Senescent cell targeting t cell responses by ex VIVO generated antigen presenting cells

Abstract

Methods for treating a cancer patient comprising initiating or increasing memory immune responses to senescent cells and / or antigens from senescent cells. Methods for pulsing antigen presenting cells (e.g., dendritic cells) with one or more senescence associated antigens generated in vitro, wherein said senescence associated antigens are capable of inducing maturation of said antigen presenting cells. Specific induction of immunity to cancer by inducing immunity against senescent cells in a cancer patient. Methods of inducing immunity against cancer in a subject using an antigen presenting cell such as a dendritic cell, wherein the dendritic cell is pulsed with lysate from a senescent cell. Antigen presenting cell comprising dendritic cells, B cells, endothelial cells, or neutrophils are pulsed with one or a plurality of senescence-associated antigens. Methods for generating one or a plurality of senescence-associated antigens from senescent fibroblasts that are cultured under stress such as oxidative stress.

Description

SENESCENT CELL TARGETING T CELL RESPONSES BY EX VIVOGENERATED ANTIGEN PRESENTING CELLSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims priority to and benefit from U.S. Provisional Application No. 63 / 637,306 titled “SENESCENT CELL TARGETING T CELL RESPONSES BY EX VIVO GENERATED ANTIGEN PRESENTING CELLS” filed on April 22, 2024, the entire contents of which are hereby incorporated by reference.FIELD OF THE INVENTION

[0002] The invention relates to the field of oncology. More specifically, the invention relates to therapeutic approaches utilizing cellular vaccines to modify the tumor microenvironment by targeting senescent cells that accumulate in age-related disorders including in cancer.BACKGROUND

[0003] Cancer is the second biggest cause of morbidity and mortality. For example, lung cancer is the number one cause of cancer mortality globally and has an estimated incidence of 1.3 million new cases every year. In the USA, lung cancer deaths per annum are higher than breast cancer, colon cancer, and melanoma combined [1], Approximately 80-85% of the newly diagnosed cases of lung cancer are non-small cell lung cancer (NSCLC) (adenocarcinoma, squamous carcinoma, and large cell carcinoma), and 15-20% are small cell lung carcinoma. In the majority of cases, patients present with unresectable and / or non-curable disease [2, 3], Locally advanced, good performance status NSCLC patients may be offered concurrent chemotherapy, radical radiotherapy, and / or surgery, with a resultant 8-month progression-free survival rate and <15% 5-year survival [4], Patients diagnosed with metastatic disease receive newer cytotoxic chemotherapies such as pemetrexed [17-month median overall survival (OS)] and treatment with molecularly targeted therapeutics for adenocarcinomas, such as next generation small molecules targeting the EGFR (24 months median OS) and ALK inhibitors (20 months median OS). Thus, the survival rate for advanced disease has improved only marginally [5-7], In the last decade, there has been a better understanding of how cancer interacts with the immune cells and the ways that the cancer have developed to evade the immune system,resulting in a new era of cancer immunotherapy protocols, which may aid in overcoming the limitations of conventional therapeutic strategies [8-21],

[0004] Although recent treatment advances for lung cancer have led to increased disease-free and overall survival rates, the majority of patients recur, and survival curves show no signs of a plateau associated with disease cure, indicating persistence of occult microscopic disease that ultimately leads to morbidity and mortality. The immune system is uniquely suited to “search out and destroy” this occult disease, thus providing a basis for the promise of anti-tumor immunotherapy. Studies of adoptive T cell immunotherapy

[0022] , along with recently reported positive clinical results in non-Hodgkins lymphoma [23, 24] and prostate cancer immunotherapy targeting tumor-associated antigens (TAAs), have provided proof of concept that the immune system can support a clinically effective anti-tumor immune response. Although the benefits of anti-tumor immunotherapy have not been demonstrated in a wide range of tumor types, it has been postulated that the missing critical element is a sufficiently potent, readily translatable cancer vaccine strategy

[0025] , Patients with lung cancer can have endogenous or immunotherapy elicited humoral and cellular responses to several tumor-associated antigens (TAAs) [26-28], However, these have generally been of sub-optimal magnitude with elusive clinical efficacy. It is interesting that the actual process of carcinogenesis may be intimately associated with the induction of tumor antigenicity. For example, Hopewell et al. showed that NF-kappa B, a transcription factor classically associated with inflammation and found upregulated in lung cancer, appears to stimulate T cell responsiveness to lung cancer. Using a global RNA expression microarray, they showed that NF-KB enhanced expression of several T cell chemokines, including CCL2, and decreased CCL2 expression was associated with enhanced tumor growth in a mouse lung cancer model. However, in the clinical situation, NF-KB function in human lung tumors, they identified a gene expression signature in human lung adenocarcinoma cell lines that was associated with NF-KB activity level. In patient tumor samples, overall lung tumor NF-KB activity was strongly associated with T cell infiltration but not with cancer cell proliferation

[0029] ,

[0005] A variety of TAAs have been identified in lung cancer consisting of overexpressed normal proteins and mutated proteins that are normally found in pulmonary tissue, however, only a minority of the TAAs that have been discovered so far are immunogenic, which limits the potential use for immunotherapy. In addition, whilethe overwhelming majority of TAAs are expressed in tumor cells, they are typically also expressed in a variety of normal cells, e.g. the lung cancer TAAs; epidermal growth factor receptors (HER2), carcinoembryonic antigen (CEA), mucin (MUC1), the tumor suppressor protein p53, and telomerase reverse transcriptase (TERT). Thus, they are recognized by the immune system as self-molecules, and the immune system has protective mechanisms for preventing recognition of self-tissue antigens and autoimmune responses. Additionally, tumors employ other mechanisms for escaping immune surveillance, such as: (i) low level expression of MHC class I molecules

[0030] ; (ii) lack of expression of B7 (CD80 / CD86) co-stimulatory molecules

[0031] ; (iii) production of cytokines that stimulate the accumulation of immune-suppressor cells [32, 33]; and (iv) ineffective processing and presentation of self-antigens by “professional” antigen- presenting cells (APC)

[0034] , This probably explains why TAA or tumor cell vaccines that have been used in clinical trials generally do not induce strong protective immunity

[0022] , Identification of novel TAA that are not expressed on normal cells may provide an attractive alternative, particularly if combined with potent immunotherapeutic platforms, because these antigens are less likely to be subject to the tolerogenic mechanisms that limit immune responses to “self’ antigens and therefore, may be better immunogens.

[0006] To date, little progress has been made in advancing the survival of cancer patients. The current invention provides means of overcoming the shortcomings of current oncology therapies, in part through immunological removal of senescent cells.SUMMARY

[0007] Methods for treating a subject with cancer are provided, wherein the method comprises initiating or increasing memory immune responses to senescent cells and / or antigens derived from senescent cells are disclosed. Methods are provided for pulsing antigen presenting cells such as immature dendritic cells with one or a plurality senescence associated antigens generated in vitro, wherein said senescence associated antigens have the properties of inducing maturation of said antigen presenting cells. In certain embodiments, specific induction of immunity to cancer is achieved by induction of immunity against senescent cells in a subject in need thereof. Embodiments are disclosed for inducing immunity against cancer in a subject using an antigen presenting cell such as a dendritic cell, wherein the dendritic cell is pulsed with a cancer-associated antigen or peptide, and wherein the cancer-associated antigen or peptide is associatedwith cellular senescence. In certain embodiments, antigen presenting cell comprising dendritic cells, B cells, endothelial cells, macrophages, myeloid cells, mesenchymal cells, lymphocytes or neutrophils are pulsed with one or a plurality of senescence-associated antigens. Methods are also disclosed for obtaining and utilizing one or a plurality of senescence-associated antigens from senescent fibroblasts that are cultured under conditions of cellular stress, such as oxidative stress, wherein the one or plurality of senescence-associated antigens are used to stimulate anti -turn or immunity in a subject in need thereof.

[0008] Various aspects of the invention are enumerated in the following paragraphs:

[0009] Aspect 1 : A method of inducing immunity to senescence cells comprising the steps of: a) obtaining a cell population to be made senescent; b) treating said population with one or more senescence inducing agents; c) providing one or more cellular stressors to said cell prior to, and / or, concurrent with, and / or subsequent to exposure to said one or more senescence promoting agents; and d) using said senescent cell exposed to said cellular stressors as a source of antigenic materials.

[0010] Aspect 2: The method of Aspect 1, wherein said cell population to be made senescent is a population characterized by propensity for in vivo senescence.

[0011] Aspect 3: The method of Aspect 1, wherein said cell population to be made senescent is a fibroblast population.

[0012] Aspect 4: The method of Aspect 3, wherein said fibroblast population is derived from one or a plurality of tissue sources comprising: a) skin; b) foreskin; c) placenta; d) umbilical cord; e) Wharton’s Jelly; f) bone marrow; g) adipose tissue; and h) peripheral blood.

[0013] Aspect 5: The method of Aspect 3, wherein said fibroblast population is derived from the periphery of a tumor.

[0014] Aspect 6: The method of Aspect 3, wherein said fibroblast population is derived from the periphery of a keloid.

[0015] Aspect 7: The method of Aspect 3, wherein said fibroblast population is derived from amniotic fluid.

[0016] Aspect 8: The method of Aspect 3, wherein said fibroblast population is derived from amniotic membrane.

[0017] Aspect 9: The method of Aspect 3, wherein said fibroblast population is derived from omental tissue.

[0018] Aspect 10: The method of Aspect 3, wherein said fibroblast population is derived from endometrial tissue.

[0019] Aspect 11 : The method of Aspect 3, wherein said fibroblast expresses CD11c.

[0020] Aspect 12: The method of Aspect 3, wherein said fibroblast expresses c-kit.

[0021] Aspect 13: The method of Aspect 3, wherein said fibroblast expresses c-met.

[0022] Aspect 14: The method of Aspect 3, wherein said fibroblast expresses OCT4.

[0023] Aspect 15: The method of Aspect 3, wherein said fibroblast expressesNANOG.

[0024] Aspect 16: The method of Aspect 3, wherein said fibroblast expresses KLF4.

[0025] Aspect 17: The method of Aspect 3, wherein said fibroblast expresses SSEA4.

[0026] Aspect 18: The method of Aspect 3, wherein said fibroblast expresses TRA-1.

[0027] Aspect 19: The method of Aspect 3, wherein said fibroblast expresses PIM-1.

[0028] Aspect 20: The method of Aspect 3, wherein said fibroblast expresses PDGF- receptor.

[0029] Aspect 21 : The method of Aspect 3, wherein said fibroblast expresses SLC14A4.

[0030] Aspect 22: The method of Aspect 3, wherein said fibroblast is cultured under conditions stimulating expression of HL A genes.

[0031] Aspect 23: The method of Aspect 22, wherein said condition stimulating expression of HLA genes is exposure to one or more agents capable of stimulating MAPK / p38.

[0032] Aspect 24: The method of Aspect 22, wherein said condition stimulating expression of HLA genes is exposure to one or more agents capable of stimulating NF- kappa B.

[0033] Aspect 25: The method of Aspect 22, wherein said condition stimulating expression of HLA genes is exposure to phenylbutyrate.

[0034] Aspect 26: The method of Aspect 25, wherein said condition stimulating expression of HLA genes is exposure to phenylbutyrate at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 25% compared to baseline.

[0035] Aspect 27: The method of Aspect 25, wherein said condition stimulating expression of HLA genes is exposure to phenylbutyrate at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 50% compared to baseline.

[0036] Aspect 28: The method of Aspect 25, wherein said condition stimulating expression of HLA genes is exposure to phenylbutyrate at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 100% compared to baseline.

[0037] Aspect 29: The method of Aspect 22, wherein said condition stimulating expression of HLA genes is exposure to valproic acid.

[0038] Aspect 30: The method of Aspect 29, wherein said condition stimulating expression of HLA genes is exposure to phenylbutyrate at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 25% compared to baseline.

[0039] Aspect 31 : The method of Aspect 29, wherein said condition stimulating expression of HLA genes is exposure to phenylbutyrate at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 50% compared to baseline.

[0040] Aspect 32: The method of Aspect 29, wherein said condition stimulating expression of HLA genes is exposure to phenylbutyrate at a concentration and durationsufficient to increase expression of the interferon gamma receptor by at least 100% compared to baseline.

[0041] Aspect 33: The method of Aspect 22, wherein said condition stimulating expression of HLA genes is exposure to trichostatin A.

[0042] Aspect 34: The method of Aspect 33, wherein said condition stimulating expression of HLA genes is exposure to phenylbutyrate at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 25% compared to baseline.

[0043] Aspect 35: The method of Aspect 33, wherein said condition stimulating expression of HLA genes is exposure to trichostatin A at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 50% compared to baseline.

[0044] Aspect 36: The method of Aspect 33, wherein said condition stimulating expression of HLA genes is exposure to trichostatin A at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 100% compared to baseline.

[0045] Aspect 37: The method of Aspect 22, wherein said condition stimulating expression of HLA genes is exposure to interferon gamma.

[0046] Aspect 38: The method of Aspect 37, wherein said condition stimulating expression of HLA genes is exposure to interferon gamma at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 25% compared to baseline.

[0047] Aspect 39: The method of Aspect 37, wherein said condition stimulating expression of HLA genes is exposure to interferon gamma at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 50% compared to baseline.

[0048] Aspect 40: The method of Aspect 37, wherein said condition stimulating expression of HLA genes is exposure to interferon gamma at a concentration and durationsufficient to increase expression of the interferon gamma receptor by at least 100% compared to baseline.

[0049] Aspect 41 : The method of Aspect 22, wherein said condition stimulating expression of HLA genes is exposure to interferon gamma.

[0050] Aspect 42: The method of Aspect 41, wherein said condition stimulating expression of HLA genes is exposure to interferon gamma at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 25% compared to baseline.

[0051] Aspect 43: The method of Aspect 41, wherein said condition stimulating expression of HLA genes is exposure to interferon gamma at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 50% compared to baseline.

[0052] Aspect 44: The method of Aspect 41, wherein said condition stimulating expression of HLA genes is exposure to interferon gamma at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 100% compared to baseline.

[0053] Aspect 45: The method of Aspect 22, wherein said condition stimulating expression of HLA genes comprises exposure to lipopolysaccharide.

[0054] Aspect 46: The method of Aspect 45, wherein said condition stimulating expression of HLA genes is exposure to lipopolysaccharide at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 25% compared to baseline.

[0055] Aspect 47: The method of Aspect 45, wherein said condition stimulating expression of HLA genes is exposure to lipopolysaccharide at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 50% compared to baseline.

[0056] Aspect 48: The method of Aspect 45, wherein said condition stimulating expression of HLA genes is exposure to lipopolysaccharide at a concentration andduration sufficient to increase expression of the interferon gamma receptor by at least 100% compared to baseline.

[0057] Aspect 49: The method of Aspect 22, wherein said condition stimulating expression of HLA genes is exposure to lipopolysaccharide.

[0058] Aspect 50: The method of Aspect 49, wherein said condition stimulating expression of HLA genes is exposure to lipopolysaccharide at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 25% compared to baseline.

[0059] Aspect 51 : The method of Aspect 49, wherein said condition stimulating expression of HLA genes is exposure to lipopolysaccharide at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 50% compared to baseline.

[0060] Aspect 52: The method of Aspect 49, wherein said condition stimulating expression of HLA genes is exposure to lipopolysaccharide at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 100% compared to baseline.

[0061] Aspect 53: The method of Aspect 22, wherein said condition stimulating expression of HLA genes is exposure to beta glucan.

[0062] Aspect 54: The method of Aspect 53, wherein said condition stimulating expression of HLA genes is exposure to beta glucan at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 25% compared to baseline.

[0063] Aspect 55: The method of Aspect 53, wherein said condition stimulating expression of HLA genes is exposure to beta glucan at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 50% compared to baseline.

[0064] Aspect 56: The method of Aspect 53, wherein said condition stimulating expression of HLA genes is exposure to beta glucan at a concentration and durationsufficient to increase expression of the interferon gamma receptor by at least 100% compared to baseline.

[0065] Aspect 57: The method of Aspect 22, wherein said condition stimulating expression of HLA genes is exposure to Poly IC.

[0066] Aspect 58: The method of Aspect 57, wherein said condition stimulating expression of HLA genes is exposure to Poly IC at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 25% compared to baseline.

[0067] Aspect 59: The method of Aspect 57, wherein said condition stimulating expression of HLA genes is exposure to Poly IC at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 50% compared to baseline.

[0068] Aspect 60: The method of Aspect 57, wherein said condition stimulating expression of HLA genes is exposure to Poly IC at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 100% compared to baseline.

[0069] Aspect 61 : The method of Aspect 22, wherein said condition stimulating expression of HLA genes is exposure to interleukin- 17.

[0070] Aspect 62: The method of Aspect 61, wherein said condition stimulating expression of HLA genes is exposure to interleukin- 17at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 25% compared to baseline.

[0071] Aspect 63: The method of Aspect 61, wherein said condition stimulating expression of HLA genes is exposure to interleukin- 17at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 50% compared to baseline.

