. The method of aspect 1855, wherein the oncolytic peptide induces tumor cell lysis.

[1867] 1857. The method of aspect 1593, wherein the method further comprises administering a tumor-specific small molecule inhibitor.

[1868] 1858. The method of aspect 1857, wherein the small molecule inhibitor targets a tumor-associated pathway selected from the group consisting of MAPK, JAK / STAT, and TGF-β.Immorta-ANKC-PCT

[1869] 1859. The method of aspect 1593, wherein the method further comprises administering a tumor-specific protein kinase inhibitor.

[1870] 1860. The method of aspect 1859, wherein the protein kinase inhibitor targets at least one kinase selected from the group consisting of ALK, BTK, and KIT.

[1871] 1861. The method of aspect 1593, wherein the method further comprises administering a tumor-specific phosphatase inhibitor.

[1872] 1862. The method of aspect 1861, wherein the phosphatase inhibitor targets PTEN.

[1873] 1863. The method of aspect 1593, wherein the method further comprises administering a tumor-specific G-protein-coupled receptor (GPCR) modulator.

[1874] 1864. The method of aspect 1863, wherein the GPCR modulator targets at least one receptor selected from the group consisting of CXCR4 and CCR7.

[1875] 1865. The method of aspect 1593, wherein the method further comprises administering a tumor-specific ion channel modulator.

[1876] 1866. The method of aspect 1865, wherein the ion channel modulator targets a calcium channel.

[1877] 1867. The method of aspect 1593, wherein the method further comprises administering a tumor-specific transporter inhibitor.

[1878] 1868. The method of aspect 1867, wherein the transporter inhibitor targets a glucose transporter.

[1879] 1869. The method of aspect 1593, wherein the method further comprises administering a tumor-specific nuclear receptor modulator.

[1880] 1870. The method of aspect 1869, wherein the nuclear receptor modulator targets at least one receptor selected from the group consisting of androgen receptor (AR) and estrogen receptor (ER).

[1881] 1871. The method of aspect 1593, wherein the method further comprises administering a tumor-specific transcription factor inhibitor.

[1882] 1872. The method of aspect 1871, wherein the transcription factor inhibitor targets at least one transcription factor selected from the group consisting of MYC, HIF-1α, and NF-κB.

[1883] 1873. The method of aspect 1593, wherein the method further comprises administering a tumor-specific epigenetic modulator.

[1884] 1874. The method of aspect 1873, wherein the epigenetic modulator targets at least one enzyme selected from the group consisting of EZH2 and DNMT1.Immorta-ANKC-PCT

[1885] 1875. The method of aspect 1593, wherein the method further comprises administering a tumor-specific proteasome activator.

[1886] 1876. The method of aspect 1875, wherein the proteasome activator enhances antigen presentation.

[1887] 1877. The method of aspect 1593, wherein the method further comprises administering a tumor-specific autophagy modulator.

[1888] 1878. The method of aspect 1877, wherein the autophagy modulator inhibits autophagy.

[1889] 1879. The method of aspect 1593, wherein the method further comprises administering a tumor-specific apoptosis inducer.

[1890] 1880. The method of aspect 1879, wherein the apoptosis inducer is a BH3 mimetic.

[1891] 1881. The method of aspect 1593, wherein the method further comprises administering a tumor-specific necroptosis inducer.

[1892] 1882. The method of aspect 1881, wherein the necroptosis inducer targets RIPK1.

[1893] 1883. The method of aspect 1593, wherein the method further comprises administering a tumor-specific ferroptosis inducer.

[1894] 1884. The method of aspect 1883, wherein the ferroptosis inducer targets GPX4.

[1895] 1885. The method of aspect 1593, wherein the method further comprises administering a tumor-specific pyroptosis inducer.

[1896] 1886. The method of aspect 1885, wherein the pyroptosis inducer targets caspase- 1.

[1897] 1887. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-recruiting agent.

[1898] 1888. The method of aspect 1887, wherein the immune cell -recruiting agent is a chemokine selected from the group consisting of CCL5, CXCL9, and CXCL10.

[1899] 1889. The method of aspect 1593, wherein the method further comprises administering a tumor-specific cytokine fusion protein.

[1900] 1890. The method of aspect 1889, wherein the cytokine fusion protein includes IL-15.

[1901] 1891. The method of aspect 1593, wherein the method further comprises administering a tumor-specific bispecific T cell engager (BiTE).Immorta-ANKC-PCT

[1902] 1892. The method of aspect 1891, wherein the BiTE targets CD3 and a tumor-associated antigen.

[1903] 1893. The method of aspect 1593, wherein the method further comprises administering a tumor-specific trispecific antibody.

[1904] 1894. The method of aspect 1893, wherein the trispecific antibody targets CD3, a tumor-associated antigen, and an NK cell receptor.

[1905] 1895. The method of aspect 1593, wherein the method further comprises administering a tumor-specific antibody-dependent cell-mediated cytotoxicity (ADCC) enhancer.

[1906] 1896. The method of aspect 1895, wherein the ADCC enhancer is an antiCD 16 antibody.

[1907] 1897. The method of aspect 1593, wherein the method further comprises administering a tumor-specific complement-dependent cytotoxicity (CDC) enhancer.

[1908] 1898. The method of aspect 1897, wherein the CDC enhancer is an antiCD 55 antibody.

[1909] 1899. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-editing agent.

[1910] 1900. The method of aspect 1899, wherein the immune cell-editing agent uses CRISPR to enhance NK cell function.

[1911] 1901. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-reprogramming agent.

[1912] 1902. The method of aspect 1901, wherein the immune cell -reprogramming agent converts M2 macrophages to Ml macrophages.

[1913] 1903. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-trafficking agent.

[1914] 1904. The method of aspect 1903, wherein the immune cell-trafficking agent enhances NK cell homing to metastatic sites.

[1915] 1905. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-survival agent.

[1916] 1906. The method of aspect 1905, wherein the immune cell-survival agent is an anti-apoptotic protein.

[1917] 1907. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-proliferation agent.Immorta-ANKC-PCT

[1918] 1908. The method of aspect 1907, wherein the immune cell-proliferation agent is a growth factor.

[1919] 1909. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-differentiation agent.

[1920] 1910. The method of aspect 1909, wherein the immune cell-differentiation agent promotes NK cell differentiation.

[1921] 1911. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-activation agent.

[1922] 1912. The method of aspect 1911, wherein the immune cell-activation agent is a CD137 agonist.

[1923] 1913. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-exhaustion inhibitor.

[1924] 1914. The method of aspect 1913, wherein the immune cell-exhaustion inhibitor targets LAG-3.

[1925] 1915. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-senescence inhibitor.

[1926] 1916. The method of aspect 1915, wherein the immune cell-senescence inhibitor targets p16.

[1927] 1917. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-metabolism modulator.

[1928] 1918. The method of aspect 1917, wherein the immune cell-metabolism modulator enhances NK cell glycolysis.

[1929] 1919. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-signaling modulator.

[1930] 1920. The method of aspect 1919, wherein the immune cell-signaling modulator enhances NK cell receptor signaling.

[1931] 1921. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-adhesion modulator.

[1932] 1922. The method of aspect 1921, wherein the immune cell-adhesion modulator enhances NK cell adhesion to tumor cells.

[1933] 1923. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-migration modulator.

[1934] 1924. The method of aspect 1923, wherein the immune cell-migration modulator enhances NK cell migration to metastatic sites.Immorta-ANKC-PCT

[1935] 1925. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-cytotoxicity enhancer.

[1936] 1926. The method of aspect 1925, wherein the immune cell-cytotoxicity enhancer increases perforin expression in NK cells.

[1937] 1927. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-memory inducer.

[1938] 1928. The method of aspect 1927, wherein the immune cell-memory inducer promotes memory NK cell formation.

[1939] 1929. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-stemness modulator.

[1940] 1930. The method of aspect 1929, wherein the immune cell -sternness modulator enhances NK cell sternness.

[1941] 1931. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-plasticity modulator.

[1942] 1932. The method of aspect 1931, wherein the immune cell-plasticity modulator enhances NK cell plasticity.

[1943] 1933. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-epigenetic modulator.

[1944] 1934. The method of aspect 1933, wherein the immune cell-epigenetic modulator enhances NK cell effector function.

[1945] 1935. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-transcriptional regulator.

[1946] 1936. The method of aspect 1935, wherein the immune cell-transcriptional regulator enhances NK cell gene expression.

[1947] 1937. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-post-translational modifier.

[1948] 1938. The method of aspect 1937, wherein the immune cell-post-translational modifier enhances NK cell activation.

[1949] 1939. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-protein degradation modulator.

[1950] 1940. The method of aspect 1939, wherein the immune cell-protein degradation modulator enhances NK cell protein turnover.

[1951] 1941. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-protein synthesis modulator.Immorta-ANKC-PCT

[1952] 1942. The method of aspect 1941, wherein the immune cell-protein synthesis modulator enhances NK cell cytokine production.

[1953] 1943. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-DNA repair modulator.

[1954] 1944. The method of aspect 1943, wherein the immune cell-DNA repair modulator enhances NK cell survival.

[1955] 1945. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-RNA repair modulator.

[1956] 1946. The method of aspect 1945, wherein the immune cell-RNA repair modulator enhances NK cell function.

[1957] 1947. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-lipid metabolism modulator.

[1958] 1948. The method of aspect 1947, wherein the immune cell-lipid metabolism modulator enhances NK cell membrane fluidity.

[1959] 1949. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-glucose metabolism modulator.

[1960] 1950. The method of aspect 1949, wherein the immune cell-glucose metabolism modulator enhances NK cell energy production.

[1961] 1951. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-amino acid metabolism modulator.

[1962] 1952. The method of aspect 1951, wherein the immune cell-amino acid metabolism modulator enhances NK cell proliferation.

[1963] 1953. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-nucleotide metabolism modulator.

[1964] 1954. The method of aspect 1953, wherein the immune cell-nucleotide metabolism modulator enhances NK cell DNA synthesis.

[1965] 1955. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-mitochondrial function modulator.

[1966] 1956. The method of aspect 1955, wherein the immune cell-mitochondrial function modulator enhances NK cell ATP production.

[1967] 1957. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-lysosomal function modulator.

[1968] 1958. The method of aspect 1957, wherein the immune cell-lysosomal function modulator enhances NK cell antigen processing.Immorta-ANKC-PCT

[1969] 1959. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-endoplasmic reticulum (ER) stress modulator.

[1970] 1960. The method of aspect 1959, wherein the immune cell-ER stress modulator enhances NK cell protein folding.

[1971] 1961. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-Golgi apparatus function modulator.

[1972] 1962. The method of aspect 1961, wherein the immune cell-Golgi apparatus function modulator enhances NK cell protein trafficking.

[1973] 1963. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-cytoskeletal modulator.

[1974] 1964. The method of aspect 1963, wherein the immune cell-cytoskeletal modulator enhances NK cell migration.

[1975] 1965. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-nuclear transport modulator.

[1976] 1966. The method of aspect 1965, wherein the immune cell-nuclear transport modulator enhances NK cell transcription factor activity.

[1977] 1967. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-chromatin remodeling modulator.

[1978] 1968. The method of aspect 1967, wherein the immune cell-chromatin remodeling modulator enhances NK cell gene expression.

[1979] 1969. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-histone modification modulator.

[1980] 1970. The method of aspect 1969, wherein the immune cell-histone modification modulator enhances NK cell effector function.

[1981] 1971. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-DNA methylation modulator.

[1982] 1972. The method of aspect 1971, wherein the immune cell-DNA methylation modulator enhances NK cell activation.

[1983] 1973. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-RNA methylation modulator.

[1984] 1974. The method of aspect 1973, wherein the immune cell-RNA methylation modulator enhances NK cell mRNA stability.Immorta-ANKC-PCT

[1985] 1975. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-protein methylation modulator.

[1986] 1976. The method of aspect 1975, wherein the immune cell-protein methylation modulator enhances NK cell signaling.

[1987] 1977. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-protein acetylation modulator.

[1988] 1978. The method of aspect 1977, wherein the immune cell-protein acetylation modulator enhances NK cell transcription.

[1989] 1979. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-protein phosphorylation modulator.

[1990] 1980. The method of aspect 1979, wherein the immune cell-protein phosphorylation modulator enhances NK cell signaling.

[1991] 1981. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-protein ubiquitination modulator.

[1992] 1982. The method of aspect 1981, wherein the immune cell-protein ubiquitination modulator enhances NK cell protein turnover.

[1993] 1983. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-protein sumoylation modulator.

[1994] 1984. The method of aspect 1983, wherein the immune cell-protein sumoylation modulator enhances NK cell function.

[1995] 1985. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-protein neddylation modulator.

[1996] 1986. The method of aspect 1985, wherein the immune cell-protein neddylation modulator enhances NK cell survival.

[1997] 1987. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-protein glycosylation modulator.

[1998] 1988. The method of aspect 1987, wherein the immune cell-protein glycosylation modulator enhances NK cell receptor stability.

[1999] 1989. The method of aspect 1593, wherein the method further comprises administering a tumor-specific immune cell-protein lipidation modulator.

[2000] 1990. A method of increasing dendritic cell maturation in a cancer patient, said method comprising administration of one or more NK cell activators, and / or administering exogenous dendritic cells, and / or administering one or more senolytics, wherein said dendritic cell maturation leads to enhanced immune responses to tumors,Immorta-ANKC-PCTwherein said immune responses are either naturally occurring immune responses and / or immune responses triggered by one or more external stimuli.

[2001] 1991. The method of aspect 1990, wherein the one or more NK cell activators are administered.

[2002] 1992. The method of aspect 1991, wherein the one or more NK cell activators are naturally occurring compounds.

[2003] 1993. The method of aspect 1992, wherein the naturally occurring compounds are selected from the group consisting of beta-glucans, arabinogalactans, fucoidans, curcumin, resveratrol, and epigallocatechin gallate (EGCG).

[2004] 1994. The method of aspect 1993, wherein the naturally occurring compound is a beta-glucan derived from a source selected from the group consisting of mushrooms, yeast, and oats.

[2005] 1995. The method of aspect 1994, wherein the beta-glucan is derived from a mushroom selected from the group consisting of reishi, shiitake, and maitake.

[2006] 1996. The method of aspect 1993, wherein the naturally occurring compound is curcumin.

[2007] 1997. The method of aspect 1993, wherein the naturally occurring compound is resveratrol.