[0072] Aspect 64: The method of Aspect 61, wherein said condition stimulating expression of HLA genes is exposure to interleukin- 17 at a concentration and durationsufficient to increase expression of the interferon gamma receptor by at least 100% compared to baseline.

[0073] Aspect 65: The method of Aspect 22, wherein said condition stimulating expression of HLA genes is exposure to interleukin- 18.

[0074] Aspect 66: The method of Aspect 61, wherein said condition stimulating expression of HLA genes is exposure to interleukin- 18 at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 25% compared to baseline.

[0075] Aspect 67: The method of Aspect 61, wherein said condition stimulating expression of HLA genes is exposure to interleukin- 18 at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 50% compared to baseline.

[0076] Aspect 68: The method of Aspect 61, wherein said condition stimulating expression of HLA genes is exposure to interleukin- 18 at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 100% compared to baseline.

[0077] Aspect 69: The method of claim 22, wherein said condition stimulating expression of HLA genes is exposure to TRAF3 siRNA.

[0078] Aspect 70: The method of Aspect 69, wherein said condition stimulating expression of HLA genes is exposure to TRAF3 siRNA at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 25% compared to baseline.

[0079] Aspect 71 : The method of Aspect 69, wherein said condition stimulating expression of HLA genes is exposure to TRAF3 siRNA at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 50% compared to baseline.

[0080] Aspect 72: The method of Aspect 69, wherein said condition stimulating expression of HLA genes is exposure to TRAF3 siRNA at a concentration and durationsufficient to increase expression of the interferon gamma receptor by at least 100% compared to baseline.

[0081] Aspect 73: The method of Aspect 22, wherein said condition stimulating expression of HLA genes is exposure to GM-CSF.

[0082] Aspect 74: The method of Aspect 73, wherein said condition stimulating expression of HLA genes is exposure to GM-CSF at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 25% compared to baseline.

[0083] Aspect 75: The method of Aspect 73, wherein said condition stimulating expression of HLA genes is exposure to GM-CSF at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 50% compared to baseline.

[0084] Aspect 76: The method of Aspect 73, wherein said condition stimulating expression of HLA genes is exposure to GM-CSF at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 100% compared to baseline.

[0085] Aspect 77: The method of Aspect 22, wherein said condition stimulating expression of HLA genes is exposure to HMGB1.

[0086] Aspect 78: The method of Aspect 77, wherein said condition stimulating expression of HLA genes is exposure to HMGB1 at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 25% compared to baseline.

[0087] Aspect 79: The method of Aspect 77, wherein said condition stimulating expression of HLA genes is exposure to HMGB1 at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 50% compared to baseline.

[0088] Aspect 80: The method of Aspect 77, wherein said condition stimulating expression of HLA genes is exposure to HMGB1 at a concentration and durationsufficient to increase expression of the interferon gamma receptor by at least 100% compared to baseline.

[0089] Aspect 81 : The method of Aspect 22, wherein said condition stimulating expression of HLA genes is exposure to imiquimod.

[0090] Aspect 82: The method of Aspect 81, wherein said condition stimulating expression of HLA genes is exposure to imiquimod at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 25% compared to baseline.

[0091] Aspect 83: The method of Aspect 81, wherein said condition stimulating expression of HLA genes is exposure to imiquimod at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 50% compared to baseline.

[0092] Aspect 84: The method of Aspect 81, wherein said condition stimulating expression of HLA genes is exposure to imiquimod at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 100% compared to baseline.

[0093] Aspect 85: The method of Aspect 22, wherein said condition stimulating expression of HLA genes is exposure to flagellin.

[0094] Aspect 86: The method of Aspect 85, wherein said condition stimulating expression of HLA genes is exposure to flagellin at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 25% compared to baseline.

[0095] Aspect 87: The method of Aspect 85, wherein said condition stimulating expression of HLA genes is exposure to flagellin at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 50% compared to baseline.

[0096] Aspect 88: The method of Aspect 85, wherein said condition stimulating expression of HLA genes is exposure to flagellin at a concentration and durationsufficient to increase expression of the interferon gamma receptor by at least 100% compared to baseline.

[0097] Aspect 89: The method of Aspect 22, wherein said condition stimulating expression of HLA genes is exposure to belinostat.

[0098] Aspect 90: The method of Aspect 89, wherein said condition stimulating expression of HLA genes is exposure to belinostat at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 25% compared to baseline.

[0099] Aspect 91 : The method of Aspect 89, herein said condition stimulating expression of HLA genes is exposure to belinostat at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 50% compared to baseline.

[0100] Aspect 92: The method of Aspect 89, wherein said condition stimulating expression of HLA genes is exposure to belinostat at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 100% compared to baseline.

[0101] Aspect 93: The method of Aspect 22, wherein said condition stimulating expression of HLA genes is exposure to hydrogen peroxide.

[0102] Aspect 94: The method of Aspect 93, wherein said condition stimulating expression of HLA genes is exposure to hydrogen peroxide at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 25% compared to baseline.

[0103] Aspect 95: The method of Aspect 93, herein said condition stimulating expression of HLA genes is exposure to hydrogen peroxide at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 50% compared to baseline.

[0104] Aspect 96: The method of Aspect 93, wherein said condition stimulating expression of HLA genes is exposure to hydrogen peroxide at a concentration andduration sufficient to increase expression of the interferon gamma receptor by at least 100% compared to baseline.

[0105] Aspect 97: The method of Aspect 22, wherein said condition stimulating expression of HLA genes is exposure to panobinostat.

[0106] Aspect 98: The method of Aspect 97, wherein said condition stimulating expression of HLA genes is exposure to panobinostat at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 25% compared to baseline.

[0107] Aspect 99: The method of Aspect 97, herein said condition stimulating expression of HLA genes is exposure to panobinostat at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 50% compared to baseline.

[0108] Aspect 100: The method of Aspect 97, wherein said condition stimulating expression of HLA genes is exposure to panobinostat at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 100% compared to baseline.

[0109] Aspect 101 : The method of Aspect 22, wherein said condition stimulating expression of HLA genes is exposure to sulforaphane.

[0110] Aspect 102: The method of Aspect 101, wherein said condition stimulating expression of HLA genes is exposure to sulforaphane at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 25% compared to baseline.

[0111] Aspect 103: The method of Aspect 101, herein said condition stimulating expression of HLA genes is exposure to sulforaphane at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 50% compared to baseline.

[0112] Aspect 104: The method of Aspect 101, wherein said condition stimulating expression of HLA genes is exposure to sulforaphane at a concentration and durationsufficient to increase expression of the interferon gamma receptor by at least 100% compared to baseline.

[0113] Aspect 105: The method of Aspect 22, wherein said condition stimulating expression of HLA genes is exposure to vorinostat.

[0114] Aspect 106: The method of Aspect 105, wherein said condition stimulating expression of HLA genes is exposure to vorinostat at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 25% compared to baseline.

[0115] Aspect 107: The method of Aspect 105, herein said condition stimulating expression of HLA genes is exposure to vorinostat at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 50% compared to baseline.

[0116] Aspect 108: The method of Aspect 105, wherein said condition stimulating expression of HLA genes is exposure to vorinostat at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 100% compared to baseline.

[0117] Aspect 109: The method of Aspect 22, wherein said condition stimulating expression of HLA genes is exposure to IL-33.

[0118] Aspect 110: The method of Aspect 109, wherein said condition stimulating expression of HLA genes is exposure to IL-33 at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 25% compared to baseline.

[0119] Aspect 111 : The method of Aspect 109, wherein said condition stimulating expression of HLA genes is exposure to IL-33 at a concentration and duration sufficient to increase expression of the interferon gamma receptor by at least 50% compared to baseline.

[0120] Aspect 112: The method of Aspect 109, wherein said condition stimulating expression of HLA genes is exposure to IL-33 at a concentration and duration sufficientto increase expression of the interferon gamma receptor by at least 100% compared to baseline.

[0121] Aspect 113: The method of Aspect 3, wherein said fibroblast is transfected with one or more immunogenic genes before being induced into a senescent phenotype.

[0122] Aspect 114: The method of Aspect 113, wherein said immunogenic genes encode proteins capable of inducing maturation of dendritic cells.

[0123] Aspect 115: The method of Aspect 114, wherein said induction of dendritic cell maturation is suppressed phagocytic activity.

[0124] Aspect 116: The method of Aspect 114, wherein said induction of dendritic cell maturation is suppressed migratory activity.

[0125] Aspect 117: The method of Aspect 116, wherein said migratory activity is ability to migrate towards a chemotactic gradient.

[0126] Aspect 118: The method of Aspect 117, wherein said chemotactic gradient is a gradient of SDF-1.

[0127] Aspect 119: The method of Aspect 117, wherein said chemotactic gradient is a gradient of interleukin- 1.

[0128] Aspect 120: The method of Aspect 117, wherein said chemotactic gradient is a gradient of interleukin-6.

[0129] Aspect 121 : The method of Aspect 117, wherein said chemotactic gradient is a gradient of interleukin-8.

[0130] Aspect 122: The method of Aspect 117, wherein said chemotactic gradient is a gradient of interleukin-9.

[0131] Aspect 123: The method of Aspect 117, wherein said chemotactic gradient is a gradient of interleukin- 17.

[0132] Aspect 124: The method of Aspect 117, wherein said chemotactic gradient is a gradient of interleukin- 18.

[0133] Aspect 125: The method of Aspect 117, wherein said chemotactic gradient is a gradient of interleukin-21.

[0134] Aspect 126: The method of Aspect 117, wherein said chemotactic gradient is a gradient of interleukin-23.

[0135] Aspect 127: The method of Aspect 117, wherein said chemotactic gradient is a gradient of interleukin-27.

[0136] Aspect 128: The method of Aspect 117, wherein said chemotactic gradient is a gradient of TNF-alpha.

[0137] Aspect 129: The method of Aspect 117, wherein said chemotactic gradient is a gradient of lymphotoxin.

[0138] Aspect 130: The method of Aspect 117, wherein said chemotactic gradient is a gradient of osteopontin.

[0139] Aspect 131 : The method of Aspect 114, wherein said dendritic cell maturation is enhanced ability of said dendritic cells to induce proliferation of allogeneic T cells.

[0140] Aspect 132: The method of Aspect 131, wherein said proliferation of said allogeneic T cells is performed in a mixed lymphocyte reaction.

[0141] Aspect 133: The method of Aspect 132, wherein said mixed lymphocyte reaction is contact dependent.

[0142] Aspect 134: The method of Aspect 131, wherein said dendritic cell maturation is enhanced ability of said dendritic cells to produce cytokines.

[0143] Aspect 135: The method of Aspect 134, wherein said cytokine is interferon alpha.

[0144] Aspect 136: The method of Aspect 134, wherein said cytokine is interferon gamma.

[0145] Aspect 137: The method of Aspect 134, wherein said cytokine is interleukin-1 beta.

[0146] Aspect 138: The method of Aspect 134, wherein said cytokine is interleukin-2.

[0147] Aspect 139: The method of Aspect 134, wherein said cytokine is interleukin-3.

[0148] Aspect 140: The method of Aspect 134, wherein said cytokine is interleukin-4.

[0149] Aspect 141 : The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of CD la.

[0150] Aspect 142: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of CD11c.

[0151] Aspect 143: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of CD40.

[0152] Aspect 144: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of CD44.

[0153] Aspect 145: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of CD48.

[0154] Aspect 146: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of CXCL1.

[0155] Aspect 147: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of CXCL2.

[0156] Aspect 148: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of IL-18R1.

[0157] Aspect 149: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of IL-18RAP.

[0158] Aspect 150: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of IL-1 A.

[0159] Aspect 151 : The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of IL-1RAP.

[0160] Aspect 152: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of IRF8.

[0161] Aspect 153: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of JAK2.

[0162] Aspect 154: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of MAP3K8.

[0163] Aspect 155: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of MAP4K4.

[0164] Aspect 156: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of MAPK4.

[0165] Aspect 157: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of MMP19.

[0166] Aspect 158: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of NF-kB2.

[0167] Aspect 159: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of NFKBIZ.

[0168] Aspect 160: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of TNFRSF18.

[0169] Aspect 161 : The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of IKBKA.

[0170] Aspect 162: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of TNFRSF2.

[0171] Aspect 163: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of TNFRSF4.

[0172] Aspect 164: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of TNFRSF7.

[0173] Aspect 165: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of TNFSF9.

[0174] Aspect 166: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of CCL2.

[0175] Aspect 167: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of CCL3.

[0176] Aspect 168: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of CCL4.

[0177] Aspect 169: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of CCL5.

[0178] Aspect 170: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of CCL8.

[0179] Aspect 171 : The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of CCL19.

[0180] Aspect 172: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of CXCL1.

[0181] Aspect 173: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of CXCL2.

[0182] Aspect 174: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of CXCL9.

[0183] Aspect 175: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of CXCL10.

[0184] Aspect 176: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of CXCL11.

[0185] Aspect 177: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of CCR7.

[0186] Aspect 178: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of CXCR4.

[0187] Aspect 179: The method of Aspect 114, wherein said dendritic cell maturation is associated with increased expression of CXCR4.

[0188] Aspect 180: A method of inducing immunity to cancer comprising the steps of: a) obtaining a source of cancer cells; b) isolating cancer antigens from said cancer cells; c) using said cancer antigens to pulse a population of antigen presenting cells; d) concurrently pulsing said population of said antigen presenting cells with one or more sources of senescent cell antigens; and e) administering said antigen presenting cells to said patient with cancer.

[0189] Aspect 181 : The method of Aspect 180, wherein said lung cancer antigens are selected from a group comprising of: CEA, SCC, CYFRA21-1, SLX and CAI 9-9.

[0190] Aspect 182: The method of Aspect 180, wherein said lung cancer antigens are isolated from a lung cancer cell line.

[0191] Aspect 183: The method of Aspect 182, wherein said lung cancer cell line is a lung cancer stem cell line.

[0192] Aspect 184: The method of Aspect 183, wherein said lung cancer stem cell line is immortal.

[0193] Aspect 185: The method of Aspect 184, wherein said lung cancer stem cell line has been immortalized by transfection with hTERT.

[0194] Aspect 186: The method of Aspect 184, wherein said lung cancer stem cell line has been immortalized by transfection with NANOG.

[0195] Aspect 187: The method of Aspect 184, wherein said lung cancer stem cell line has been immortalized by transfection with RelB.

[0196] Aspect 188: The method of Aspect 184, wherein said lung cancer stem cell line has been immortalized by transfection with NF -kappa B.

[0197] Aspect 189: The method of Aspect 184, wherein said lung cancer stem cell line has been immortalized by fusion with a hematopoietic stem cell or a cell with hematopoietic potential.

[0198] Aspect 190: The method of Aspect 189, wherein said cells with said hematopoietic potential express CD34.

[0199] Aspect 191 : The method of Aspect 189, wherein said cells with said hematopoietic potential express CD 133.

[0200] Aspect 192: The method of Aspect 189, wherein said cells with said hematopoietic potential express leukemia inhibitory factor receptor.

[0201] Aspect 193: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of CXCR4 by 25% or more when cultured in the presence of interleukin-3.

[0202] Aspect 194: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of CXCR4 by 50% or more when cultured in the presence of interleukin-3.

[0203] Aspect 195: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of CXCR4 by 200% or more when cultured in the presence of interleukin-3.

[0204] Aspect 196: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of CXCR4 by 25% or more when cultured in the presence of interleukin-7.

[0205] Aspect 197: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of CXCR4 by 50% or more when cultured in the presence of interleukin-7.

[0206] Aspect 198: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of CXCR4 by 200% or more when cultured in the presence of interleukin-7.

[0207] Aspect 199: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of CXCR4 by 25% or more when cultured in the presence of steel factor.

[0208] Aspect 200: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of CXCR4 by 50% or more when cultured in the presence of steel factor.

[0209] Aspect 201 : The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of CXCR4 by 200% or more when cultured in the presence of steel factor.

[0210] Aspect 202: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of CXCR4 by 25% or more when cultured in the presence of interleukin-35.

[0211] Aspect 203: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of CXCR4 by 50% or more when cultured in the presence of interleukin-35.

[0212] Aspect 204: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of CXCR4 by 200% or more when cultured in the presence of interleukin-35.

[0213] Aspect 205: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of CXCR4 by 25% or more when cultured in the presence of interleukin-38.

[0214] Aspect 206: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of CXCR4 by 50% or more when cultured in the presence of interleukin-38.

[0215] Aspect 207: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of CXCR4 by 200% or more when cultured in the presence of interleukin-38.

[0216] Aspect 208: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of c-kit by 25% or more when cultured in the presence of interleukin-3.

[0217] Aspect 209: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of c-kit by 50% or more when cultured in the presence of interleukin-3.

[0218] Aspect 210: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of c-kit by 200% or more when cultured in the presence of interleukin-3.

[0219] Aspect 211 : The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of c-kit by 25% or more when cultured in the presence of interleukin-7.

[0220] Aspect 212: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of c-kit by 50% or more when cultured in the presence of interleukin-7.

[0221] Aspect 213: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of c-kit by 200% or more when cultured in the presence of interleukin-7.

[0222] Aspect 214: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of c-kit by 25% or more when cultured in the presence of steel factor.