[2008] 1998. The method of aspect 1993, wherein the naturally occurring compound is epigallocatechin gallate (EGCG).

[2009] 1999. The method of aspect 1991, wherein the one or more NK cell activators include a cytokine.

[2010] 2000. The method of aspect 1999, wherein the cytokine is selected from the group consisting of IL-2, IL- 15, IL- 18, and IL-21.

[2011] 2001. The method of aspect 2000, wherein the cytokine is IL-2.

[2012] 2002. The method of aspect 2000, wherein the cytokine is IL-15.

[2013] 2003. The method of aspect 2000, wherein the cytokine is IL-18.

[2014] 2004. The method of aspect 2000, wherein the cytokine is IL-21.

[2015] 2005. The method of aspect 1991, wherein the one or more NK cell activators include a monoclonal antibody.

[2016] 2006. The method of aspect 2005, wherein the monoclonal antibody targets at least one NK cell-activating receptor selected from the group consisting of NKG2D, NKp46, and NKp30.Immorta-ANKC-PCT

[2017] 2007. The method of aspect 1991, wherein the one or more NK cell activators increase NK cell cytotoxicity against tumor cells by at least 10% compared to NK cells not exposed to the activators.

[2018] 2008. The method of aspect 1991, wherein the one or more NK cell activators are administered at a dose ranging from 0.5 mg / kg to 200 mg / kg of the patient’s body weight.

[2019] 2009. The method of aspect 1990, wherein the exogenous dendritic cells are administered.

[2020] 2010. The method of aspect 2009, wherein the exogenous dendritic cells are autologous.

[2021] 2011. The method of aspect 2009, wherein the exogenous dendritic cells are allogeneic.

[2022] 2012. The method of aspect 2011, wherein the allogeneic dendritic cells are derived from a healthy donor.

[2023] 2013. The method of aspect 2009, wherein the exogenous dendritic cells are derived from an induced pluripotent stem cell (iPSC) source.

[2024] 2014. The method of aspect 2009, wherein the exogenous dendritic cells are pulsed with one or more tumor-associated antigens ex vivo prior to administration.

[2025] 2015. The method of aspect 2014, wherein the one or more tumor-associated antigens are selected from the group consisting of HER2, MUC1, PSA, and CEA.

[2026] 2016. The method of aspect 2015, wherein the tumor-associated antigen is HER2.

[2027] 2017. The method of aspect 2015, wherein the tumor-associated antigen is MUC1.

[2028] 2018. The method of aspect 2015, wherein the tumor-associated antigen is PSA.

[2029] 2019. The method of aspect 2015, wherein the tumor-associated antigen is CEA.

[2030] 2020. The method of aspect 2009, wherein the exogenous dendritic cells are genetically modified.

[2031] 2021. The method of aspect 2020, wherein the exogenous dendritic cells are modified to overexpress at least one co-stimulatory molecule selected from the group consisting of CD80, CD86, and CD40.Immorta-ANKC-PCT

[2032] 2022. The method of aspect 2009, wherein the exogenous dendritic cells are matured ex vivo prior to administration.

[2033] 2023. The method of aspect 2022, wherein the ex vivo maturation includes culturing the dendritic cells in the presence of at least one maturation factor selected from the group consisting of TNF-α, IL-1β, IL-6, and prostaglandin E2 (PGE2).

[2034] 2024. The method of aspect 2009, wherein the exogenous dendritic cells are administered at a dose ranging from 1 x 106to 1 x 109cells per administration.

[2035] 2025. The method of aspect 1990, wherein the one or more senolytics are administered.

[2036] 2026. The method of aspect 2025, wherein the one or more senolytics selectively induce apoptosis in senescent tumor cells.

[2037] 2027. The method of aspect 2025, wherein the one or more senolytics are selected from the group consisting of dasatinib, quercetin, navitoclax, and fisetin.

[2038] 2028. The method of aspect 2027, wherein the one or more senolytics include dasatinib.

[2039] 2029. The method of aspect 2027, wherein the one or more senolytics include quercetin.

[2040] 2030. The method of aspect 2027, wherein the one or more senolytics include navitoclax.

[2041] 2031. The method of aspect 2027, wherein the one or more senolytics include fisetin.

[2042] 2032. The method of aspect 2025, wherein the one or more senolytics are administered at a dose ranging from 0.1 mg / kg to 100 mg / kg of the patient’s body weight.

[2043] 2033. The method of aspect 1990, wherein the dendritic cell maturation is increased by at least 10% compared to dendritic cells in a cancer patient not receiving the method.

[2044] 2034. The method of aspect 1990, wherein the dendritic cell maturation is determined by an increase in the expression of at least one maturation marker selected from the group consisting of CD83, CD86, and MHC class II.

[2045] 2035. The method of aspect 1990, wherein the enhanced immune responses to tumors include an increase in T cell responses.

[2046] 2036. The method of aspect 2035, wherein the T cell responses include CD8+ T cell responses.Immorta-ANKC-PCT

[2047] 2037. The method of aspect 2035, wherein the T cell responses include CD4+ T cell responses.

[2048] 2038. The method of aspect 1990, wherein the enhanced immune responses to tumors include an increase in NK cell activity.

[2049] 2039. The method of aspect 1990, wherein the enhanced immune responses to tumors include an increase in the production of at least one cytokine selected from the group consisting of IFN-γ, TNF-a, and IL-12.

[2050] 2040. The method of aspect 1990, wherein the enhanced immune responses to tumors result in a reduction in tumor burden by at least 10%.

[2051] 2041. The method of aspect 1990, wherein the immune responses are naturally occurring immune responses.

[2052] 2042. The method of aspect 1990, wherein the immune responses are triggered by one or more external stimuli.

[2053] 2043. The method of aspect 2042, wherein the one or more external stimuli include a tumor vaccine.

[2054] 2044. The method of aspect 2043, wherein the tumor vaccine comprises one or more tumor-associated antigens selected from the group consisting of HER2, MUC1, PSA, and CEA.

[2055] 2045. The method of aspect 2043, wherein the tumor vaccine is a peptide-based vaccine.

[2056] 2046. The method of aspect 2043, wherein the tumor vaccine is an RNA-based vaccine.

[2057] 2047. The method of aspect 2043, wherein the tumor vaccine is a DNA-based vaccine.

[2058] 2048. The method of aspect 2043, wherein the tumor vaccine is a viral vector-based vaccine.

[2059] 2049. The method of aspect 2048, wherein the viral vector is an adenovirus.

[2060] 2050. The method of aspect 2042, wherein the one or more external stimuli include a tumor-specific neoantigen.

[2061] 2051. The method of aspect 2050, wherein the tumor-specific neoantigen is identified by sequencing the tumor genome of the patient.

[2062] 2052. The method of aspect 2042, wherein the one or more external stimuli include a tumor-specific peptide-MHC complex.Immorta-ANKC-PCT

[2063] 2053. The method of aspect 2042, wherein the one or more external stimuli include an immune checkpoint inhibitor.

[2064] 2054. The method of aspect 2053, wherein the immune checkpoint inhibitor targets at least one of PD-1, PD-L1, or CTLA-4.

[2065] 2055. The method of aspect 2054, wherein the immune checkpoint inhibitor is selected from the group consisting of pembrolizumab, nivolumab, and ipilimumab.

[2066] 2056. The method of aspect 2042, wherein the one or more external stimuli include a chemotherapeutic agent that induces immunogenic cell death.

[2067] 2057. The method of aspect 2056, wherein the chemotherapeutic agent is selected from the group consisting of anthracyclines, oxaliplatin, and cyclophosphamide.

[2068] 2058. The method of aspect 1990, wherein the cancer is a solid tumor.

[2069] 2059. The method of aspect 2058, wherein the solid tumor is selected from the group consisting of breast cancer, lung cancer, pancreatic cancer, colorectal cancer, and melanoma.

[2070] 2060. The method of aspect 2059, wherein the solid tumor is breast cancer.

[2071] 2061. The method of aspect 2059, wherein the solid tumor is lung cancer.

[2072] 2062. The method of aspect 2059, wherein the solid tumor is pancreatic cancer.

[2073] 2063. The method of aspect 2059, wherein the solid tumor is colorectal cancer.

[2074] 2064. The method of aspect 2059, wherein the solid tumor is melanoma.

[2075] 2065. The method of aspect 1990, wherein the cancer is a hematologic malignancy.

[2076] 2066. The method of aspect 2065, wherein the hematologic malignancy is selected from the group consisting of leukemia, lymphoma, and multiple myeloma.

[2077] 2067. The method of aspect 2066, wherein the hematologic malignancy is leukemia.

[2078] 2068. The method of aspect 2066, wherein the hematologic malignancy is lymphoma.

[2079] 2069. The method of aspect 2066, wherein the hematologic malignancy is multiple myeloma.

[2080] 2070. The method of aspect 1990, wherein the one or more NK cell activators, the exogenous dendritic cells, and / or the one or more senolytics are administered simultaneously.Immorta-ANKC-PCT

[2081] 2071. The method of aspect 1990, wherein the one or more NK cell activators, the exogenous dendritic cells, and / or the one or more senolytics are administered sequentially.

[2082] 2072. The method of aspect 2071, wherein the one or more senolytics are administered prior to the one or more NK cell activators and / or the exogenous dendritic cells.

[2083] 2073. The method of aspect 2071, wherein the one or more NK cell activators are administered prior to the exogenous dendritic cells and / or the one or more senolytics.

[2084] 2074. The method of aspect 1990, wherein the one or more NK cell activators are administered intravenously.

[2085] 2075. The method of aspect 1990, wherein the exogenous dendritic cells are administered intradermally.

[2086] 2076. The method of aspect 1990, wherein the one or more senolytics are administered orally.

[2087] 2077. The method of aspect 1990, wherein the administration occurs daily for a period of at least one week.

[2088] 2078. The method of aspect 1990, wherein the administration occurs weekly for a period of at least one month.

[2089] 2079. The method of aspect 1990, wherein the cancer patient is a human.

[2090] 2080. The method of aspect 1990, further comprising administering an additional therapeutic agent.

[2091] 2081. The method of aspect 2080, wherein the additional therapeutic agent is a chemotherapeutic agent.

[2092] 2082. The method of aspect 2081, wherein the chemotherapeutic agent is selected from the group consisting of paclitaxel, doxorubicin, and cisplatin.

[2093] 2083. The method of aspect 1990, further comprising monitoring the cancer patient for an increase in dendritic cell maturation.

[2094] 2084. The method of aspect 1990, further comprising monitoring the cancer patient for an increase in immune responses to tumors.

[2095] 2085. The method of aspect 1990, wherein the method increases the patient’s progression-free survival by at least 10% compared to a control group not receiving the combination.Immorta-ANKC-PCT

[2096] 2086. The method of aspect 1990, wherein the method increases the patient’s overall survival by at least 10% compared to a control group not receiving the combination.

[2097] 2087. The method of aspect 1990, wherein the cancer is metastatic.

[2098] 2088. The method of aspect 1990, wherein the cancer is refractory to at least one prior therapy.

[2099] 2089. The method of aspect 1990, wherein the one or more senolytics target at least one pathway selected from the group consisting of Bcl-2, PI3K / AKT, and p53.

[2100] 2090. The method of aspect 1990, wherein the method reduces the number of senescent cells in the tumor microenvironment by at least 20%.

[2101] 2091. The method of aspect 1990, wherein the method increases dendritic cell infiltration into the tumor by at least 15%.

[2102] 2092. The method of aspect 1990, wherein the one or more NK cell activators are administered in a liposomal formulation.

[2103] 2093. The method of aspect 1990, wherein the exogenous dendritic cells are cryopreserved prior to administration.

[2104] 2094. The method of aspect 1990, wherein the one or more senolytics are administered in a nanoparticle formulation.

[2105] 2095. The method of aspect 1990, wherein the method further comprises a step of identifying the cancer patient as having a tumor with high senescent cell burden prior to administration.

[2106] 2096. The method of aspect 2095, wherein the senescent cell burden is determined by measuring the expression of at least one senescence marker selected from the group consisting of p16, p21, and SA-β-gal.

[2107] 2097. The method of aspect 1990, wherein the method further comprises a step of identifying the cancer patient as having low dendritic cell maturation prior to administration.

[2108] 2098. The method of aspect 2097, wherein the dendritic cell maturation is determined by measuring the expression of at least one maturation marker selected from the group consisting of CD83, CD86, and MHC class II.

[2109] 2099. The method of aspect 1990, wherein the method further comprises a step of identifying the cancer patient as having low immune responses to tumors prior to administration.Immorta-ANKC-PCT

[2110] 2100. The method of aspect 2099, wherein the immune responses are measured by assessing the expression of at least one immune activation marker selected from the group consisting of CD69, IFN-γ, and IL-12.

[2111] 2101. The method of aspect 1990, wherein the one or more NK cell activators have a purity of at least 90%.

[2112] 2102. The method of aspect 1990, wherein the one or more senolytics have a purity of at least 90%.

[2113] 2103. The method of aspect 1990, wherein the method further comprises administering a dietary supplement to the cancer patient.

[2114] 2104. The method of aspect 2103, wherein the dietary supplement comprises at least one vitamin selected from the group consisting of vitamin C and vitamin D.

[2115] 2105. The method of aspect 1990, wherein the method further comprises subjecting the cancer patient to radiation therapy.

[2116] 2106. The method of aspect 1990, wherein the method further comprises surgically resecting a tumor from the cancer patient prior to administration.

[2117] 2107. The method of aspect 1990, wherein the method is used as an adjuvant therapy following a primary cancer treatment.

[2118] 2108. The method of aspect 1990, wherein the method is used as a neoadjuvant therapy prior to a primary cancer treatment.

[2119] 2109. The method of aspect 1990, wherein the method reduces cancer recurrence rates by at least 10% compared to a control group not receiving the combination.

[2120] 2110. The method of aspect 1990, wherein the method is performed in combination with a ketogenic diet.

[2121] 2111. The method of aspect 1990, wherein the method further comprises administering an agent capable of reducing T regulatory cell number and / or activity.

[2122] 2112. The method of aspect 2111, wherein the agent capable of reducing T regulatory cell number and / or activity is selected from the group consisting of cyclophosphamide, ipilimumab, and pembrolizumab.

[2123] 2113. The method of aspect 1990, wherein the method further comprises administering an agent that suppresses myeloid-derived suppressor cell (MDSC) number and / or function.Immorta-ANKC-PCT

[2124] 2114. The method of aspect 2113, wherein the agent that suppresses MDSC number and / or function is selected from the group consisting of all-trans retinoic acid (ATRA), sildenafil, and gemcitabine.