[0223] Aspect 215: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of c-kit by 50% or more when cultured in the presence of steel factor.

[0224] Aspect 216: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of c-kit by 200% or more when cultured in the presence of steel factor.

[0225] Aspect 217: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of c-kit by 25% or more when cultured in the presence of interleukin-35.

[0226] Aspect 218: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of c-kit by 50% or more when cultured in the presence of interleukin-35.

[0227] Aspect 219: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of c-kit by 200% or more when cultured in the presence of interleukin-35.

[0228] Aspect 220: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of c-kit by 25% or more when cultured in the presence of interleukin-38.

[0229] Aspect 221 : The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of c-kit by 50% or more when cultured in the presence of interleukin-38.

[0230] Aspect 222: The method of Aspect 189, wherein said cells with said hematopoietic potential increase expression of c-kit by 200% or more when cultured in the presence of interleukin-38.

[0231] Aspect 223: The method of Aspect 180, wherein a regenerative adjuvant is added to the combination of antigen presenting cells, senescent antigens and / or lung tumor peptide in order to enhance efficacy of antigen presentation.

[0232] Aspect 224: The method of Aspect 223, wherein said regenerative adjuvant is platelet rich plasma.

[0233] Aspect 225: The method of Aspect 223, wherein said regenerative adjuvant is fibrin rich plasma.

[0234] Aspect 226: The method of Aspect 223, wherein said regenerative adjuvant is one or more growth factors.

[0235] Aspect 227 : The method of Aspect 226, wherein said growth factor is FGF 1.

[0236] Aspect 228: The method of Aspect 226, wherein said growth factor is FGF2.

[0237] Aspect 229: The method of Aspect 226, wherein said growth factor is FGF5.

[0238] Aspect 230: The method of Aspect 226, wherein said growth factor is VEGF.

[0239] Aspect 231 : The method of Aspect 226, wherein said growth factor is VEGF-C.

[0240] Aspect 232: The method of Aspect 226, wherein said growth factor is HGF.

[0241] Aspect 233 : The method of Aspect 226, wherein said growth factor is chorionic gonadotrophin.

[0242] Aspect 234: The method of Aspect 226, wherein said growth factor is FGF 1.

[0243] Aspect 235: The method of Aspect 223, wherein said regenerative adjuvant is administration of an autologous stem cell transplant.

[0244] Aspect 236: The method of Aspect 235, wherein said autologous stem cell transplant is performed using bone marrow stem cells.

[0245] Aspect 237: The method of Aspect 236, wherein said bone marrow stem cells are bone marrow mononuclear cells.

[0246] Aspect 238: The method of Aspect 236, wherein said bone marrow stem cells are bone marrow CD34 positive cells.

[0247] Aspect 239: The method of Aspect 236, wherein said bone marrow stem cells are bone marrow CD33 positive cells.

[0248] Aspect 240: The method of Aspect 236, wherein said bone marrow stem cells are bone marrow CD133 positive cells.

[0249] Aspect 241 : The method of Aspect 236, wherein said bone marrow stem cells are bone marrow CD 105 positive cells.

[0250] Aspect 242: The method of Aspect 236, wherein said bone marrow stem cells are bone marrow CD73 positive cells.

[0251] Aspect 243: The method of Aspect 236, wherein said bone marrow stem cells are bone marrow c-kit positive cells.

[0252] Aspect 244: The method of Aspect 236, wherein said bone marrow stem cells are bone marrow c-met positive cells.

[0253] Aspect 245: The method of Aspect 236, wherein said bone marrow stem cells are bone marrow FGF-2 receptor positive cells.

[0254] Aspect 246: The method of Aspect 236, wherein said bone marrow stem cells are bone marrow HLA-G positive cells.

[0255] Aspect 247: The method of Aspect 236, wherein said bone marrow stem cells are bone marrow aldehyde dehydrogenase expressing cells.

[0256] Aspect 248: The method of Aspect 236, wherein said bone marrow stem cells are bone marrow indolamine-2, 3 -dioxygenase expressing cells.

[0257] Aspect 249: The method of Aspect 236, wherein said bone marrow stem cells are bone marrow VSEL cells.

[0258] Aspect 250: The method of Aspect 236, wherein said bone marrow stem cells are bone marrow myeloid derived suppressor cells.

[0259] Aspect 251 : The method of Aspect 235, wherein said autologous stem cell transplant is performed using a regenerative adjuvant in addition to said bone marrow cells.

[0260] Aspect 252: The method of Aspect 251, wherein said regenerative adjuvant is treatment with a medical device.

[0261] Aspect 253: The method of Aspect 252, wherein said medical device administers low level irradiation to said bone marrow cells prior to administration of said cells into said patient.

[0262] Aspect 254: The method of Aspect 253, wherein said low level irradiation is near infrared irradiation.

[0263] Aspect 255: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 25% proliferation of said stem cells over the period of 72 hours.

[0264] Aspect 256: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 50% proliferation of said stem cells over the period of 72 hours.

[0265] Aspect 257: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 100% proliferation of said stem cells over the period of 72 hours.

[0266] Aspect 258: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 25% production of interleukin- 10 from said stem cells over the period of 72 hours.

[0267] Aspect 259: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 50% production of interleukin- 10 from said stem cells over the period of 72 hours.

[0268] Aspect 260: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 100% production of interleukin- 10 from said stem cells over the period of 72 hours.

[0269] Aspect 261 : The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 25% production of interleukin- 13 from said stem cells over the period of 72 hours.

[0270] Aspect 262: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 50% production of interleukin- 13 from said stem cells over the period of 72 hours.

[0271] Aspect 263 : The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 100% production of interleukin- 13 from said stem cells over the period of 72 hours.

[0272] Aspect 264: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 25% production of interleukin-20 from said stem cells over the period of 72 hours.

[0273] Aspect 265: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 50% production of interleukin-20 from said stem cells over the period of 72 hours.

[0274] Aspect 266: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 100% production of interleukin-20 from said stem cells over the period of 72 hours.

[0275] Aspect 267: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 25% production of interleukin-22 from said stem cells over the period of 72 hours.

[0276] Aspect 268: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 50% production of interleukin-22 from said stem cells over the period of 72 hours.

[0277] Aspect 269: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 100% production of interleukin-22 from said stem cells over the period of 72 hours.

[0278] Aspect 270: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 25% production of interleukin-25 from said stem cells over the period of 72 hours.

[0279] Aspect 271 : The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 50% production of interleukin-25 from said stem cells over the period of 72 hours.

[0280] Aspect 272: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 100% production of interleukin-25 from said stem cells over the period of 72 hours.

[0281] Aspect 273 : The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 25% production of interleukin-35 from said stem cells over the period of 72 hours.

[0282] Aspect 274: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 50% production of interleukin-35 from said stem cells over the period of 72 hours.

[0283] Aspect 275: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 100% production of interleukin-35 from said stem cells over the period of 72 hours.

[0284] Aspect 276: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 100% production of interleukin-37 from said stem cells over the period of 72 hours.

[0285] Aspect 277: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 25% production of interleukin-37 from said stem cells over the period of 72 hours.

[0286] Aspect 278: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 50% production of interleukin-37 from said stem cells over the period of 72 hours.

[0287] Aspect 279: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 100% production of interleukin-37 from said stem cells over the period of 72 hours.

[0288] Aspect 280: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 25% production of interleukin-38 from said stem cells over the period of 72 hours.

[0289] Aspect 281 : The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 50% production of interleukin-38 from said stem cells over the period of 72 hours.

[0290] Aspect 282: The method of Aspect 54, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 100% production of interleukin-38 from said stem cells over the period of 72 hours.

[0291] Aspect 283 : The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 25% production of FGF-1 from said stem cells over the period of 72 hours.

[0292] Aspect 284: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 50% production of FGF-1 from said stem cells over the period of 72 hours.

[0293] Aspect 285: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 100% production of FGF-1 from said stem cells over the period of 72 hours.

[0294] Aspect 286: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 25% production of FGF-2 from said stem cells over the period of 72 hours.

[0295] Aspect 287: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 50% production of FGF-2 from said stem cells over the period of 72 hours.

[0296] Aspect 288: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 100% production of FGF-2 from said stem cells over the period of 72 hours.

[0297] Aspect 289: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 25% production of Klotho from said stem cells over the period of 72 hours.

[0298] Aspect 290: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 50% production of Klotho from said stem cells over the period of 72 hours.

[0299] Aspect 291 : The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 100% production of Klotho from said stem cells over the period of 72 hours.

[0300] Aspect 292: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 25% production of HGF from said stem cells over the period of 72 hours.

[0301] Aspect 293 : The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 50% production of HGF from said stem cells over the period of 72 hours.

[0302] Aspect 294: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 100% production of HGF from said stem cells over the period of 72 hours.

[0303] Aspect 295: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 25% production of BDNF from said stem cells over the period of 72 hours.

[0304] Aspect 296: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 50% production of BDNF from said stem cells over the period of 72 hours.

[0305] Aspect 297: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 100% production of BDNF from said stem cells over the period of 72 hours.

[0306] Aspect 298: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 25% production of GM-CSF from said stem cells over the period of 72 hours.

[0307] Aspect 299: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 50% production of GM-CSF from said stem cells over the period of 72 hours.

[0308] Aspect 300: The method of Aspect 254, wherein said near infrared irradiation is administered for a sufficient time period and at a sufficient frequency to induce more that 100% production of GM-CSF from said stem cells over the period of 72 hours.

[0309] Aspect 301 : The method of Aspect 251, wherein said regenerative adjuvant is treatment is a cytokine.

[0310] Aspect 302: The method of Aspect 301, wherein said cytokine is administered together with near infrared radiation exposure.

[0311] Aspect 303: The method of Aspect 301, wherein said cytokine acts as a mitogen for said stem cells.

[0312] Aspect 304: The method of Aspect 301, wherein said cytokine acts as a self renewal factor for said stem cells.

[0313] Aspect 305: The method of Aspect 301, wherein said cytokine acts as an antiinflammatory factor for said stem cells.

[0314] Aspect 306: The method of Aspect 301, wherein said cytokine acts as an anti- apoptotic factor for said stem cells.

[0315] Aspect 307: The method of Aspect 301, wherein said cytokine acts as a dedifferentiation factor for said stem cells.

[0316] Aspect 308: The method of Aspect 301, wherein said cytokine acts as a differentiation factor for said stem cells.

[0317] Aspect 309: The method of Aspect 301, wherein said cytokine is interleukin-1 beta.

[0318] Aspect 310: The method of Aspect 309, wherein said interleukin-1 beta is administered to said stem cells at a concentration sufficient to increase expression of c- met on said stem cells by more than 25%.

[0319] Aspect 311 : The method of Aspect 309, wherein said interleukin-1 beta is administered to said stem cells at a concentration sufficient to increase expression of c- met on said stem cells by more than 50%.

[0320] Aspect 312: The method of Aspect 309, wherein said interleukin-1 beta is administered to said stem cells at a concentration sufficient to increase expression of c- met on said stem cells by more than 100%.

[0321] Aspect 313: The method of Aspect 309, wherein said interleukin-1 beta is administered to said stem cells at a concentration sufficient to increase expression of HLA-G on said stem cells by more than 25%.

[0322] Aspect 314: The method of Aspect 309, wherein said interleukin-1 beta is administered to said stem cells at a concentration sufficient to increase expression of HLA-G on said stem cells by more than 50%.

[0323] Aspect 315: The method of Aspect 309, wherein said interleukin-1 beta is administered to said stem cells at a concentration sufficient to increase expression of HLA-G on said stem cells by more than 100%.

[0324] Aspect 316: The method of Aspect 309, wherein said interleukin-1 beta is administered to said stem cells at a concentration sufficient to increase expression of LIF- 1 receptor on said stem cells by more than 25%.

[0325] Aspect 317:The method of Aspect 309, wherein said interleukin-1 beta is administered to said stem cells at a concentration sufficient to increase expression of LIF- 1 receptor on said stem cells by more than 50%.

[0326] Aspect 318: The method of Aspect 309, wherein said interleukin-1 beta is administered to said stem cells at a concentration sufficient to increase expression of LIF- 1 receptor on said stem cells by more than 100%.

[0327] Aspect 319: The method of Aspect 309, wherein said interleukin-1 beta is administered to said stem cells at a concentration sufficient to increase expression of TNF-alpha receptor on said stem cells by more than 25%.

[0328] Aspect 320: The method of Aspect 309, wherein said interleukin-1 beta is administered to said stem cells at a concentration sufficient to increase expression of TNF-alpha receptor on said stem cells by more than 50%.

[0329] Aspect 321 : The method of claim Aspect 309, wherein said interleukin-1 beta is administered to said stem cells at a concentration sufficient to increase expression of TNF-alpha receptor on said stem cells by more than 100%.

[0330] Aspect 322: The method of Aspect 301, wherein said cytokine is interleukin-4.

[0331] Aspect 323: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of soluble HLA-G by said stem cells by more than 25%.

[0332] Aspect 324: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of soluble HLA-G by said stem cells by more than 50%.

[0333] Aspect 325: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of soluble HLA-G by said stem cells by more than 100%.

[0334] Aspect 326: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of soluble TNF-alpha receptor p55 by said stem cells by more than 25%.

[0335] Aspect 327: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of soluble TNF-alpha receptor p55 by said stem cells by more than 50%.

[0336] Aspect 328: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of soluble TNF-alpha receptor p55 by said stem cells by more than 100%.

[0337] Aspect 329: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of soluble TNF-alpha receptor p75 by said stem cells by more than 25%.

[0338] Aspect 330: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of soluble TNF-alpha receptor p75 by said stem cells by more than 50%.

[0339] Aspect 331 : The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of soluble TNF-alpha receptor p75 by said stem cells by more than 100%.

[0340] Aspect 332: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of G-CSF by said stem cells by more than 25%.

[0341] Aspect 333: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of G-CSF by said stem cells by more than 50%.

[0342] Aspect 334: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of G-CSF by said stem cells by more than 100%.

[0343] Aspect 335: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of M-CSF by said stem cells by more than 25%.

[0344] Aspect 336: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of M-CSF by said stem cells by more than 50%.

[0345] Aspect 337: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of M-CSF by said stem cells by more than 100%.

[0346] Aspect 338: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of GM-CSF by said stem cells by more than 25%.

[0347] Aspect 339: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of GM-CSF by said stem cells by more than 50%.

[0348] Aspect 340: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of GM-CSF by said stem cells by more than 100%.

[0349] Aspect 341 : The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of angiopoietin by said stem cells by more than 25%.

[0350] Aspect 342: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of angiopoietin by said stem cells by more than 50%.

[0351] Aspect 343: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of angiopoietin by said stem cells by more than 100%.

[0352] Aspect 344: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of osteopontin by said stem cells by more than 25%.

[0353] Aspect 345: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of osteopontin by said stem cells by more than 50%.

[0354] Aspect 346: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of osteopontin by said stem cells by more than 60%.

[0355] Aspect 347: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of osteopontin by said stem cells by more than 70%.

[0356] Aspect 348: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of osteopontin by said stem cells by more than 80%.

[0357] Aspect 349: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of osteopontin by said stem cells by more than 90%.

[0358] Aspect 350: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of osteopontin by said stem cells by more than 100%.

[0359] Aspect 351 : The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of vastatin by said stem cells by more than 25%.

[0360] Aspect 352: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of vastatin by said stem cells by more than 50%.

[0361] Aspect 353: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of vastatin by said stem cells by more than 100%.

[0362] Aspect 354: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of EGF by said stem cells by more than 25%.

[0363] Aspect 355: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of EGF by said stem cells by more than 50%.

[0364] Aspect 356: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of EGF by said stem cells by more than 100%.

[0365] Aspect 357: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of IGF by said stem cells by more than 25%.

[0366] Aspect 358: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of IGF by said stem cells by more than 50%.

[0367] Aspect 359: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of IGF by said stem cells by more than 100%.

[0368] Aspect 360: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of IGF -BP by said stem cells by more than 25%.

[0369] Aspect 361 : The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of IGF -BP by said stem cells by more than 50%.

[0370] Aspect 362: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of IGF -BP by said stem cells by more than 50%.

[0371] Aspect 363: The method of Aspect 332, wherein said interleukin-4 as administered to said stem cells in increase production of GDF-11 by said stem cells by more than 25%.

[0372] Aspect 364: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of GDF-11 by said stem cells by more than 50%.

[0373] Aspect 365: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of GDF-11 by said stem cells by more than 100%.

[0374] Aspect 366: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of GDF-15 by said stem cells by more than 25%.

[0375] Aspect 367: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of GDF-15 by said stem cells by more than 50%.

[0376] Aspect 368: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of GDF-15 by said stem cells by more than 100%.

[0377] Aspect 369: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of endoglin by said stem cells by more than 25%.

[0378] Aspect 370: The method of Aspect 332, wherein said interleukin-4 as administered to said stem cells in increase production of endoglin by said stem cells by more than 50%.

[0379] Aspect 371 : The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of TGF-beta by said stem cells by more than 25%.

[0380] Aspect 372: The method of Aspect 322, wherein said interleukin-4 as administered to said stem cells in increase production of TGF-beta by said stem cells by more than 50%.