[2125] 2115. The method of aspect 1990, wherein the method further comprises administering a microbiome metabolite.

[2126] 2116. The method of aspect 2115, wherein the microbiome metabolite is a short-chain fatty acid selected from the group consisting of butyrate, propionate, and acetate.

[2127] 2117. The method of aspect 1990, wherein the method further comprises administering an agent that activates memory NK cells.

[2128] 2118. The method of aspect 2117, wherein the agent that activates memory NK cells is a cytokine selected from the group consisting of IL- 12, IL- 15, and IL- 18.

[2129] 2119. The method of aspect 1990, wherein the method further comprises administering exogenous NK cells.

[2130] 2120. The method of aspect 2119, wherein the exogenous NK cells are autologous.

[2131] 2121. The method of aspect 2119, wherein the exogenous NK cells are allogeneic.

[2132] 2122. The method of aspect 2119, wherein the exogenous NK cells are administered at a dose ranging from 1 x 106to 1 x 109cells per kg of the patient’s body weight.

[2133] 2123. The method of aspect 1990, wherein the method further comprises administering an anti-inflammatory agent.

[2134] 2124. The method of aspect 2123, wherein the anti-inflammatory agent is selected from the group consisting of aspirin, ibuprofen, and celecoxib.

[2135] 2125. The method of aspect 1990, wherein the method further comprises administering an antioxidant.

[2136] 2126. The method of aspect 2125, wherein the antioxidant is selected from the group consisting of N-acetylcysteine, glutathione, and coenzyme Q10.

[2137] 2127. The method of aspect 1990, wherein the method further comprises administering a CAR-T cell therapy.

[2138] 2128. The method of aspect 1990, wherein the method further comprises administering an oncolytic virus.Immorta-ANKC-PCT

[2139] 2129. The method of aspect 2128, wherein the oncolytic virus is selected from the group consisting of talimogene laherparepvec, reovirus, and vaccinia virus.

[2140] 2130. The method of aspect 1990, wherein the method further comprises administering a histone deacetylase (HDAC) inhibitor.

[2141] 2131. The method of aspect 2130, wherein the HDAC inhibitor is selected from the group consisting of vorinostat, romidepsin, and panobinostat.

[2142] 2132. The method of aspect 1990, wherein the method further comprises administering a DNA methyltransferase inhibitor.

[2143] 2133. The method of aspect 2132, wherein the DNA methyltransferase inhibitor is selected from the group consisting of azacitidine and decitabine.

[2144] 2134. The method of aspect 1990, wherein the method further comprises administering a tyrosine kinase inhibitor.

[2145] 2135. The method of aspect 2134, wherein the tyrosine kinase inhibitor is selected from the group consisting of erlotinib, gefitinib, and osimertinib.

[2146] 2136. The method of aspect 1990, wherein the method further comprises administering a proteasome inhibitor.

[2147] 2137. The method of aspect 2136, wherein the proteasome inhibitor is selected from the group consisting of bortezomib, carfilzomib, and ixazomib.

[2148] 2138. The method of aspect 1990, wherein the method further comprises administering a PARP inhibitor.

[2149] 2139. The method of aspect 2138, wherein the PARP inhibitor is selected from the group consisting of olaparib, rucaparib, and niraparib.

[2150] 2140. The method of aspect 1990, wherein the method further comprises administering a BCL-2 inhibitor.

[2151] 2141. The method of aspect 2140, wherein the BCL-2 inhibitor is venetoclax.

[2152] 2142. The method of aspect 1990, wherein the method further comprises administering an mTOR inhibitor.

[2153] 2143. The method of aspect 2142, wherein the mTOR inhibitor is selected from the group consisting of rapamycin, everolimus, and temsirolimus.

[2154] 2144. The method of aspect 1990, wherein the method further comprises administering a PI3K inhibitor.

[2155] 2145. The method of aspect 2144, wherein the PI3K inhibitor is selected from the group consisting of idelalisib, copanlisib, and duvelisib.Immorta-ANKC-PCT

[2156] 2146. The method of aspect 1990, wherein the method further comprises administering a CDK4 / 6 inhibitor.

[2157] 2147. The method of aspect 2146, wherein the CDK4 / 6 inhibitor is selected from the group consisting of palbociclib, ribociclib, and abemaciclib.

[2158] 2148. The method of aspect 1990, wherein the method further comprises administering an anti -angiogenic agent.

[2159] 2149. The method of aspect 2148, wherein the anti -angiogenic agent is selected from the group consisting of bevacizumab, sorafenib, and lenvatinib.

[2160] 2150. The method of aspect 1990, wherein the method further comprises administering a bispecific antibody.

[2161] 2151. The method of aspect 2150, wherein the bispecific antibody targets at least one of CD3 and a tumor-associated antigen.

[2162] 2152. The method of aspect 1990, wherein the method further comprises administering an adoptive cell therapy.

[2163] 2153. The method of aspect 2152, wherein the adoptive cell therapy comprises T cells.

[2164] 2154. The method of aspect 1990, wherein the method further comprises administering a tumor necrosis factor (TNF) superfamily agonist.

[2165] 2155. The method of aspect 2154, wherein the TNF superfamily agonist is a GITR agonist.

[2166] 2156. The method of aspect 1990, wherein the method further comprises administering a toll-like receptor (TLR) agonist.

[2167] 2157. The method of aspect 2156, wherein the TLR agonist is selected from the group consisting of imiquimod, resiquimod, and CpG oligodeoxynucleotides.

[2168] 2158. The method of aspect 1990, wherein the method further comprises administering a STING agonist.

[2169] 2159. The method of aspect 2158, wherein the STING agonist is a cyclic dinucleotide.

[2170] 2160. The method of aspect 1990, wherein the method further comprises administering a radiotherapy sensitizer.

[2171] 2161. The method of aspect 2160, wherein the radiotherapy sensitizer is a PARP inhibitor.

[2172] 2162. The method of aspect 1990, wherein the method further comprises administering a hypoxia-targeting agent.Immorta-ANKC-PCT

[2173] 2163. The method of aspect 2162, wherein the hypoxia-targeting agent is tirapazamine.

[2174] 2164. The method of aspect 1990, wherein the method further comprises administering a cancer stem cell-targeting agent.

[2175] 2165. The method of aspect 2164, wherein the cancer stem cell-targeting agent targets at least one pathway selected from the group consisting of Wnt, Notch, and Hedgehog.

[2176] 2166. The method of aspect 1990, wherein the method further comprises administering a metabolic inhibitor.

[2177] 2167. The method of aspect 2166, wherein the metabolic inhibitor targets at least one of glycolysis, glutaminolysis, or fatty acid synthesis.

[2178] 2168. The method of aspect 1990, wherein the method further comprises administering an immune adjuvant.

[2179] 2169. The method of aspect 2168, wherein the immune adjuvant is selected from the group consisting of alum, MF59, and AS03.

[2180] 2170. The method of aspect 1990, wherein the method further comprises administering a peptide-based therapeutic.

[2181] 2171. The method of aspect 2170, wherein the peptide-based therapeutic targets a tumor-associated antigen.