[0381] Aspect 373: The method of Aspect 22, wherein said interleukin-4 as administered to said stem cells in increase production of TGF-beta by said stem cells by more than 100%.

[0382] Aspect 374: The method of Aspect 322, wherein said interleukin-4 is administered to said stem cells in increase production of interleukin- 10 by said stem cells by more than 25%.

[0383] Aspect 375: The method of Aspect 322, wherein said interleukin-4 is administered to said stem cells in increase production of interleukin- 10 by said stem cells by more than 50%.

[0384] Aspect 376: The method of Aspect 322, wherein said interleukin-4 is administered to said stem cells in increase production of interleukin- 10 by said stem cells by more than 100%.

[0385] Aspect 377: The method of Aspect 322, wherein said interleukin-4 is administered to said stem cells in increase production of interleukin- 11 by said stem cells by more than 25%.

[0386] Aspect 378: The method of Aspect 322, wherein said interleukin-4 is administered to said stem cells in increase production of interleukin- 11 by said stem cells by more than 50%.

[0387] Aspect 379: The method of Aspect 322, wherein said interleukin-4 is administered to said stem cells in increase production of interleukin- 11 by said stem cells by more than 100%.

[0388] Aspect 380: The method of Aspect 322, wherein said interleukin-4 is administered to said stem cells in increase production of interleukin- 13 by said stem cells by more than 25%.

[0389] Aspect 381 : The method of Aspect 322, wherein said interleukin-4 is administered to said stem cells in increase production of interleukin- 13 by said stem cells by more than 50%.

[0390] Aspect 382: The method of Aspect 322, wherein said interleukin-4 is administered to said stem cells in increase production of interleukin- 13 by said stem cells by more than 100%.

[0391] Aspect 383: The method of Aspect 322, wherein said interleukin-4 is administered to said stem cells in increase production of interleukin- 15 by said stem cells by more than 25%.

[0392] Aspect 384: The method of Aspect 322, wherein said interleukin-4 is administered to said stem cells in increase production of interleukin- 15 by said stem cells by more than 50%.

[0393] Aspect 385: The method of Aspect 322, wherein said interleukin-4 is administered to said stem cells in increase production of interleukin- 15 by said stem cells by more than 100%.

[0394] Aspect 386: The method of Aspect 322, wherein said interleukin-4 is administered to said stem cells in increase production of interleukin-20 by said stem cells by more than 25%.

[0395] Aspect 387: The method of Aspect 322, wherein said interleukin-4 is administered to said stem cells in increase production of interleukin-20 by said stem cells by more than 50%.

[0396] Aspect 388: The method of Aspect 322, wherein said interleukin-4 is administered to said stem cells in increase production of interleukin-20 by said stem cells by more than 100%.

[0397] Aspect 390: The method of Aspect 322, wherein said interleukin-35 is administered to said stem cells in increase production of interleukin-20 by said stem cells by more than 50%.

[0398] Aspect 392: The method of Aspect 322, wherein said interleukin-4 is administered to said stem cells in increase production of interleukin-35 by said stem cells by more than 25%.

[0399] Aspect 393: The method of Aspect 322, wherein said interleukin-4 is administered to said stem cells in increase production of interleukin-35 by said stem cells by more than 50%.

[0400] Aspect 394: The method of Aspect 322, wherein said interleukin-4 is administered to said stem cells in increase production of interleukin-35 by said stem cells by more than 100%.

[0401] Aspect 395: The method of Aspect 322, wherein said interleukin-4 is administered to said stem cells in increase production of gelatinase by said stem cells by more than 25%.

[0402] Aspect 396: The method of Aspect 322, wherein said interleukin-4 is administered to said stem cells in increase production of gelatinase by said stem cells by more than 50%.

[0403] Aspect 397: The method of Aspect 322, wherein said interleukin-4 is administered to said stem cells in increase production of gelatinase by said stem cells by more than 100%.

[0404] Aspect 398: The method of Aspect 322, wherein said interleukin-4 is administered to said stem cells in increase production of collagenase by said stem cells by more than 25%.

[0405] Aspect 399: The method of Aspect 322, wherein said interleukin-4 is administered to said stem cells in increase production of collagenase by said stem cells by more than 50%.

[0406] Aspect 400: The method of Aspect 322, wherein said interleukin-4 is administered to said stem cells in increase production of collagenase by said stem cells by more than 100%.

[0407] Aspect 401 : The method of Aspect 301, wherein said cytokine is interleukin- 10.

[0408] Aspect 402: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase expression of CD34 by 25%.

[0409] Aspect 403: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase expression of CD34 by 50%.

[0410] Aspect 404: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase expression of CD34 by 100%.

[0411] Aspect 405: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase expression of c-kit by 25%.

[0412] Aspect 406: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase expression of c-kit by 50%.

[0413] Aspect 407: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase expression of c-kit by 100%.

[0414] Aspect 408: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase expression of IL- 10 receptor by 25%.

[0415] Aspect 409: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase expression of IL- 10 receptor by 50%.

[0416] Aspect 410: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase expression of IL- 10 receptor by 50%.

[0417] Aspect 411 : The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase expression of IL-35 receptor by 25%.

[0418] Aspect 412: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase expression of IL-35 receptor by 50%.

[0419] Aspect 413: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase expression of IL-35 receptor by 100%.

[0420] Aspect 414: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of TGF- beta by 25%.

[0421] Aspect 415: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of TGF- beta by 50%.

[0422] Aspect 416: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of TGF- beta by 100%.

[0423] Aspect 417: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of endoglin by 50%.

[0424] Aspect 418: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of angiopoietin by 25%.

[0425] Aspect 419: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of angiopoietin by 50%.

[0426] Aspect 420: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of angiopoietin by 100%.

[0427] Aspect 421 : The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of IGF by 25%.

[0428] Aspect 422: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of IGF by 50%.

[0429] Aspect 423: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of IGF by 100%.

[0430] Aspect 424: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of EGF by 25%.

[0431] Aspect 425: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of EGF by 50%.

[0432] Aspect 426: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of EGF by 100%.

[0433] Aspect 427: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of interleukin-20 by 25%.

[0434] Aspect 428: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of interleukin-20 by 50%.

[0435] Aspect 430: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of interleukin-22 by 25%.

[0436] Aspect 431 : The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of interleukin-22 by 50%.

[0437] Aspect 432: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of interleukin-22 by 100%.

[0438] Aspect 433: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of interleukin-35 by 25%.

[0439] Aspect 435: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of interleukin-35 by 100%.

[0440] Aspect 436: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of SMAD2 by 25%.

[0441] Aspect 437: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of SMAD2 by 50%.

[0442] Aspect 438: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of SMAD2 by 100%.

[0443] Aspect 439: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of SMALM by 25%.

[0444] Aspect 440: The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of SMALM by 50%.

[0445] Aspect 441 : The method of Aspect 401, wherein said interleukin- 10 is administered at a concentration and duration sufficient to increase production of SMALM by 100%.

[0446] Aspect 442: The method of Aspect 187, wherein said lung cancer stem cell line is generated by fusing a pluripotent stem cell with one or more cancer cell lines.

[0447] Aspect 443: The method of Aspect 442, wherein said pluripotent stem cell is a parthenogenesis-derived stem cell.

[0448] Aspect 444: The method of Aspect 442, wherein said pluripotent stem cell is an induced pluripotent stem cell.

[0449] Aspect 445: The method of Aspect 442, wherein said pluripotent stem cell is somatic cell nuclear transfer derived stem cell.

[0450] Aspect 446: The method of Aspect 442, wherein said lung cancer stem cell line expresses CD 133.

[0451] Aspect 447: The method of Aspect 442, wherein said lung cancer stem cell line expresses CXCR4.

[0452] Aspect 448: The method of Aspect 442, wherein said lung cancer stem cell line expresses aldehyde dehydrogenase.

[0453] Aspect 449: The method of Aspect 442, wherein said lung cancer stem cell line expresses CD34.

[0454] Aspect 450: The method of Aspect 442, wherein said lung cancer stem cell line expresses CD 105.

[0455] Aspect 451 : The method of Aspect 442, wherein said lung cancer stem cell line expresses CD73.

[0456] Aspect 452: The method of Aspect 442, wherein said lung cancer stem cell line expresses CD31.

[0457] Aspect 453: The method of Aspect 442, wherein said lung cancer stem cell line expresses c-met.

[0458] Aspect 454: The method of Aspect 442, wherein said lung cancer stem cell line expresses IL-6 receptor.

[0459] Aspect 455: The method of Aspect 442, wherein said lung cancer stem cell line expresses PIM3.

[0460] Aspect 456: The method of Aspect 180, wherein said lung cancer antigen source is lysate of lung cancer cells.

[0461] Aspect 457: The method of Aspect 180, wherein said lung cancer antigen source is heat shock protein bound peptides from said lung cancer cells.

[0462] Aspect 458: The method of Aspect 467, wherein said heat shock protein is hsp90.

[0463] Aspect 459: The method of Aspect 467, wherein said heat shock protein is hsp27.

[0464] Aspect 460: The method of Aspect 467, wherein said heat shock protein is hsp70.

[0465] Aspect 461 : The method of Aspect 467, wherein said heat shock protein is DNAJ.

[0466] Aspect 462: The method of Aspect 467, wherein said heat shock protein is HSPA9.

[0467] Aspect 463 : The method of Aspect 467, wherein said heat shock protein is TRAP! .

[0468] Aspect 464: The method of Aspect 467, wherein said heat shock protein is HSPA4.

[0469] Aspect 465: The method of Aspect 467, wherein said heat shock protein is GROES.

[0470] Aspect 466: The method of Aspect 467, wherein said heat shock protein is HSP47.

[0471] Aspect 467: The method of Aspect 467, wherein said heat shock protein is HSPH1.

[0472] Aspect 468: The method of Aspect 467, wherein said heat shock protein is CRYAB.

[0473] Aspect 469: The method of Aspect 467, wherein said heat shock protein is HSPB3.

[0474] Aspect 470: The method of Aspect 467, wherein said heat shock protein is CRYAA.

[0475] Aspect 471 : The method of Aspect 467, wherein said heat shock protein is HSF1.

[0476] Aspect 472: The method of Aspect 467, wherein said heat shock protein is DNAJA1.

[0477] Aspect 473 : The method of Aspect 467, wherein said heat shock protein is HSP40.

[0478] Aspect 474: The method of Aspect 457, wherein said lung cancer cell is treated with one or more agents capable of increasing expression of tumor associated antigens prior to lysis.

[0479] Aspect 475: The method of Aspect 474, wherein said tumor associated antigen is MAGE.

[0480] Aspect 476: The method of Aspect 474, wherein said tumor associated antigen is BAGE.

[0481] Aspect 477: The method of Aspect c474, wherein said tumor associated antigen is GAGE.

[0482] Aspect 478: The method of Aspect 474, wherein said tumor associated antigen is BORIS.

[0483] Aspect 479: The method of Aspect 474, wherein said tumor associated antigen is RAS.

[0484] Aspect 481 : The method of Aspect 474, wherein said tumor associated antigen is MUCl.

[0485] Aspect 482: The method of Aspect 474, wherein said tumor associated antigen is NYESO-1.

[0486] Aspect 483 : The method of Aspect 474, wherein said tumor associated antigen is CAGE.

[0487] Aspect 484: The method of Aspect 474, wherein said tumor associated antigen is Annexin- 1.

[0488] Aspect 485: The method of Aspect 474, wherein said tumor associated antigen is Annexin-5.

[0489] Aspect 486: The method of Aspect 474, wherein said tumor associated antigen is alpha V beta 3 integrin.

[0490] Aspect 487: The method of Aspect 474, wherein said tumor associated antigen is 14-2-2 theta.

[0491] Aspect 488: The method of Aspect 474, wherein said tumor associated antigen is LAMR-1.

[0492] Aspect 489: The method of Aspect 474, wherein said tumor associated antigen is alpha enolase.

[0493] Aspect 490: The method of Aspect 474, wherein said tumor associated antigen is CEA.

[0494] Aspect 491 : The method of Aspect 474, wherein said tumor associated antigen is c-myc.

[0495] Aspect 492: The method of Aspect 474, wherein said tumor associated antigen is alpha enolase.

[0496] Aspect 493 : The method of Aspect 474, wherein said tumor associated antigen is SOX1.

[0497] Aspect 494: The method of Aspect 474, wherein said tumor associated antigen is SOX2.

[0498] Aspect 495: The method of Aspect 474, wherein said tumor associated antigen is SOX3.

[0499] Aspect 496: The method of Aspect 474, wherein said tumor associated antigen is SOX21.

[0500] Aspect 497: The method of claim 474, wherein said tumor associated antigen is FGF2 receptor.

[0501] Aspect 498: The method of Aspect 474, wherein said tumor associated antigen is FGF5 receptor.

[0502] Aspect 499: The method of Aspect 474, wherein said tumor associated antigen is cytokeratin 19.

[0503] Aspect 500: The method of Aspect 474, wherein said tumor associated antigen is CECAM.

[0504] Aspect 501 : The method of Aspect 180, wherein said tumor antigens are extracted from tumor exosomes.

[0505] Aspect 502: The method of Aspect 501, wherein said tumor antigens are extracted from cancer selected from a group comprising of: acinar carcinoma, acinous carcinoma, adenocystic carcinoma, adenoid cystic carcinoma, carcinoma adenomatosum, carcinoma of adrenal cortex, alveolar carcinoma, alveolar cell carcinoma, basal cell carcinoma, carcinoma basocellulare, basaloid carcinoma, basosquamous cell carcinoma, bronchioalveolar carcinoma, bronchiolar carcinoma, bronchogenic carcinoma, cerebriform carcinoma, cholangiocellular carcinoma, chorionic carcinoma, colloid carcinoma, comedo carcinoma, corpus carcinoma, cribriform carcinoma, carcinoma en cuirasse, carcinoma cutaneum, cylindrical carcinoma, cylindrical cell carcinoma, duct carcinoma, carcinoma durum, embryonal carcinoma, encephaloid carcinoma, epiennoid carcinoma, carcinoma epitheliale adenoides, exophytic carcinoma, carcinoma ex ulcere, carcinoma fibrosum, gelatiniform carcinoma, gelatinous carcinoma, giant cell carcinoma, signet-ring cell carcinoma, carcinoma simplex, small-cell carcinoma, solanoid carcinoma, spheroidal cell carcinoma, spindle cell carcinoma, carcinoma spongiosum, squamous carcinoma, squamous cell carcinoma, string carcinoma, carcinoma telangiectaticum, carcinoma telangiectodes, transitional cell carcinoma, carcinoma tuberosum, tuberous carcinoma, verrmcous carcinoma, carcinoma villosum, carcinoma gigantocellulare, glandular carcinoma, granulosa cell carcinoma, hair-matrix carcinoma, hematoid carcinoma, hepatocellular carcinoma, Hurthle cell carcinoma, hyaline carcinoma, hypemephroid carcinoma, infantile embryonal carcinoma, carcinoma in situ, intraepidermal carcinoma, intraepithelial carcinoma, Krompecher's carcinoma,Kulchitzky-cell carcinoma, large-cell carcinoma, lenticular carcinoma, carcinoma lenticulare, lipomatous carcinoma, lymphoepithelial carcinoma, carcinoma medullare, medullary carcinoma, melanotic carcinoma, carcinoma molle, mucinous carcinoma, carcinoma muciparum, carcinoma mucocellulare, mucoepidermoid carcinoma, carcinoma mucosum, mucous carcinoma, carcinoma myxomatodes, naspharyngeal carcinoma, oat cell carcinoma, carcinoma ossificans, osteoid carcinoma, papillary carcinoma, periportal carcinoma, preinvasive carcinoma, prickle cell carcinoma, pultaceous carcinoma, renal cell carcinoma of kidney, reserve cell carcinoma, carcinoma sarcomatodes, Schneiderian carcinoma, scirrhous carcinoma, and carcinoma scroti, The term "sarcoma" generally refers to a tumor which is made up of a substance like the embryonic connective tissue and is generally composed of closely packed cells embedded in a fibrillar, heterogeneous, or homogeneous substance. Sarcomas include, chondrosarcoma, fibrosarcoma, lymphosarcoma, melanosarcoma, myxosarcoma, osteosarcoma, endometrial sarcoma, stromal sarcoma, Ewing's sarcoma, fascial sarcoma, fibroblastic sarcoma, giant cell sarcoma, Abernethy's sarcoma, adipose sarcoma, liposarcoma, alveolar soft part sarcoma, ameloblastic sarcoma, botryoid sarcoma, chloroma sarcoma, chorio carcinoma, embryonal sarcoma, Wilns' tumor sarcoma, granulocytic sarcoma, Hodgkin's sarcoma, idiopathic multiple pigmented hemorrhagic sarcoma, immunoblastic sarcoma of B cells, lymphoma, immunoblastic sarcoma of T-cells, Jensen's sarcoma, Kaposi's sarcoma, Kupffer cell sarcoma, angiosarcoma, leukosarcoma, malignant mesenchymoma sarcoma, parosteal sarcoma, reticulocytic sarcoma, Rous sarcoma, serocystic sarcoma, synovial sarcoma, and telangiectaltic sarcoma. Additional exemplary neoplasias include, for example, Hodgkin's Disease, Non-Hodgkin's Lymphoma, multiple myeloma, neuroblastoma, breast cancer, ovarian cancer, lung cancer, rhabdomyosarcoma, primary thrombocytosis, primary macroglobulinemia, small-cell lung tumors, primary brain tumors, stomach cancer, colon cancer, malignant pancreatic insulanoma, malignant carcinoid, premalignant skin lesions, testicular cancer, lymphomas, thyroid cancer, neuroblastoma, esophageal cancer, genitourinary tract cancer, malignant hypercalcemia, cervical cancer, endometrial cancer, and adrenal cortical cancer.

[0506] Aspect 503. The method of Aspect 474, wherein said agents that increase expression of said tumor associated antigens are cytokines.

[0507] Aspect 504: The method of Aspect 474, wherein said agents that increase expression of said tumor associated antigens is hyperthermia.

[0508] Aspect 505: The method of Aspect 474, wherein said agents that increase expression of said tumor associated antigens are histone deacetylase inhibitors.

[0509] Aspect 506: The method of Aspect 505, wherein said histone deacetylase inhibitor is sulforaphane.

[0510] Aspect 507: The method of Aspect 505, wherein said histone deacetylase inhibitor is trichostatin A.

[0511] Aspect 508: The method of Aspect 505, wherein said histone deacetylase inhibitor is phenylbutyrate

[0512] Aspect 509: The method of Aspect 505, wherein said histone deacetylase inhibitor is butyrate.

[0513] Aspect 510: The method of Aspect 505, wherein said histone deacetylase inhibitor is valproic acid.

[0514] Aspect 511 : The method of Aspect 505, wherein said histone deacetylase inhibitor is thymoquinone.

[0515] Aspect 512: The method of Aspect 180, wherein prior to or subsequent to immunization with senescent derived antigen said patient is boosted with administration of proteins or peptides derived from tumor associated antigens.

[0516] Aspect 513: The method of Aspect 512, wherein said tumor associated antigens are administered together with one or more adjuvants.

[0517] Aspect 514: The method of Aspect 513, wherein said adjuvant is an agonistic anti CD40 antibody.

[0518] Aspect 515: The method of Aspect 513, wherein said adjuvant is an agonistic anti CD40 ligand antibody.

[0519] Aspect 516: The method of Aspect 513, wherein said adjuvant is an agonistic anti CD3 antibody.

[0520] Aspect 517: The method of Aspect 513, wherein said adjuvant is an agonistic anti CD28 antibody.

[0521] Aspect 518: The method of Aspect 513, wherein said adjuvant is an agonistic anti 4.1 BB antibody.

[0522] Aspect 519: The method of Aspect 513, wherein said adjuvant is an agonistic anti CD25 antibody.

[0523] Aspect 520: The method of Aspect 513, wherein said adjuvant is an agonistic anti IL -7 receptor antibody.

[0524] Aspect 521 : The method of Aspect 513, wherein said adjuvant is an agonistic anti IL- 12 receptor antibody.

[0525] Aspect 522: The method of Aspect 513, wherein said adjuvant is an agonistic anti IL- 15 receptor antibody.

[0526] Aspect 523: The method of Aspect 513, wherein said adjuvant is an agonistic anti IL- 17 receptor antibody.

[0527] Aspect 524: The method of Aspect 513, wherein said adjuvant is an agonistic anti IL- 18 receptor antibody.

[0528] Aspect 525: The method of Aspect 513, wherein said adjuvant is an agonistic anti IL -33 receptor antibody.

[0529] Aspect 526: The method of Aspect 513, wherein said adjuvant is an agonistic anti interferon alpha receptor antibody.

[0530] Aspect 527: The method of Aspect 513, wherein said adjuvant is an agonistic anti interferon gamma receptor antibody.

[0531] Aspect 528: The method of claim 513, wherein said adjuvant is an agonistic anti interferon tau receptor antibody.

[0532] Aspect 529: The method of Aspect 513, wherein said adjuvant is an agonistic anti-TNF alpha receptor antibody.

[0533] Aspect 530: The method of Aspect 513, wherein said adjuvant is an agonistic anti lymphotoxin receptor antibody.

[0534] Aspect 531 : The method of Aspect 513, wherein said adjuvant is an agonistic anti TRANCE receptor antibody.

[0535] Aspect 532: The method of Aspect 513, wherein said adjuvant is an agonistic anti TRAIL receptor antibody.

[0536] Aspect 533: The method of Aspect 503, wherein said antigen is conjugated to one or more molecules to increase immunogenicity.

[0537] Aspect 534: The method of Aspect 533, wherein said molecule conjugated to increase immunogenicity is a toll like receptor agonist.

[0538] Aspect 535: The method of Aspect 534, wherein said toll like receptor agonist is poly IC.

[0539] Aspect 536: The method of Aspect 534, wherein said toll like receptor agonist is beta defensin.

[0540] Aspect 537: The method of Aspect 534, wherein said toll like receptor agonist is HMGBl.

[0541] Aspect 538: The method of Aspect 534, wherein said toll like receptor agonist is fibronectin EDA.

[0542] Aspect 539: The method of Aspect 534, wherein said toll like receptor agonist is snapin.

[0543] Aspect 540: The method of Aspect 534, wherein said toll like receptor agonist is tenascin.

[0544] Aspect 541 : The method of Aspect 534, wherein said toll like receptor agonist is beta glucan.

[0545] Aspect 542: The method of Aspect 534, wherein said toll like receptor agonist is low molecular weight hyaluronic acid.

[0546] Aspect 543: The method of Aspect 534, wherein said toll like receptor agonist is an aminoalkyl glucosaminide phosphates.

[0547] Aspect 544: The method of Aspect 534, wherein said toll like receptor agonist is a lipopolysaccharide.

[0548] Aspect 545: The method of claim Aspect 534, wherein said toll like receptor agonist is an aminoalkyl glucosaminide phosphates.

[0549] Aspect 546: The method of Aspect 534, wherein said toll like receptor agonist is Pam2CSK4.

[0550] Aspect 547: The method of Aspect 534, wherein said toll like receptor agonist is Pam3CSK4.

[0551] Aspect 548: The method of Aspect 534, wherein said toll like receptor agonist is imiquimod.

[0552] Aspect 549: The method of Aspect 534, wherein said toll like receptor agonist is resmiquimod.

[0553] Aspect 550: The method of Aspect 534, wherein said toll like receptor agonist is beta glucan.

[0554] Aspect 551 : The method of Aspect 534, wherein said toll like receptor agonist is flagellin.

[0555] Aspect 552: The method of Aspect 534, wherein said toll like receptor agonist is CL075.

[0556] Aspect 553: The method of Aspect 534, wherein said toll like receptor agonist is DSR6434.

[0557] Aspect 554: The method of Aspect 534, wherein said toll like receptor agonist is zymosan.

[0558] Aspect 555: The method of Aspect 534, wherein said toll like receptor agonist is CpG DNA.

[0559] Aspect 556: The method of Aspect 534, wherein said toll like receptor agonist is Poly AU.

[0560] Aspect 557: The method of Aspect 534, wherein said toll like receptor agonist is Poly G10.

[0561] Aspect 558: The method of Aspect 534, wherein said toll like receptor agonist is Poly G3.

[0562] Aspect 559: The method of Aspect 534, wherein said toll like receptor agonist is BCG.

[0563] Aspect 560: The method of Aspect 534, wherein said toll like receptor agonist is yeast wall extract.

[0564] Aspect 561 : The method of Aspect 513, wherein said tumor associated antigen is ERG.

[0565] Aspect 562: The method of Aspect 513, wherein said tumor associated antigen is WTl.

[0566] Aspect 563 : The method of Aspect 513, wherein said tumor associated antigen is ALS.

[0567] Aspect 564: The method of Aspect 513, wherein said tumor associated antigen is BCR-ABL.

[0568] Aspect 565: The method of Aspect 513, wherein said tumor associated antigen is mutated RAS.

[0569] Aspect 566: The method of Aspect 513, wherein said tumor associated antigen is ETV6.

[0570] Aspect 567: The method of Aspect 513, wherein said tumor associated antigen is LMP2.

[0571] Aspect 568: The method of Aspect 513, wherein said tumor associated antigen is p53.

[0572] Aspect 569: The method of Aspect 513, wherein said tumor associated antigen is MYC-N.

[0573] Aspect 570: The method of Aspect 513, wherein said tumor associated antigen is survivin.

[0574] Aspect 571 : The method of Aspect 513, wherein said tumor associated antigen is androgen receptor.

[0575] Aspect 572: The method of Aspect 513, wherein said tumor associated antigen is RhoC.

[0576] Aspect 573: The method of Aspect 513, wherein said tumor associated antigen is cyclin Bl.

[0577] Aspect 574: The method of Aspect 513, wherein said tumor associated antigen is EGFRvIII.

[0578] Aspect 575: The method of Aspect 513, wherein said tumor associated antigen is EphA2.

[0579] Aspect 576: The method of Aspect 513, wherein said tumor associated antigen is B cell idiotype.

[0580] Aspect 577: The method of Aspect 513, wherein said tumor associated antigen is T cell idiotype.

[0581] Aspect 578: The method of Aspect 513, wherein said tumor associated antigen is ML- 1 AB.

[0582] Aspect 579: The method of Aspect 513, wherein said tumor associated antigen is BORIS.

[0583] Aspect 580: The method of Aspect 513, wherein said tumor associated antigen is ETV6.

[0584] Aspect 581 : The method of Aspect 513, wherein said tumor associated antigen is hTERT.

[0585] Aspect 582: The method of Aspect 513, wherein said tumor associated antigen is PLACE

[0586] Aspect 583 : The method of Aspect 513, wherein said tumor associated antigen is HPV E6.

[0587] Aspect 584: The method of Aspect 513, wherein said tumor associated antigen is HPV E7.

[0588] Aspect 585: The method of Aspect 513, wherein said tumor associated antigen is OY-TESl.

[0589] Aspect 586: The method of Aspect 513, wherein said tumor associated antigen is Her2 / neu.

[0590] Aspect 587: The method of Aspect 513, wherein said tumor associated antigen is Pax3.

[0591] Aspect 588: The method of Aspect 513, wherein said tumor associated antigen is NYBRl.

[0592] Aspect 589: The method of Aspect 513, wherein said tumor associated antigen is MAGE A3.

[0593] Aspect 590: The method of Aspect 513, wherein said tumor associated antigen is polysialic acid.

[0594] Aspect 591 : The method of Aspect 513, wherein said tumor associated antigen is AFP.

[0595] Aspect 592: The method of Aspect 513, wherein said tumor associated antigen is PAX5.

[0596] Aspect 593 : The method of Aspect 513, wherein said tumor associated antigen is sperm protein 17.

[0597] Aspect 594: The method of Aspect 513, wherein said tumor associated antigen is GD3.

[0598] Aspect 595: The method of Aspect 513, wherein said tumor associated antigen is Fucosyl GM1.

[0599] Aspect 596: The method of Aspect 513, wherein said tumor associated antigen is mesothelin.

[0600] Aspect 597: The method of Aspect 513, wherein said tumor associated antigen is PSMA.

[0601] Aspect 598: The method of Aspect 513, wherein said tumor associated antigen is GD2.

[0602] Aspect 599: The method of Aspect 513, wherein said tumor associated antigen is sLE(x).

[0603] Aspect 600: The method of Aspect 513, wherein said tumor associated antigen is HMWMAA.

[0604] Aspect 601 : The method of Aspect 513, wherein said tumor associated antigen is CYPIBl.

[0605] Aspect 602: The method of Aspect 513, wherein said tumor associated antigen is sperm fibrous sheath protein.

[0606] Aspect 603 : The method of Aspect 513, wherein said tumor associated antigen is B7H3.

[0607] Aspect 604: The method of Aspect 513, wherein said tumor associated antigen is TRP2.

[0608] Aspect 605: The method of Aspect 513, wherein said tumor associated antigen is indolamine 2,3 dioxygenase.

[0609] Aspect 606: The method of Aspect 513, wherein said tumor associated antigen is AKAP4.

[0610] Aspect 607: The method of Aspect 513, wherein said tumor associated antigen is XAGE.

[0611] Aspect 608: The method of Aspect 513, wherein said tumor associated antigen is CEAl.

[0612] Aspect 609: The method of Aspect 513, wherein said tumor associated antigen is Tn.

[0613] Aspect 610: The method of Aspect 513, wherein said tumor associated antigen is GloboH.

[0614] Aspect 611 : The method of Aspect 513, wherein said tumor associated antigen is SSX2.

[0615] Aspect 612: The method of Aspect 513, wherein said tumor associated antigen is RGS5.

[0616] Aspect 613 : The method of Aspect 513, wherein said tumor associated antigen is SART3.

[0617] Aspect 614: The method of Aspect 513, wherein said tumor associated antigen is gplOO.

[0618] Aspect 615: The method of Aspect 513, wherein said tumor associated antigen is MelanA.

[0619] Aspect 616: The method of Aspect 513, wherein said tumor associated antigen is tyrosinase.

[0620] Aspect 617: The method of Aspect 513, wherein said tumor associated antigen is GM3 ganglioside.

[0621] Aspect 618: The method of Aspect 513, wherein said tumor associated antigen is proteinase 3.

[0622] Aspect 619: The method of Aspect 513, wherein said tumor associated antigen is PAGE4.

[0623] Aspect 620: The method of Aspect 513, wherein said tumor associated antigen is sTn.

[0624] Aspect 621 : The method of Aspect 513, wherein said tumor associated antigen is Carbonic Anydrase IX.

[0625] Aspect 622: The method of Aspect 513, wherein said tumor associated antigen is PSCA.

[0626] Aspect 623 : The method of Aspect 513, wherein said tumor associated antigen is Legumain.

[0627] Aspect 624: The method of Aspect 513, wherein said tumor associated antigen is protamin2.

[0628] Aspect 625: The method of Aspect 513, wherein said tumor associated antigen is PSA.

[0629] Aspect 626: The method of Aspect 513, wherein said tumor associated antigen is Tie2.

[0630] Aspect 627: The method of Aspect 513, wherein said tumor associated antigen is MAD-CT2.

[0631] Aspect 628: The method of Aspect 513, wherein said tumor associated antigen is prostatic acid phosphatase.

[0632] Aspect 629: The method of Aspect 513, wherein said tumor associated antigen is PDGFR2-beta.

[0633] Aspect 630: The method of Aspect 513, wherein said tumor associated antigen is NA17.

[0634] Aspect 631 : The method of Aspect 513, wherein said tumor associated antigen is VEGFR2.

[0635] Aspect 632: The method of Aspect 513, wherein said tumor associated antigen is FAP.

[0636] Aspect 633 : The method of Aspect 513, wherein said tumor associated antigen is Lek.

[0637] Aspect 634: The method of Aspect 513, wherein said tumor associated antigen is OCT4.

[0638] Aspect 635: The method of Aspect 513, wherein said tumor associated antigen is Sox-2.

[0639] Aspect 636: The method of Aspect 513, wherein said tumor associated antigen is Nanog.

[0640] Aspect 637: The method of Aspect 513, wherein said tumor associated antigen is KLF4.

[0641] Aspect 638: The method of Aspect 180, wherein said antigen presenting cell expresses CD80.

[0642] Aspect 639: The method of Aspect 180, wherein said antigen presenting cell expresses CD86.

[0643] Aspect 640: The method of Aspect 180, wherein said antigen presenting cell expresses CD40.

[0644] Aspect 641 : The method of Aspect 180, wherein said antigen presenting cell is a dendritic cell.

[0645] Aspect 642: The method of Aspect 641, wherein said dendritic cell is a myeloid dendritic cell.

[0646] Aspect 643: The method of Aspect 641, wherein said dendritic cell expresses CDl lc.

[0647] Aspect 644: The method of Aspect 641, wherein said dendritic cell is a myeloid dendritic cell is engineered to possess a reduced amount of one or more coinhibitory molecules as compared to a naive dendritic cell.

[0648] Aspect 645: The method of Aspect 644, wherein said coinhibitory molecule is interleukin-10.

[0649] Aspect 646: The method of Aspect 645, wherein reduction of interleukin- 10 is achieved by treatment with a short interfering RNA to interleukin- 10.

[0650] Aspect 647: The method of Aspect 645, wherein reduction of interleukin- 10 is achieved by treatment with a short hairpin RNA to interleukin- 10.

[0651] Aspect 648: The method of Aspect 645, wherein reduction of interleukin- 10 is achieved by treatment with an antisense oligonucleotide to interleukin- 10.

[0652] Aspect 649: The method of Aspect 645, wherein reduction of interleukin- 10 is achieved by treatment with a hammerhead ribozyme to interleukin- 10.

[0653] Aspect 650: The method of Aspect 645, wherein reduction of interleukin- 10 is achieved by treatment with a ribozyme to interleukin- 10.

[0654] Aspect 651 : The method of Aspect 645, wherein reduction of interleukin- 10 is achieved by treatment with a gene editing means targeting interleukin- 10.