[2182] 2172. The method of aspect 1990, wherein the method further comprises administering a small interfering RNA (siRNA).

[2183] 2173. The method of aspect 2172, wherein the siRNA targets a gene associated with tumor cell survival.

[2184] 2174. The method of aspect 2173, wherein the gene is selected from the group consisting of MYC, KRAS, and EGFR.

[2185] 2175. The method of aspect 1990, wherein the method further comprises administering a CRISPR-based therapeutic.

[2186] 2176. The method of aspect 2175, wherein the CRISPR-based therapeutic targets a gene associated with tumor cell survival.

[2187] 2177. The method of aspect 2176, wherein the gene is selected from the group consisting of MYC, KRAS, and EGFR.

[2188] 2178. The method of aspect 1990, wherein the method further comprises administering a nanoparticle-based therapeutic.Immorta-ANKC-PCT

[2189] 2179. The method of aspect 2178, wherein the nanoparticle-based therapeutic delivers the one or more NK cell activators.

[2190] 2180. The method of aspect 1990, wherein the method further comprises administering a photodynamic therapy agent.

[2191] 2181. The method of aspect 2180, wherein the photodynamic therapy agent is a porphyrin derivative.

[2192] 2182. The method of aspect 1990, wherein the method further comprises administering a radiofrequency ablation therapy.

[2193] 2183. The method of aspect 1990, wherein the method further comprises administering a cryoablation therapy.

[2194] 2184. The method of aspect 1990, wherein the method further comprises administering a high-intensity focused ultrasound (HIFU) therapy.

[2195] 2185. The method of aspect 1990, wherein the method further comprises administering a laser interstitial thermal therapy (LITT).

[2196] 2186. The method of aspect 1990, wherein the method further comprises administering a targeted alpha therapy.

[2197] 2187. The method of aspect 2186, wherein the targeted alpha therapy uses an isotope selected from the group consisting of actinium-225 and bismuth-213.

[2198] 2188. The method of aspect 1990, wherein the method further comprises administering a boron neutron capture therapy (BNCT).

[2199] 2189. The method of aspect 1990, wherein the method further comprises administering a proton therapy.

[2200] 2190. The method of aspect 1990, wherein the method further comprises administering a carbon ion therapy.

[2201] 2191. The method of aspect 1990, wherein the method further comprises administering a stereotactic radiosurgery.

[2202] 2192. The method of aspect 1990, wherein the method further comprises administering a brachytherapy.

[2203] 2193. The method of aspect 1990, wherein the method further comprises administering a gene therapy.

[2204] 2194. The method of aspect 2193, wherein the gene therapy introduces a gene encoding a cytokine that enhances anti-tumor immunity.

[2205] 2195. The method of aspect 2194, wherein the cytokine is selected from the group consisting of IL-12, GM-CSF, and IFN-γ.Immorta-ANKC-PCT

[2206] 2196. The method of aspect 1990, wherein the method further comprises administering a viral vector-based therapy.

[2207] 2197. The method of aspect 2196, wherein the viral vector is an adeno-associated virus (AAV).

[2208] 2198. The method of aspect 1990, wherein the method further comprises administering a lipid nanoparticle-based therapy.

[2209] 2199. The method of aspect 2198, wherein the lipid nanoparticle delivers an mRNA encoding an immune-stimulatory protein.

[2210] 2200. The method of aspect 1990, wherein the method further comprises administering a natural product-based therapeutic.

[2211] 2201. The method of aspect 2200, wherein the natural product-based therapeutic is derived from a plant source.

[2212] 2202. The method of aspect 2201, wherein the plant source is selected from the group consisting of turmeric, green tea, and ginseng.

[2213] 2203. The method of aspect 1990, wherein the method further comprises administering a microbiome-modulating agent.

[2214] 2204. The method of aspect 2203, wherein the microbiome-modulating agent is a probiotic comprising at least one strain selected from the group consisting of Lactobacillus acidophilus and Bifidobacterium longum.

[2215] 2205. The method of aspect 2203, wherein the microbiome-modulating agent is a prebiotic selected from the group consisting of inulin, fructooligosaccharides (FOS), and galactooligosaccharides (GOS).

[2216] 2206. The method of aspect 1990, wherein the method further comprises administering a chemotherapeutic agent that enhances T cell priming.

[2217] 2207. The method of aspect 2206, wherein the chemotherapeutic agent is cyclophosphamide.

[2218] 2208. The method of aspect 1990, wherein the method further comprises administering a tumor microenvironment-modulating agent.

[2219] 2209. The method of aspect 2208, wherein the tumor microenvironmentmodulating agent targets at least one of hypoxia, acidosis, or extracellular matrix stiffness.

[2220] 2210. The method of aspect 1990, wherein the method further comprises administering an agent that enhances antigen presentation.Immorta-ANKC-PCT

[2221] 2211. The method of aspect 2210, wherein the agent that enhances antigen presentation is a GM-CSF fusion protein.

[2222] 2212. The method of aspect 1990, wherein the method further comprises administering a tumor-specific peptide.

[2223] 2213. The method of aspect 2212, wherein the tumor-specific peptide is derived from a tumor-associated antigen selected from the group consisting of NY-ESO-1, WT1, and MAGE- A3.

[2224] 2214. The method of aspect 1990, wherein the method further comprises administering a tumor-specific RNA vaccine.

[2225] 2215. The method of aspect 2214, wherein the RNA vaccine encodes a tumor-associated antigen.

[2226] 2216. The method of aspect 1990, wherein the method further comprises administering a tumor-specific DNA vaccine.

[2227] 2217. The method of aspect 2216, wherein the DNA vaccine encodes a tumor-associated antigen.

[2228] 2218. The method of aspect 1990, wherein the method further comprises administering a viral-based vaccine.

[2229] 2219. The method of aspect 2218, wherein the viral -based vaccine is an adenovirus-based vaccine.

[2230] 2220. The method of aspect 1990, wherein the method further comprises administering a tumor-specific antibody-drug conjugate.

[2231] 2221. The method of aspect 2220, wherein the antibody-drug conjugate targets a tumor-associated antigen.

[2232] . The method of aspect 1990, wherein the method further comprises administering a tumor-specific radioconjugate.

[2233] 2223. The method of aspect 1 1, wherein the radioconjugate uses an isotope selected from the group consisting of iodine-131 and yttrium-90.

[2234] 2224. The method of aspect 1990, wherein the method further comprises administering a tumor-specific immunotoxin.

[2235] 2225. The method of aspect 2224, wherein the immunotoxin targets a tumor-associated antigen.

[2236] 2226. The method of aspect 1990, wherein the method further comprises administering a tumor-specific small molecule-drug conjugate.Immorta-ANKC-PCT

[2237] 2227. The method of aspect 2226, wherein the small molecule-drug conjugate targets a tumor-associated pathway.

[2238] 2228. The method of aspect 1990, wherein the method further comprises administering a tumor-specific nanobody.

[2239] 2229. The method of aspect 2228, wherein the nanobody targets a tumor-associated antigen.

[2240] 2230. The method of aspect 1990, wherein the method further comprises administering a tumor-specific aptamer.

[2241] 2231. The method of aspect 2230, wherein the aptamer targets a tumor-associated antigen.

[2242] 2232. The method of aspect 1990, wherein the method further comprises administering a tumor-specific peptide-drug conjugate.