[0655] Aspect 652: The method of Aspect 644, wherein said coinhibitory molecule is interleukin-4.

[0656] Aspect 653 : The method of Aspect 652, wherein reduction of interleukin-4 is achieved by treatment with a short interfering RNA to interleukin-4.

[0657] Aspect 654: The method of Aspect 652, wherein reduction of interleukin-4 is achieved by treatment with a short hairpin RNA to interleukin-4.

[0658] Aspect 655: The method of Aspect 652, wherein reduction of interleukin-4 is achieved by treatment with an antisense oligonucleotide to interleukin-4.

[0659] Aspect 656: The method of Aspect 652, wherein reduction of interleukin-4 is achieved by treatment with a hammerhead ribozyme to interleukin-4.

[0660] Aspect 657: The method of Aspect 652, wherein reduction of interleukin-4 is achieved by treatment with a ribozyme to interleukin-4.

[0661] Aspect 658: The method of Aspect 652, wherein reduction of interleukin-4 is achieved by treatment with a gene editing means targeting interleukin-4.

[0662] Aspect 659: The method of Aspect 644, wherein said coinhibitory molecule is interleukin-13.

[0663] Aspect 660: The method of Aspect 659, wherein reduction of interleukin- 13 is achieved by treatment with a short interfering RNA to interleukin-13.

[0664] Aspect 661 : The method of Aspect 652, wherein reduction of interleukin- 13 is achieved by treatment with a short hairpin RNA to interleukin-13.

[0665] Aspect 662: The method of Aspect 652, wherein reduction of interleukin- 13 is achieved by treatment with an antisense oligonucleotide to interleukin-13.

[0666] Aspect 663 : The method of Aspect 652, wherein reduction of interleukin- 13 is achieved by treatment with a hammerhead ribozyme to interleukin-13.

[0667] Aspect 664: The method of Aspect 652, wherein reduction of interleukin- 13 is achieved by treatment with a ribozyme to interleukin-13.

[0668] Aspect 665: The method of Aspect 652, wherein reduction of interleukin- 13 is achieved by treatment with a gene editing means targeting interleukin-13.

[0669] Aspect 667: The method of Aspect 644, wherein said coinhibitory molecule is interleukin-20.

[0670] Aspect 668: The method of Aspect 667, wherein reduction of interleukin-20 is achieved by treatment with a short interfering RNA to interleukin-20.

[0671] Aspect 669: The method of Aspect 667, wherein reduction of interleukin-20 is achieved by treatment with a short hairpin RNA to interleukin-20.

[0672] Aspect 670: The method of Aspect 667, wherein reduction of interleukin-20 is achieved by treatment with an antisense oligonucleotide to interleukin-20.

[0673] Aspect 671 : The method of Aspect 667, wherein reduction of interleukin-20 is achieved by treatment with a hammerhead ribozyme to interleukin-20.

[0674] Aspect 672: The method of Aspect 667, wherein reduction of interleukin-20 is achieved by treatment with a ribozyme to interleukin-20.

[0675] Aspect 673 : The method of Aspect 667, wherein reduction of interleukin-20 is achieved by treatment with a gene editing means targeting interleukin-20.

[0676] Aspect 674: The method of Aspect 644, wherein said coinhibitory molecule is interleukin-22.

[0677] Aspect 675: The method of Aspect 674, wherein reduction of interleukin-22 is achieved by treatment with a short interfering RNA to interleukin-22.

[0678] Aspect 676: The method of Aspect 674, wherein reduction of interleukin-22 is achieved by treatment with a short hairpin RNA to interleukin-22.

[0679] Aspect 677: The method of Aspect 674, wherein reduction of interleukin-22 is achieved by treatment with an antisense oligonucleotide to interleukin-22.

[0680] Aspect 678: The method of Aspect 674, wherein reduction of interleukin-22 is achieved by treatment with a hammerhead ribozyme to interleukin-22.

[0681] Aspect 679: The method of Aspect 674, wherein reduction of interleukin-22 is achieved by treatment with a ribozyme to interleukin-22.

[0682] Aspect 680: The method of Aspect 674, wherein reduction of interleukin-22 is achieved by treatment with a gene editing means targeting interleukin-22.

[0683] Aspect 681 : The method of Aspect 644, wherein said coinhibitory molecule is interleukin-35.

[0684] Aspect 682: The method of Aspect 681, wherein reduction of interleukin-35 is achieved by treatment with a short interfering RNA to interleukin-35.

[0685] Aspect 683 : The method of Aspect 682, wherein reduction of interleukin-35 is achieved by treatment with a short hairpin RNA to interleukin-35.

[0686] Aspect 684: The method of Aspect 682, wherein reduction of interleukin-35 is achieved by treatment with an antisense oligonucleotide to interleukin-35.

[0687] Aspect 685: The method of Aspect 682, wherein reduction of interleukin-35 is achieved by treatment with a hammerhead ribozyme to interleukin-35.

[0688] Aspect 686: The method of Aspect 682, wherein reduction of interleukin-35 is achieved by treatment with a ribozyme to interleukin-35.

[0689] Aspect 687: The method of Aspect 682, wherein reduction of interleukin-35 is achieved by treatment with a gene editing means targeting interleukin-35.

[0690] Aspect 688: The method of Aspect 644, wherein said coinhibitory molecule is interleukin-37.

[0691] Aspect 689: The method of Aspect 688, wherein reduction of interleukin-37 is achieved by treatment with a short interfering RNA to interleukin-37.

[0692] Aspect 690: The method of Aspect 688, wherein reduction of interleukin-37 is achieved by treatment with a short hairpin RNA to interleukin-37.

[0693] Aspect 691 : The method of Aspect 688, wherein reduction of interleukin-37 is achieved by treatment with an antisense oligonucleotide to interleukin-37.

[0694] Aspect 692: The method of Aspect 688, wherein reduction of interleukin-37 is achieved by treatment with a hammerhead ribozyme to interleukin-37.

[0695] Aspect 693 : The method of Aspect 688, wherein reduction of interleukin-35 is achieved by treatment with a ribozyme to interleukin-37.

[0696] Aspect 694: The method of Aspect 688, wherein reduction of interleukin-37 is achieved by treatment with a gene editing means targeting interleukin-37.

[0697] Aspect 695: The method of Aspect 644, wherein said coinhibitory molecule is interleukin-38.

[0698] Aspect 696: The method of Aspect 695, wherein reduction of interleukin-38 is achieved by treatment with a short interfering RNA to interleukin-38.

[0699] Aspect 697: The method of Aspect 695, wherein reduction of interleukin-38 is achieved by treatment with a short hairpin RNA to interleukin-37.

[0700] Aspect 698: The method of Aspect 695, wherein reduction of interleukin-38 is achieved by treatment with an antisense oligonucleotide to interleukin-38.

[0701] Aspect 699: The method of Aspect 695, wherein reduction of interleukin-38 is achieved by treatment with a hammerhead ribozyme to interleukin-38.

[0702] Aspect 700: The method of Aspect 695, wherein reduction of interleukin-38 is achieved by treatment with a ribozyme to interleukin-38.

[0703] Aspect 701 : The method of Aspect 695, wherein reduction of interleukin-38 is achieved by treatment with a gene editing means targeting interleukin-38.

[0704] Aspect 702: The method of Aspect 644, wherein said coinhibitory molecule is TGF-beta.

[0705] Aspect 703 : The method of Aspect 702, wherein reduction of TGF-beta is achieved by treatment with a short interfering RNA to TGF-beta.

[0706] Aspect 704: The method of Aspect 702, wherein reduction of TGF-beta is achieved by treatment with a short hairpin RNA to TGF-beta.

[0707] Aspect 705: The method of Aspect 702, wherein reduction of TGF-beta is achieved by treatment with an antisense oligonucleotide to TGF-beta.

[0708] Aspect 706: The method of Aspect 702, wherein reduction of TGF-beta is achieved by treatment with a hammerhead ribozyme to TGF-beta.

[0709] Aspect 707: The method of Aspect 702, wherein reduction of TGF-beta is achieved by treatment with a ribozyme to TGF-beta.

[0710] Aspect 708: The method of Aspect 702, wherein reduction of TGF-beta is achieved by treatment with a gene editing means targeting TGF-beta.

[0711] Aspect 709: The method of Aspect 644, wherein said coinhibitory molecule is endoglin.

[0712] Aspect 710: The method of Aspect 709, wherein reduction of endoglin is achieved by treatment with a short interfering RNA to endoglin.

[0713] Aspect 711 : The method of Aspect 709, wherein reduction of endoglin is achieved by treatment with a short hairpin RNA to endoglin.

[0714] Aspect 712: The method of Aspect 709, wherein reduction of endoglin is achieved by treatment with an antisense oligonucleotide to endoglin.

[0715] Aspect 713: The method of Aspect 709, wherein reduction of endoglin is achieved by treatment with a hammerhead ribozyme to endoglin

[0716] Aspect 714: The method of Aspect 709, wherein reduction of endoglin is achieved by treatment with a ribozyme to endoglin.

[0717] Aspect 715: The method of Aspect 709, wherein reduction of endoglin is achieved by treatment with a gene editing means targeting endoglin.

[0718] Aspect 716: The method of Aspect 644, wherein said coinhibitory molecule is HLA-G.

[0719] Aspect 717: The method of Aspect 716, wherein reduction of HLA-G is achieved by treatment with a short interfering RNA to HLA-G.

[0720] Aspect 718: The method of Aspect 716, wherein reduction of HLA-G is achieved by treatment with a short hairpin RNA to HLA-G.

[0721] Aspect 719: The method of Aspect 716, wherein reduction of HLA-G is achieved by treatment with an antisense oligonucleotide to HLA-G.

[0722] Aspect 720: The method of Aspect 716, wherein reduction of HLA-G is achieved by treatment with a hammerhead ribozyme to HLA-G.

[0723] Aspect 721 : The method of Aspect 716, wherein reduction of HLA-G is achieved by treatment with a ribozyme to HLA-G.

[0724] Aspect 722: The method of Aspect 716, wherein reduction of HLA-G is achieved by treatment with a gene editing means targeting HLA-G.

[0725] Aspect 723: The method of Aspect 644, wherein said coinhibitory molecule is ILT3.

[0726] Aspect 724: The method of Aspect 723, wherein reduction of ILT3 is achieved by treatment with a short interfering RNA to ILT3.

[0727] Aspect 725: The method of Aspect 723, wherein reduction of ILT3 is achieved by treatment with a short hairpin RNA to ILT3.

[0728] Aspect 726: The method of Aspect 723, wherein reduction of ILT3 is achieved by treatment with an antisense oligonucleotide to ILT3.

[0729] Aspect 727: The method of Aspect 723, wherein reduction of ILT3 is achieved by treatment with a hammerhead ribozyme to ILT3.

[0730] Aspect 728: The method of Aspect 723, wherein reduction of ILT3 is achieved by treatment with a ribozyme to ILT3.

[0731] Aspect 729: The method of Aspect 723, wherein reduction of ILT3 is achieved by treatment with a gene editing means targeting ILT3.

[0732] Aspect 730: The method of Aspect 644, wherein said coinhibitory molecule is LIF.

[0733] Aspect 731 : The method of Aspect 730, wherein reduction of LIF is achieved by treatment with a short interfering RNA to LIF.

[0734] Aspect 732: The method of Aspect 730, wherein reduction of LIF is achieved by treatment with a short hairpin RNA to LIF.

[0735] Aspect 733. The method of Aspect 730, wherein reduction of LIF is achieved by treatment with an antisense oligonucleotide to LIF.

[0736] Aspect 734: The method of Aspect 730, wherein reduction of LIF is achieved by treatment with a hammerhead ribozyme to LIF.

[0737] Aspect 735: The method of Aspect 730, wherein reduction of LIF is achieved by treatment with a ribozyme to LIF.

[0738] Aspect 736: The method of Aspect 730, wherein reduction of LIF is achieved by treatment with a gene editing means targeting LIF.

[0739] Aspect 737: The method of Aspect 644, wherein said coinhibitory molecule is activated protein c (APC).

[0740] Aspect 738: The method of Aspect 737, wherein reduction of APC is achieved by treatment with a short interfering RNA to APC.

[0741] Aspect 739: The method of Aspect 737, wherein reduction of APC is achieved by treatment with a short hairpin RNA to APC.

[0742] Aspect 740: The method of Aspect 737, wherein reduction of APC is achieved by treatment with an antisense oligonucleotide to APC.

[0743] Aspect 741 : The method of Aspect 737, wherein reduction of APC is achieved by treatment with a hammerhead ribozyme to APC.

[0744] Aspect 742: The method of Aspect 737, wherein reduction of APC is achieved by treatment with a ribozyme to APC.

[0745] Aspect 743: The method of Aspect 737, wherein reduction of APC is achieved by treatment with a gene editing means targeting APC.

[0746] Aspect 744: The method of Aspect 644, wherein said coinhibitory molecule is absent in melanoma 2 (AIM2).

[0747] Aspect 745: The method of Aspect 744, wherein reduction of AIM2 is achieved by treatment with a short interfering RNA to AIM2.

[0748] Aspect 746: The method of Aspect 744, wherein reduction of AIM2 is achieved by treatment with a short hairpin RNA to AIM2.

[0749] Aspect 747: The method of Aspect 744, wherein reduction of AIM2 is achieved by treatment with an antisense oligonucleotide to AIM2.

[0750] Aspect 748: The method of Aspect 744, wherein reduction of AIM2 is achieved by treatment with a hammerhead ribozyme to AIM2.

[0751] Aspect 749: The method of Aspect 744, wherein reduction of AIM2 is achieved by treatment with a ribozyme to AIM2.

[0752] Aspect 750: The method of Aspect 744, wherein reduction of AIM2 is achieved by treatment with a gene editing means targeting AIM2.

[0753] Aspect 751 : The method of Aspect 644, wherein said coinhibitory molecule is CD200.

[0754] Aspect 752: The method of Aspect 751, wherein reduction of CD200 is achieved by treatment with a short interfering RNA to CD200.

[0755] Aspect 753 : The method of Aspect 751, wherein reduction of CD200 is achieved by treatment with a short hairpin RNA to CD200.

[0756] Aspect 754: The method of Aspect 751, wherein reduction of CD200 is achieved by treatment with an antisense oligonucleotide to CD200.

[0757] Aspect 755: The method of Aspect 751, wherein reduction of CD200 is achieved by treatment with a hammerhead ribozyme to CD200.

[0758] Aspect 756: The method of Aspect 751, wherein reduction of CD200 is achieved by treatment with a ribozyme to CD200.

[0759] Aspect 757: The method of Aspect 751, wherein reduction of CD200 is achieved by treatment with a gene editing means targeting CD200.

[0760] Aspect 758: The method of Aspect 644, wherein said coinhibitory molecule is FGL2.

[0761] Aspect 759: The method of Aspect 758, wherein reduction of FGL2 is achieved by treatment with a short interfering RNA to FGL2.

[0762] Aspect 760: The method of Aspect 758, wherein reduction of FGL2 is achieved by treatment with a short hairpin RNA to FGL2.

[0763] Aspect 761 : The method of Aspect 758, wherein reduction of FGL2 is achieved by treatment with an antisense oligonucleotide to FGL2.

[0764] Aspect 762: The method of Aspect 758, wherein reduction of FGL2 is achieved by treatment with a hammerhead ribozyme to FGL2.

[0765] Aspect 763: The method of Aspect 758, wherein reduction of FGL2 is achieved by treatment with a ribozyme to FGL2.

[0766] Aspect 764: The method of Aspect 758, wherein reduction of FGL2 is achieved by treatment with a gene editing means targeting FGL2.

[0767] Aspect 765: The method of Aspect 644, wherein said coinhibitory molecule isVEGF.

[0768] Aspect 766: The method of Aspect 765, wherein reduction of VEGF is achieved by treatment with a short interfering RNA to VEGF.

[0769] Aspect 767: The method of Aspect 765, wherein reduction of VEGF is achieved by treatment with a short hairpin RNA to VEGF.

[0770] Aspect 768: The method of Aspect 765, wherein reduction of VEGF is achieved by treatment with an antisense oligonucleotide to VEGF.

[0771] Aspect 769: The method of Aspect 765, wherein reduction of VEGF is achieved by treatment with a hammerhead ribozyme to VEGF.

[0772] Aspect 770: The method of Aspect 765, wherein reduction of VEGF is achieved by treatment with a ribozyme to VEGF.

[0773] Aspect 771 : The method of Aspect 765, wherein reduction of VEGF is achieved by treatment with a gene editing means targeting VEGF.

[0774] Aspect 772: The method of Aspect 644, wherein said coinhibitory molecule is human chorionic gonadotropin (hCG).

[0775] Aspect 773: The method of Aspect 772, wherein reduction of hCG is achieved by treatment with a short interfering RNA to hCG.

[0776] Aspect 774: The method of Aspect 772, wherein reduction of hCG is achieved by treatment with a short hairpin RNA to hCG.

[0777] Aspect 775: The method of Aspect 772, wherein reduction of hCG is achieved by treatment with an antisense oligonucleotide to hCG.

[0778] Aspect 776: The method of Aspect 772, wherein reduction of hCG is achieved by treatment with a hammerhead ribozyme to hCG.

[0779] Aspect 777: The method of Aspect 772, wherein reduction of hCG is achieved by treatment with a ribozyme to hCG.

[0780] Aspect 778: The method of Aspect 772, wherein reduction of hCG is achieved by treatment with a gene editing means targeting hCG.

[0781] Aspect 779: The method of Aspect 644, wherein said coinhibitory molecule is progesterone induced blocking factor (PIBF).

[0782] Aspect 780: The method of Aspect 779, wherein reduction of PIBF is achieved by treatment with a short interfering RNA to PIBF.

[0783] Aspect 781 : The method of Aspect 779, wherein reduction of PIBF is achieved by treatment with a short hairpin RNA to PIBF.

[0784] Aspect 782: The method of Aspect 779, wherein reduction of PIBF is achieved by treatment with an antisense oligonucleotide to PIBF.

[0785] Aspect 783: The method of Aspect 779, wherein reduction of PIBF is achieved by treatment with a hammerhead ribozyme to PIBF.

[0786] Aspect 784: The method of Aspect 779, wherein reduction of PIBF is achieved by treatment with a ribozyme to PIBF.

[0787] Aspect 785: The method of Aspect 779, wherein reduction of PIBF is achieved by treatment with a gene editing means targeting PIBF.

[0788] Aspect 786: The method of Aspect 644, wherein said coinhibitory molecule is PD-L1.

[0789] Aspect 787: The method of Aspect 786, wherein reduction of PD-L1 is achieved by treatment with a short interfering RNA to PD-L1.

[0790] Aspect 788: The method of Aspect 786, wherein reduction of PD-L1 is achieved by treatment with a short hairpin RNA to PD-L1.

[0791] Aspect 789: The method of Aspect 786, wherein reduction of PD-L1 is achieved by treatment with an antisense oligonucleotide to PD-L1.

[0792] Aspect 790: The method of Aspect 786, wherein reduction of PD-L1 is achieved by treatment with a hammerhead ribozyme to PD-L1.

[0793] Aspect 791 : The method of Aspect 786, wherein reduction of PD-L1 is achieved by treatment with a ribozyme to PD-L1.

[0794] Aspect 792: The method of Aspect 786, wherein reduction of PD-L1 is achieved by treatment with a gene editing means targeting PD-L1.

[0795] Aspect 793: The method of Aspect 644, wherein said coinhibitory molecule is PD-L2.

[0796] Aspect 794: The method of Aspect 793, wherein reduction of PD-L2 is achieved by treatment with a short interfering RNA to PD-L2.

[0797] Aspect 795: The method of Aspect 793, wherein reduction of PD-L2 is achieved by treatment with a short hairpin RNA to PD-L2.

[0798] Aspect 796: The method of Aspect 793, wherein reduction of PD-L2 is achieved by treatment with an antisense oligonucleotide to PD-L2.

[0799] Aspect 797: The method of Aspect 793, wherein reduction of PD-L2 is achieved by treatment with a hammerhead ribozyme to PD-L2.

[0800] Aspect 798: The method of Aspect 793, wherein reduction of PD-L2 is achieved by treatment with a ribozyme to PD-L2.

[0801] Aspect 799: The method of Aspect 793, wherein reduction of PD-L2 is achieved by treatment with a gene editing means targeting PD-L2.

[0802] Aspect 800: The method of Aspect 644, wherein said coinhibitory molecule is ILT4.

[0803] Aspect 801 : The method of Aspect 800, wherein reduction of ILT4 is achieved by treatment with a short interfering RNA to ILT4.

[0804] Aspect 802: The method of Aspect 800, wherein reduction of ILT4 is achieved by treatment with a short hairpin RNA to ILT4.

[0805] Aspect 803: The method of Aspect 800, wherein reduction of ILT4 is achieved by treatment with an antisense oligonucleotide to ILT4.

[0806] Aspect 804: The method of Aspect 800, wherein reduction of ILT4 is achieved by treatment with a hammerhead ribozyme to ILT4.

[0807] Aspect 805: The method of Aspect 800, wherein reduction of ILT4 is achieved by treatment with a ribozyme to ILT4.

[0808] Aspect 806: The method of Aspect 800, wherein reduction of ILT4 is achieved by treatment with a gene editing means targeting ILT4.

[0809] Aspect 807: The method of Aspect 644, wherein said coinhibitory molecule is HVEM.

[0810] Aspect 808: The method of Aspect 807, wherein reduction of HVEM is achieved by treatment with a short interfering RNA to HVEM.

[0811] Aspect 809: The method of Aspect 807, wherein reduction of HVEM is achieved by treatment with a short hairpin RNA to HVEM.

[0812] Aspect 810: The method of Aspect 807, wherein reduction of HVEM is achieved by treatment with an antisense oligonucleotide to HVEM.

[0813] Aspect 811 : The method of Aspect 807, wherein reduction of HVEM is achieved by treatment with a hammerhead ribozyme to HVEM.

[0814] Aspect 812: The method of Aspect 807, wherein reduction of HVEM is achieved by treatment with a ribozyme to HVEM.

[0815] Aspect 813: The method of Aspect 807, wherein reduction of HVEM is achieved by treatment with a gene editing means targeting HVEM.

[0816] Aspect 814: The method of Aspect 644, wherein said coinhibitory molecule is B7H3.

[0817] Aspect 815: The method of Aspect 814, wherein reduction of B7H3 is achieved by treatment with a short interfering RNA to B7H3.

[0818] Aspect 816: The method of Aspect 814, wherein reduction of B7H3 is achieved by treatment with a short hairpin RNA to B7H3.

[0819] Aspect 817: The method of Aspect 814, wherein reduction of B7H3 is achieved by treatment with an antisense oligonucleotide to B7H3.

[0820] Aspect 818: The method of Aspect 814, wherein reduction of B7H3 is achieved by treatment with a hammerhead ribozyme to B7H3.

[0821] Aspect 819: The method of Aspect 814, wherein reduction of B7H3 is achieved by treatment with a ribozyme to B7H3.

[0822] Aspect 820: The method of Aspect 814, wherein reduction of B7H3 is achieved by treatment with a gene editing means targeting B7H3.

[0823] Aspect 821 : The method of Aspect 644, wherein said coinhibitory molecule is B7H4.

[0824] Aspect 822: The method of Aspect 821, wherein reduction of B7H4 is achieved by treatment with a short interfering RNA to B7H4.

[0825] Aspect 823: The method of Aspect 821, wherein reduction of B7H4 is achieved by treatment with a short hairpin RNA to B7H4.

[0826] Aspect 824: The method of Aspect 821, wherein reduction of B7H4 is achieved by treatment with an antisense oligonucleotide to B7H4.

[0827] Aspect 825: The method of Aspect 821, wherein reduction of B7H4 is achieved by treatment with a hammerhead ribozyme to B7H4.

[0828] Aspect 826: The method of Aspect 821, wherein reduction of B7H4 is achieved by treatment with a ribozyme to B7H4.

[0829] Aspect 827: The method of Aspect 821, wherein reduction of B7H4 is achieved by treatment with a gene editing means targeting B7H4.

[0830] Aspect 828: The method of Aspect 641, wherein said dendritic cell is a myeloid dendritic cell engineered to possess an enhanced amount of one or more costimulatory molecules as compared to a naive dendritic cell.

[0831] Aspect 829: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of CD40 by at least 25%.

[0832] Aspect 830: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of CD40 by at least 50%.

[0833] Aspect 831 : The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of CD40 by at least 100%.

[0834] Aspect 832: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of CD80 by at least 25%.

[0835] Aspect 833: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of CD80 by at least 50%.

[0836] Aspect 834: The method of claim 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of CD80 by at least 100%.

[0837] Aspect 835: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of CD86 by at least 25%.

[0838] Aspect 836: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of CD86 by at least 50%.

[0839] Aspect 837: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of CD86 by at least 100%.

[0840] Aspect 838: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of CD86 by at least 25%.

[0841] Aspect 839: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of CD86 by at least 50%.

[0842] Aspect 840: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of CD86 by at least 100%.

[0843] Aspect 841 : The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of ICOS ligand by at least 25%.

[0844] Aspect 842: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of ICOS ligand by at least 50%.

[0845] Aspect 843: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of ICOS ligand by at least 100%.

[0846] Aspect 844: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of CD70 by at least 25%.

[0847] Aspect 845: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of CD70 ligand by at least 50%.

[0848] Aspect 846: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of CD70 ligand by at least 100%.

[0849] Aspect 847: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of 0X40 by at least 25%.

[0850] Aspect 848: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of 0X40 ligand by at least 50%.

[0851] Aspect 849: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of 0X40 ligand by at least 100%.

[0852] Aspect 850: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of 4.1 BB ligand by at least 25%.

[0853] Aspect 851 : The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of 4.1 BB ligand by at least 50%.

[0854] Aspect 852: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of 4.1 BB ligand by at least 100%.

[0855] Aspect 853: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of GITR ligand by at least 25%.

[0856] Aspect 854: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of GITR ligand by at least 50%.

[0857] Aspect 855: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of GITR ligand by at least 100%.

[0858] Aspect 856: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of LIGHT by at least 25%.

[0859] Aspect 857: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of LIGHT by at least 50%.

[0860] Aspect 858: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of LIGHT by at least 100%.

[0861] Aspect 859: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of TIM3 by at least 25%.

[0862] Aspect 860: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of TIM3 by at least 50%.

[0863] Aspect 861 : The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of TIM3 by at least 100%.

[0864] Aspect 862: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of TIM4 by at least 25%.

[0865] Aspect 863: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of TIM4 by at least 50%.

[0866] Aspect 864: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of TIM4 by at least 100%.

[0867] Aspect 865: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of ICAM1 by at least 25%.

[0868] Aspect 866: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of ICAM1 by at least 50%.

[0869] Aspect 867: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of ICAM1 by at least 100%.

[0870] Aspect 868: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of LFA-3 by at least 25%.

[0871] Aspect 869: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of LFA-3 by at least 50%.

[0872] Aspect 870: The method of Aspect 828, wherein said dendritic cell is treated with TNF alpha at a concentration and duration to increase expression of LFA-3 by at least 100%.

[0873] Aspect 871 : The method of Aspect 641, wherein said dendritic cell is a myeloid dendritic cell engineered to possess an enhanced amount of one or more costimulatory molecules as compared to a naive dendritic cell.

[0874] Aspect 872: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of CD40 by at least 25%.

[0875] Aspect 873: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of CD40 by at least 50%.

[0876] Aspect 874: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of CD40 by at least 100%.

[0877] Aspect 875: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of CD80 by at least 25%.

[0878] Aspect 876: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of CD80 by at least 50%.

[0879] Aspect 877: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of CD80 by at least 100%.

[0880] Aspect 878: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of CD86 by at least 25%.

[0881] Aspect 879: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of CD86 by at least 50%.

[0882] Aspect 880: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of CD86 by at least 100%.

[0883] Aspect 881 : The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of CD86 by at least 25%.

[0884] Aspect 882: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of CD86 by at least 50%.

[0885] Aspect 883: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of CD86 by at least 100%.

[0886] Aspect 884: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of ICOS ligand by at least 25%.

[0887] Aspect 885: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of ICOS ligand by at least 50%.

[0888] Aspect 886: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of ICOS ligand by at least 100%.

[0889] Aspect 887: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of CD70 by at least 25%.

[0890] Aspect 888: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of CD70 ligand by at least 50%.

[0891] Aspect 889: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of CD70 ligand by at least 100%.

[0892] Aspect 890: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of 0X40 by at least 25%.

[0893] Aspect 891 : The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of 0X40 ligand by at least 50%.

[0894] Aspect 892: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of 0X40 ligand by at least 100%.

[0895] Aspect 893: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of 4.1 BB ligand by at least 25%.

[0896] Aspect 894: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of 4.1 BB ligand by at least 50%.

[0897] Aspect 895: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of 4.1 BB ligand by at least 100%.

[0898] Aspect 896: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of GITR ligand by at least 25%.

[0899] Aspect 897: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of GITR ligand by at least 50%.

[0900] Aspect 898: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of GITR ligand by at least 100%.

[0901] Aspect 899: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of LIGHT by at least 25%.

[0902] Aspect 900: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of LIGHT by at least 50%.

[0903] Aspect 901 : The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of LIGHT by at least 100%.

[0904] Aspect 902: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of TIM3 by at least 25%.

[0905] Aspect 903: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of TIM3 by at least 50%.

[0906] Aspect 904: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of TIM3 by at least 100%.

[0907] Aspect 905: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of TIM4 by at least 25%.

[0908] Aspect 906: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of TIM4 by at least 50%.

[0909] Aspect 907: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of TIM4 by at least 100%.

[0910] Aspect 908: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of ICAM1 by at least 25%.

[0911] Aspect 909: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of ICAM1 by at least 50%.

[0912] Aspect 910: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of ICAM1 by at least 100%.

[0913] Aspect 911 : The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of LFA-3 by at least 25%.

[0914] Aspect 912: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of LFA-3 by at least 50%.

[0915] Aspect 913: The method of Aspect 871, wherein said dendritic cell is treated with Beta glucan at a concentration and duration to increase expression of LFA-3 by at least 100%.

[0916] Aspect 914: The method of Aspect 641, wherein said dendritic cell is a myeloid dendritic cell engineered to possess an enhanced amount of one or more costimulatory molecules as compared to a naive dendritic cell.

[0917] Aspect 915: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of CD40 by at least 25%.

[0918] Aspect 916: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of CD40 by at least 50%.

[0919] Aspect 917: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of CD40 by at least 100%.

[0920] Aspect 918: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of CD80 by at least 25%.

[0921] Aspect 919: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of CD80 by at least 50%.

[0922] Aspect 920: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of CD80 by at least 100%.

[0923] Aspect 921 : The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of CD86 by at least 25%.

[0924] Aspect 922: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of CD86 by at least 50%.

[0925] Aspect 923: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of CD86 by at least 100%.

[0926] Aspect 924: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of CD86 by at least 25%.

[0927] Aspect 925: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of CD86 by at least 50%.

[0928] Aspect 926: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of CD86 by at least 100%.

[0929] Aspect 927: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of ICOS ligand by at least 25%.

[0930] Aspect 928: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of ICOS ligand by at least 50%.

[0931] Aspect 929: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of ICOS ligand by at least 100%.

[0932] Aspect 930: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of CD70 by at least 25%.

[0933] Aspect 931 : The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of CD70 ligand by at least 50%.

[0934] Aspect 932: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of CD70 ligand by at least 100%.

[0935] Aspect 933: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of 0X40 by at least 25%.

[0936] Aspect 934: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of 0X40 ligand by at least 50%.

[0937] Aspect 935: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of 0X40 ligand by at least 100%.

[0938] Aspect 936: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of 4.1 BB ligand by at least 25%.

[0939] Aspect 937: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of 4.1 BB ligand by at least 50%.

[0940] Aspect 938: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of 4.1 BB ligand by at least 100%.

[0941] Aspect 939: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of GITR ligand by at least 25%.

[0942] Aspect 940: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of GITR ligand by at least 50%.

[0943] Aspect 941 : The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of GITR ligand by at least 100%.

[0944] Aspect 942: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of LIGHT by at least 25%.

[0945] Aspect 943: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of LIGHT by at least 50%.

[0946] Aspect 944: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of LIGHT by at least 100%.

[0947] Aspect 945: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of TIM3 by at least 25%.

[0948] Aspect 946: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of TIM3 by at least 50%.

[0949] Aspect 947: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of TIM3 by at least 100%.

[0950] Aspect 948: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of TIM4 by at least 25%.

[0951] Aspect 949: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of TIM4 by at least 50%.

[0952] Aspect 950: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of TIM4 by at least 100%.

[0953] Aspect 951 : The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of ICAM1 by at least 25%.

[0954] Aspect 952: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of ICAM1 by at least 50%.

[0955] Aspect 953: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of ICAM1 by at least 100%.

[0956] Aspect 954: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of LFA-3 by at least 25%.

[0957] Aspect 955: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of LFA-3 by at least 50%.

[0958] Aspect 956: The method of Aspect 914, wherein said dendritic cell is treated with Interferon gamma at a concentration and duration to increase expression of LFA-3 by at least 100%.

[0959] Aspect 957: The method of Aspect 641, wherein said dendritic cell is a myeloid dendritic cell engineered to possess an enhanced amount of one or more costimulatory molecules as compared to a naive dendritic cell.

[0960] Aspect 958: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of CD40 by at least 25%.

[0961] Aspect 959: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of CD40 by at least 50%.

[0962] Aspect 960: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of CD40 by at least 100%.

[0963] Aspect 961 : The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of CD80 by at least 25%.

[0964] Aspect 962: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of CD80 by at least 50%.

[0965] Aspect 963: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of CD80 by at least 100%.

[0966] Aspect 964: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of CD86 by at least 25%.

[0967] Aspect 965: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of CD86 by at least 50%.

[0968] Aspect 966: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of CD86 by at least 100%.

[0969] Aspect 967: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of CD86 by at least 25%.