[2243] 2233. The method of aspect 2232, wherein the peptide-drug conjugate targets a tumor-associated antigen.

[2244] 2234. The method of aspect 1990, wherein the method further comprises administering a tumor-specific oncolytic peptide.

[2245] 2235. The method of aspect 2234, wherein the oncolytic peptide induces tumor cell lysis.

[2246] 2236. The method of aspect 1990, wherein the method further comprises administering a tumor-specific small molecule inhibitor.

[2247] 2237. The method of aspect 2236, wherein the small molecule inhibitor targets a tumor-associated pathway selected from the group consisting of MAPK, JAK / STAT, and TGF-β.

[2248] 2238. The method of aspect 1990, wherein the method further comprises administering a tumor-specific protein kinase inhibitor.

[2249] 2239. The method of aspect 2238, wherein the protein kinase inhibitor targets at least one kinase selected from the group consisting of ALK, BTK, and KIT.

[2250] 2240. The method of aspect 1990, wherein the method further comprises administering a tumor-specific phosphatase inhibitor.

[2251] 2241. The method of aspect 2240, wherein the phosphatase inhibitor targets PTEN.

[2252] 2242. The method of aspect 1990, wherein the method further comprises administering a tumor-specific G-protein-coupled receptor (GPCR) modulator.Immorta-ANKC-PCT

[2253] 2243. The method of aspect 2242, wherein the GPCR modulator targets at least one receptor selected from the group consisting of CXCR4 and CCR7.

[2254] 2244. The method of aspect 1990, wherein the method further comprises administering a tumor-specific ion channel modulator.

[2255] 2245. The method of aspect 2244, wherein the ion channel modulator targets a calcium channel.

[2256] 2246. The method of aspect 1990, wherein the method further comprises administering a tumor-specific transporter inhibitor.

[2257] 2247. The method of aspect 2246, wherein the transporter inhibitor targets a glucose transporter.

[2258] 2248. The method of aspect 1990, wherein the method further comprises administering a tumor-specific nuclear receptor modulator.

[2259] 2249. The method of aspect 2248, wherein the nuclear receptor modulator targets at least one receptor selected from the group consisting of androgen receptor (AR) and estrogen receptor (ER).

[2260] 2250. The method of aspect 1990, wherein the method further comprises administering a tumor-specific transcription factor inhibitor.

[2261] 2251. The method of aspect 2250, wherein the transcription factor inhibitor targets at least one transcription factor selected from the group consisting of MYC, HIF-1α, and NF-κB.

[2262] 2252. The method of aspect 1990, wherein the method further comprises administering a tumor-specific epigenetic modulator.

[2263] 2253. The method of aspect 2252, wherein the epigenetic modulator targets at least one enzyme selected from the group consisting of EZH2 and DNMT1.

[2264] 2254. The method of aspect 1990, wherein the method further comprises administering a tumor-specific proteasome activator.

[2265] 2255. The method of aspect 2254, wherein the proteasome activator enhances antigen presentation.

[2266] 2256. The method of aspect 1990, wherein the method further comprises administering a tumor-specific autophagy modulator.

[2267] 2257. The method of aspect 2256, wherein the autophagy modulator inhibits autophagy.

[2268] 2258. The method of aspect 1990, wherein the method further comprises administering a tumor-specific apoptosis inducer.Immorta-ANKC-PCT

[2269] 2259. The method of aspect 2258, wherein the apoptosis inducer is a BH3 mimetic.

[2270] 2260. The method of aspect 1990, wherein the method further comprises administering a tumor-specific necroptosis inducer.

[2271] 2261. The method of aspect 2260, wherein the necroptosis inducer targets RIPK1.

[2272] 2262. The method of aspect 1990, wherein the method further comprises administering a tumor-specific ferroptosis inducer.

[2273] 2263. The method of aspect 2262, wherein the ferroptosis inducer targets GPX4.

[2274] 2264. The method of aspect 1990, wherein the method further comprises administering a tumor-specific pyroptosis inducer.

[2275] 2265. The method of aspect 2264, wherein the pyroptosis inducer targets caspase- 1.

[2276] 2266. The method of aspect 1990, wherein the method further comprises administering a tumor-specific immune cell-recruiting agent.

[2277] 2267. The method of aspect 2266, wherein the immune cell-recruiting agent is a chemokine selected from the group consisting of CCL5, CXCL9, and CXCL10.

[2278] 2268. The method of aspect 1990, wherein the method further comprises administering a tumor-specific cytokine fusion protein.

[2279] 2269. The method of aspect 2268, wherein the cytokine fusion protein includes IL-15.

[2280] 2270. The method of aspect 1990, wherein the method further comprises administering a tumor-specific bispecific T cell engager (BiTE).

[2281] 2271. The method of aspect 2270, wherein the BiTE targets CD3 and a tumor-associated antigen.

[2282] 2272. The method of aspect 1990, wherein the method further comprises administering a tumor-specific trispecific antibody.

[2283] 2273. The method of aspect 2272, wherein the trispecific antibody targets CD3, a tumor-associated antigen, and an NK cell receptor.

[2284] 2274. The method of aspect 1990, wherein the method further comprises administering a tumor-specific antibody-dependent cell-mediated cytotoxicity (ADCC) enhancer.Immorta-ANKC-PCT

[2285] 2275. The method of aspect 2274, wherein the ADCC enhancer is an antiCD 16 antibody.

[2286] 2276. The method of aspect 1990, wherein the method further comprises administering a tumor-specific complement-dependent cytotoxicity (CDC) enhancer.

[2287] 2277. The method of aspect 2276, wherein the CDC enhancer is an antiCD 55 antibody.

[2288] 2278. The method of aspect 1990, wherein the method further comprises administering a tumor-specific immune cell-editing agent.

[2289] 2279. The method of aspect 2278, wherein the immune cell-editing agent uses CRISPR to enhance dendritic cell function.

[2290] 2280. The method of aspect 1990, wherein the method further comprises administering a tumor-specific immune cell-reprogramming agent.

[2291] 2281. The method of aspect 2280, wherein the immune cell -reprogramming agent converts M2 macrophages to Ml macrophages.

[2292] 2282. The method of aspect 1990, wherein the method further comprises administering a tumor-specific immune cell-trafficking agent.

[2293] 2283. The method of aspect 2282, wherein the immune cell-trafficking agent enhances dendritic cell homing to the tumor.

[2294] 2284. The method of aspect 1990, wherein the method further comprises administering a tumor-specific immune cell-survival agent.

[2295] 2285. The method of aspect 2284, wherein the immune cell-survival agent is an anti-apoptotic protein.

[2296] 2286. The method of aspect 1990, wherein the method further comprises administering a tumor-specific immune cell-proliferation agent.

[2297] 2287. The method of aspect 2286, wherein the immune cell-proliferation agent is a growth factor.

[2298] 2288. The method of aspect 1990, wherein the method further comprises administering a tumor-specific immune cell-differentiation agent.

[2299] 2289. The method of aspect 2288, wherein the immune cell-differentiation agent promotes dendritic cell differentiation.

[2300] 2290. The method of aspect 1990, wherein the method further comprises administering a tumor-specific immune cell-activation agent.

[2301] 2291. The method of aspect 2290, wherein the immune cell-activation agent is a CD40 agonist.Immorta-ANKC-PCT

[2302] 2292. The method of aspect 1990, wherein the method further comprises administering a tumor-specific immune cell-exhaustion inhibitor.

[2303] 2293. The method of aspect 2292, wherein the immune cell-exhaustion inhibitor targets LAG-3.

[2304] 2294. The method of aspect 1990, wherein the method further comprises administering a tumor-specific immune cell-senescence inhibitor.

[2305] 2295. The method of aspect 2294, wherein the immune cell-senescence inhibitor targets p16.

[2306] 2296. The method of aspect 1990, wherein the method further comprises administering a tumor-specific immune cell-metabolism modulator.

[2307] 2297. The method of aspect 2296, wherein the immune cell-metabolism modulator enhances dendritic cell glycolysis.

[2308] 2298. The method of aspect 1990, wherein the method further comprises administering a tumor-specific immune cell-signaling modulator.

[2309] 2299. The method of aspect 2298, wherein the immune cell-signaling modulator enhances dendritic cell receptor signaling.

[2310] 2300. The method of aspect 1990, wherein the method further comprises administering a tumor-specific immune cell-adhesion modulator.

[2311] 2301. The method of aspect 2300, wherein the immune cell-adhesion modulator enhances dendritic cell adhesion to tumor cells.

[2312] 2302. The method of aspect 1990, wherein the method further comprises administering a tumor-specific immune cell-migration modulator.

[2313] 2303. The method of aspect 2302, wherein the immune cell-migration modulator enhances dendritic cell migration to the tumor.

[2314] 2304. The method of aspect 1990, wherein the method further comprises administering a tumor-specific immune cell-cytotoxicity enhancer.

[2315] 2305. The method of aspect 2304, wherein the immune cell-cytotoxicity enhancer increases perforin expression in NK cells.

[2316] 2306. The method of aspect 1990, wherein the method further comprises administering a tumor-specific immune cell-memory inducer.

[2317] 2307. The method of aspect 2306, wherein the immune cell -memory inducer promotes memory T cell formation.

[2318] 2308. The method of aspect 1990, wherein the method further comprises administering a tumor-specific immune cell-stemness modulator.Immorta-ANKC-PCT

[2319] 2309. The method of aspect 2308, wherein the immune cell-stemness modulator enhances dendritic cell stemness.

[2320] 2310. The method of aspect 1990, wherein the method further comprises administering a tumor-specific immune cell-plasticity modulator.

[2321] 2311. The method of aspect 2310, wherein the immune cell-plasticity modulator enhances dendritic cell plasticity.

[2322] 2312. The method of aspect 1990, wherein the method further comprises administering a tumor-specific immune cell-epigenetic modulator.

[2323] 2313. The method of aspect 2312, wherein the immune cell-epigenetic modulator enhances dendritic cell effector function.

[2324] 2314. The method of aspect 1990, wherein the method further comprises administering a tumor-specific immune cell-transcriptional regulator.

[2325] 2315. The method of aspect 2314, wherein the immune cell-transcriptional regulator enhances dendritic cell gene expression.

[2326] 2316. The method of aspect 1990, wherein the method further comprises administering a tumor-specific immune cell-post-tra...

Claims

Immorta-ANKC-PCTClaims1. A method of increasing natural killer cell activity in an animal comprising administration of one or more senolytic agents.

2. The method of claim 1, wherein said natural killer cell activity is ability of a natural killer cell to induce lysis of a neoplastically transformed cell.

3. The method of claim 2, wherein said neoplastically transformed cell expresses reduced MHC I and / or enhanced expression of NK activatory ligands.

4. The method of claim 3, wherein said NK activatory ligands are selected from a group consisting of: a) MICA / MICB; b) ULBP1; c) CD155; d) B7H6; and e) CD48, and combinations thereof.

5. The method of claim 1, wherein said senolytic agent is an inhibitor of BCL-2.

6. The method of claim 1, wherein said senolytic agent is selected from a group consisting of: Dasatinib, Quercetin, Fisetin, Navitoclax (ABT-263), A1331852,A1155463, ABT-737, 17-DMAG (alvespimycin), Geldanamycin, Tanespimycin (17-AAG), Piperlongumine, Luteolin, Curcumin, Curcumin analog EF24, Procyanidin Cl, EGCG (epigallocatechin gallate), Resveratrol, Apigenin, Kaempferol, Naringenin, Phloretin, Oleuropein, Hydroxytyrosol, Digoxin, Proscillaridin A, Digitoxin, Azithromycin, Roxithromycin, HSP90 inhibitors (general class), BCL-2 family inhibitors (general), F0X04-DRI, UBX0101, UBX1967, SSK1, Ruxolitinib (senomorphic overlap noted in some contexts), Berberine, Rutin, Catechin, Proanthocyanidin, Ginkgo biloba extract (EGb 761), Theaflavins, Gamma-tocotrienols, Spermidine, Urolithin A, Panaxatriol, Voclosporin, Idarubicin, Quisinostat, Bufotalidin, Cymarin, and Helveticoside, and combinations thereof.

7. The method of claim 1, wherein said senolytic agent is an immunotherapy.

8. The method of claim 7, wherein said immunotherapy is a bispecific antibody.

9. The method of claim 8, wherein said bispecific antibody engages a senescent-specific and / or senescence associated antigen with anti-CD3.Immorta-ANKC-PCT10. The method of claim 7, wherein said senolytic immunotherapy is one or more senescence associated peptides administered in an immunogenic manner to the recipient.

11. A composition capable of activating NK cells comprising autologous dendritic cells (DCs) pulsed with a lysate derived from senescent cells, wherein the senescent cells are autologous or syngeneic fibroblasts induced to senescence, and wherein the pulsed DCs express at least one senescence-associated antigen and upregulated co-stimulatory molecules selected from the group consisting of: CD80, CD86, and MHC class II.

12. The composition of claim 11, wherein the lysate is prepared by subjecting the senescent fibroblasts to at least three cycles of freeze-thaw lysis, followed by centrifugation to obtain a soluble supernatant containing senescence-associated antigens including p16INK4a.

13. The composition of claim 11 or 12, wherein the dendritic cells are bone marrow-derived or monocyte-derived DCs differentiated in the presence of GM-CSF and IL-4, and pulsed with the senescent cell lysate at a ratio of approximately 1:10 (DC to lysate protein equivalent) for about 24 hours in the presence of a maturation stimulus.

14. A method of generating a senolytic immunotherapy capable of increasing NK activity, comprising: (a) isolating and differentiating autologous dendritic cells; (b) inducing senescence in autologous fibroblasts and preparing a lysate therefrom; (c) pulsing the dendritic cells with the senescent cell lysate; and (d) harvesting the pulsed dendritic cells as a vaccine formulation.

15. The method of claim 14, wherein said NK cells express CD56 and in an activated state produce more interferon gamma as compared to NK cells in a non-activated state.

16. The method of claim 14, wherein said NK cells express CD56 and in an activated state produce more BDNF as compared to NK cells in a non-activated state.

17. A method of increasing activity of NK cells in a host by administration of a small molecule senolytic agent.

18. The method of claim 17, wherein said agent is dasatinib.Immorta-ANKC-PCT19. The method of claim 17, wherein said NK activity is stimulation of dendritic cell maturation.

20. The method of claim 19, wherein said dendritic cell maturation is increased expression of CD80 and / or CD86.

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