[0970] Aspect 968: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of CD86 by at least 50%.

[0971] Aspect 969: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of CD86 by at least 100%.

[0972] Aspect 970: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of ICOS ligand by at least 25%.

[0973] Aspect 971 : The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of ICOS ligand by at least 50%.

[0974] Aspect 972: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of ICOS ligand by at least 100%.

[0975] Aspect 973: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of CD70 by at least 25%.

[0976] Aspect 974: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of CD70 ligand by at least 50%.

[0977] Aspect 975: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of CD70 ligand by at least 100%.

[0978] Aspect 976: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of 0X40 by at least 25%.

[0979] Aspect 977: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of 0X40 ligand by at least 50%.

[0980] Aspect 978: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of 0X40 ligand by at least 100%.

[0981] Aspect 979: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of 4.1 BB ligand by at least 25%.

[0982] Aspect 980: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of 4.1 BB ligand by at least 50%.

[0983] Aspect 981 : The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of 4.1 BB ligand by at least 100%.

[0984] Aspect 982: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of GITR ligand by at least 25%.

[0985] Aspect 983: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of GITR ligand by at least 50%.

[0986] Aspect 984: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of GITR ligand by at least 100%.

[0987] Aspect 985: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of LIGHT by at least 25%.

[0988] Aspect 986: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of LIGHT by at least 50%.

[0989] Aspect 987: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of LIGHT by at least 100%.

[0990] Aspect 988: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of TIM3 by at least 25%.

[0991] Aspect 989: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of TIM3 by at least 50%.

[0992] Aspect 990: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of TIM3 by at least 100%.

[0993] Aspect 991 : The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of TIM4 by at least 25%.

[0994] Aspect 992: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of TIM4 by at least 50%.

[0995] Aspect 993: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of TIM4 by at least 100%.

[0996] Aspect 994: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of ICAM1 by at least 25%.

[0997] Aspect 995: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of ICAM1 by at least 50%.

[0998] Aspect 996: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of ICAM1 by at least 100%.

[0999] Aspect 997: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of LFA-3 by at least 25%.[001000] Aspect 998: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of LFA-3 by at least 50%.[001001] Aspect 999: The method of Aspect 957, wherein said dendritic cell is treated with HMGB1 at a concentration and duration to increase expression of LFA-3 by at least 100%.[001002] Aspect 1000: The method of Aspect 180, wherein said antigen presenting cell is a B cell.[001003] Aspect 1001 : The method of Aspect 1000, wherein said B cell expresses HLAI.[001004] Aspect 1002: The method of Aspect 1000, wherein said B cell expresses HLAII.[001005] Aspect 1003: The method of Aspect 1000, wherein said B cell expresses one or more costimulatory molecules.[001006] Aspect 1004: The method of Aspect 180, wherein said antigen presenting cell is a neutrophil.[001007] Aspect 1005: The method of Aspect 180, wherein said antigen presenting cell is a type 1 neutrophil.[001008] Aspect 1006: The method of Aspect 180, wherein said antigen presenting cell is a fibroblast.[001009] Aspect 1007: The method of Aspect 180, wherein said antigen presenting cell is a neutrophil transfected with transporter associated protein- 1.[001010] Aspect 1008: The method of Aspect 180, wherein said antigen presenting cell is an astrocyte.[001011] Aspect 1009: The method of Aspect 180, wherein said antigen presenting cell is an endothelial cell.[001012] Aspect 1010: The method of Aspect 1004, wherein said neutrophil is generated form a pluripotent stem cell.[001013] Aspect 1011 : The method of Aspect 1004, wherein said neutrophil is generated form a myeloid progenitor cell.[001014] Aspect 1012: The method of Aspect 1011, wherein said neutrophil is engineered to possess enhanced expression of costimulatory molecules as compared to wild type neutrophils.[001015] Aspect 1013: The method of Aspect 1012, wherein said costimulatory molecule is IL-12 p35.[001016] Aspect 1014: The method of Aspect 1012, wherein said costimulatory molecule is IL-12 p40.[001017] Aspect 1015: The method of Aspect 1012, wherein said costimulatory molecule is IL-12 heterodimer.[001018] Aspect 1016: The method of Aspect 1012, wherein said costimulatory molecule is IL-15.[001019] Aspect 1017: The method of Aspect 1012, wherein said costimulatory molecule is IL-18.[001020] Aspect 1018: The method of Aspect 1012, wherein said costimulatory molecule is CD40.[001021] Aspect 1019: The method of Aspect 1012, wherein said costimulatory molecule is CD80.[001022] Aspect 1020: The method of Aspect 1012, wherein said costimulatory molecule is CD86.BRIEF DESCRIPTION OF THE DRAWINGS[001023] Figure l is a bar graph showing the optimization of senescence induction by doxorubicin protocol (Beta Gal).[001024] Figure 2 is a bar graph showing the optimization of senescence induction by doxorubicin protocol (pl 6).[001025] Figure 3 is a bar graph showing the optimization of senescence induction by doxorubicin protocol (HMGB1).[001026] Figure 4 is a bar graph showing the results of CD40 in an allogeneic mixed lymphocyte reaction performed by culture with 25k, 50k and 100k DC to 100k allogeneic lymphocytes.[001027] Figure 5 is a bar graph showing the results of CD80 in an allogeneic mixed lymphocyte reaction performed by culture with 25k, 50k and 100k DC to 100k allogeneic lymphocytes.[001028] Figure 6 is a bar graph showing the results of CD86 in an allogeneic mixed lymphocyte reaction performed by culture with 25k, 50k and 100k DC to 100k allogeneic lymphocytes.[001029] Figure 7 is a bar graph showing the results of the allostimulatory capacity of DC.[001030] Figure 8 is a bar graph showing the viability of SENOVAX™ after pulsing with lysate.[001031] Figure 9 is a bar graph showing pl6 expression from DCs.[001032] Figure 10 is a bar graph showing suppression of LLC tumor growth by single administration of SENOVAX™ (5 day culture).[001033] Figure 11 is a bar graph showing suppression of LLC tumor growth by single administration of SENOVAX™ (7 day culture).[001034] Figure 12 is a bar graph showing suppression of LLC tumor growth by multiple administrations of SENOVAX™ (5 day culture).[001035] Figure 13 is a bar graph showing suppression of LLC tumor growth by multiple administrations of SENOVAX™ (7 day culture).[001036] Figure 14 is a bar graph showing tumor reduction utilizing B cells pulsed with senescent cell antigens.[001037] Figure 15 is a bar graph showing IL-11 reduction utilizing B cells pulsed with senescent cell antigens.DETAILED DESCRIPTION[001038] The detailed description set forth below is intended as a description of various configurations of the subject technology and is not intended to represent the only configurations in which the subject technology may be practiced. The detailed descriptionincludes specific details for the purpose of providing an understanding of the subject technology. It will be apparent to those skilled in the art that the subject technology may be practiced without these specific details.[001039] The invention provides cell compositions and methods of use thereof that are applicable in oncology for overcoming the limitations to current therapeutic approaches imposed by the tumor microenvironment. One such therapeutic limitation is imposed by the presence of senescent cells. Specifically, the invention provides methods for reducing the numbers or activity of senescent cells in the tumor microenvironment of a subject. The methods of the invention are applicable for targeting or eradicating specific cells in the body of a subject using cell-based vaccines, wherein the cells in the body that are being targeted or eradicated using the methods of the invention are defined by one or a plurality of the following characteristics upon isolated from a subject and evaluated ex vivo-, a) irreversible cell-cycle arrest; (b) a senescence-associated secretory phenotype (SASP); (c) macromolecular damage; and (d) an altered metabolism.[001040] Unless defined otherwise, the technical terms used herein have the same meaning as is commonly understood by one of skill in the art.[001041] " Activation," as used herein, refers to the state of a T cell that has been sufficiently stimulated to induce detectable cellular proliferation. Activation can also be associated with induced cytokine production, and detectable effector functions. The term "activated T cells" refers to, among other things, T cells that are undergoing cell division.[001042] "Administering" as used herein, refers to the physical introduction of an agent to a subject, using any of the various methods and delivery systems known to those skilled in the art. Exemplary routes of administration for the formulations disclosed herein include intravenous, intramuscular, subcutaneous, intraperitoneal, spinal or other parenteral routes of administration, for example by injection or infusion. The phrase "parenteral administration" as used herein means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intralymphatic, intralesional, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal, epidural and intrasternal injection and infusion, as well as in vivo electroporation. In someembodiments, the formulation is administered via a non-parenteral route, e.g., orally. Other non-parenteral routes include a topical, epidermal or mucosal route of administration, for example, intranasally, vaginally, rectally, sublingually or topically. Administering can also be performed, for example, once, a plurality of times, and / or over one or more extended periods.[001043] The term "antigen" as used herein is defined as a molecule that provokes an immune response. This immune response may involve either antibody production, or the activation of specific immunologically competent cells, or both. The skilled artisan will understand that any macromolecule, including virtually all proteins or peptides, can serve as an antigen. Furthermore, antigens can be derived from recombinant or genomic DNA. A skilled artisan will understand that any DNA, which comprises a nucleotide sequence or a partial nucleotide sequence encoding a protein that elicits an immune response therefore encodes an "antigen" as that term is used herein. Furthermore, one skilled in the art will understand that an antigen need not be encoded solely by a full-length nucleotide sequence of a gene. It is readily apparent that the present invention includes, but is not limited to, the use of partial nucleotide sequences of more than one gene and that these nucleotide sequences are arranged in various combinations to elicit the desired immune response. Moreover, a skilled artisan will understand that an antigen need not be encoded by a "gene" at all. It is readily apparent that an antigen can be generated synthesized or can be derived from a biological sample. Such a biological sample can include, but is not limited to a tissue sample, a tumor sample, a cell or a biological fluid.[001044] The term "anti-tumor effect" or “anti-tumor response” as used herein, refers to a biological effect which can be manifested by a decrease in tumor volume, a decrease in the number of tumor cells, a decrease in the number of metastases, an increase in life expectancy, or amelioration of various physiological symptoms associated with the cancerous condition. An "anti-tumor effect" can also be manifested by the ability of the peptides, polynucleotides, cells and antibodies of the invention in prevention of the occurrence of tumor in the first place.[001045] As used herein, the term "autologous" is meant to refer to any material derived from the same individual to which it is later to be re-introduced into the individual.[001046] "Allogeneic" refers to a graft, cell, tissue or organ derived from a different animal of the same species.[001047] The term "cancer" as used herein is defined as disease characterized by the rapid and uncontrolled growth of aberrant cells. Cancer cells can spread locally or through the bloodstream and lymphatic system to other parts of the body. Examples of various cancers include but are not limited to, breast cancer, prostate cancer, ovarian cancer, cervical cancer, skin cancer, pancreatic cancer, colorectal cancer, renal cancer, liver cancer, brain cancer, lymphoma, leukemia, lung cancer and the like. Other specific types of cancer include carcinoma, acinous carcinoma, adenocystic carcinoma, adenoid cystic carcinoma, carcinoma adenomatosum, carcinoma of adrenal cortex, alveolar carcinoma, alveolar cell carcinoma, basal cell carcinoma, carcinoma basocellulare, basaloid carcinoma, basosquamous cell carcinoma, bronchioalveolar carcinoma, bronchiolar carcinoma, bronchogenic carcinoma, cerebriform carcinoma, cholangiocellular carcinoma, chorionic carcinoma, colloid carcinoma, comedo carcinoma, corpus carcinoma, cribriform carcinoma, carcinoma en cuirasse, carcinoma cutaneum, cylindrical carcinoma, cylindrical cell carcinoma, duct carcinoma, carcinoma durum, embryonal carcinoma, encephaloid carcinoma, epiennoid carcinoma, carcinoma epitheliale adenoides, exophytic carcinoma, carcinoma ex ulcere, carcinoma fibrosum, gelatiniform carcinoma, gelatinous carcinoma, giant cell carcinoma, signet-ring cell carcinoma, carcinoma simplex, small-cell carcinoma, solanoid carcinoma, spheroidal cell carcinoma, spindle cell carcinoma, carcinoma spongiosum, squamous carcinoma, squamous cell carcinoma, string carcinoma, carcinoma telangiectaticum, carcinoma telangiectodes, transitional cell carcinoma, carcinoma tuberosum, tuberous carcinoma, verrmcous carcinoma, carcinoma villosum, carcinoma gigantocellulare, glandular carcinoma, granulosa cell carcinoma, hair-matrix carcinoma, hematoid carcinoma, hepatocellular carcinoma, Hurthle cell carcinoma, hyaline carcinoma, hypemephroid carcinoma, infantile embryonal carcinoma, carcinoma in situ, intraepidermal carcinoma, intraepithelial carcinoma, Krompecher's carcinoma, Kulchitzky-cell carcinoma, large-cell carcinoma, lenticular carcinoma, carcinoma lenticulare, lipomatous carcinoma, lymphoepithelial carcinoma, carcinoma medullare, medullary carcinoma, melanotic carcinoma, carcinoma molle, mucinous carcinoma, carcinoma muciparum, carcinoma mucocellulare, mucoepidermoid carcinoma, carcinoma mucosum, mucous carcinoma, carcinoma myxomatodes, naspharyngeal carcinoma, oat cell carcinoma, carcinomaossificans, osteoid carcinoma, papillary carcinoma, periportal carcinoma, preinvasive carcinoma, prickle cell carcinoma, pultaceous carcinoma, renal cell carcinoma of kidney, reserve cell carcinoma, carcinoma sarcomatodes, Schneiderian carcinoma, scirrhous carcinoma, and carcinoma scroti, The term "sarcoma" generally refers to a tumor which is made up of a substance like the embryonic connective tissue and is generally composed of closely packed cells embedded in a fibrillar, heterogeneous, or homogeneous substance. Sarcomas include, chondrosarcoma, fibrosarcoma, lymphosarcoma, melanosarcoma, myxosarcoma, osteosarcoma, endometrial sarcoma, stromal sarcoma, Ewing's sarcoma, fascial sarcoma, fibroblastic sarcoma, giant cell sarcoma, Abernethy's sarcoma, adipose sarcoma, liposarcoma, alveolar soft part sarcoma, ameloblastic sarcoma, botryoid sarcoma, chloroma sarcoma, chorio carcinoma, embryonal sarcoma, Wilns' tumor sarcoma, granulocytic sarcoma, Hodgkin's sarcoma, idiopathic multiple pigmented hemorrhagic sarcoma, immunoblastic sarcoma of B cells, lymphoma, immunoblastic sarcoma of T-cells, Jensen's sarcoma, Kaposi's sarcoma, Kupffer cell sarcoma, angiosarcoma, leukosarcoma, malignant mesenchymoma sarcoma, parosteal sarcoma, reticulocytic sarcoma, Rous sarcoma, serocystic sarcoma, synovial sarcoma, and telangiectaltic sarcoma. Additional exemplary neoplasias include, for example, Hodgkin's Disease, Non-Hodgkin's Lymphoma, multiple myeloma, neuroblastoma, breast cancer, ovarian cancer, lung cancer, rhabdomyosarcoma, primary thrombocytosis, primary macroglobulinemia, small-cell lung tumors, primary brain tumors, stomach cancer, colon cancer, malignant pancreatic insulanoma, malignant carcinoid, premalignant skin lesions, testicular cancer, lymphomas, thyroid cancer, neuroblastoma, esophageal cancer, genitourinary tract cancer, malignant hypercalcemia, cervical cancer, endometrial cancer, and adrenal cortical cancer.[001048] "Costimulatory ligand" as used herein, includes a molecule on an antigen presenting cell that specifically binds a cognate co-stimulatory molecule on a T cell. Binding of the costimulatory ligand provides a signal that mediates a T cell response, including, but not limited to, proliferation, activation, differentiation, and the like. A costimulatory ligand induces a signal that is in addition to the primary signal provided by a stimulatory molecule, for instance, by binding of a T cell receptor (TCR) / CD3 complex with a major histocompatibility complex (MHC) molecule loaded with peptide. A costimulatory ligand can include, but is not limited to, CD7, B7-1 (CD80), B7-2 (CD86), programmed death (PD) LI, PD-L2, 4- IBB ligand, 0X40 ligand, inducible costimulatoryligand (ICOS-L), intercellular adhesion molecule (ICAM), CD30 ligand, CD40, CD70, CD83, human leukocyte antigen G (HLA-G), MHC class I chain-related protein A (MICA), MHC class I chain-related protein B (MICB), herpes virus entry mediator (HVEM), lymphotoxin beta receptor, 3 / TR6, immunoglobulin-like transcript (ILT) 3, ILT4, an agonist or antibody that binds Toll ligand receptor and a ligand that specifically binds with B7-H3. A co-stimulatory ligand includes, without limitation, an antibody that specifically binds with a co-stimulatory molecule present on a T cell, such as, but not limited to, CD27, CD28, 4-1BB, 0X40, CD30, CD40, PD-1, ICOS, lymphocyte function- associated antigen-1 (LFA-1), CD2, CD7, tumor necrosis factor superfamily member 14 (TNFSF14 or LIGHT), natural killer cell receptor C (NKG2C), B7-H3, and a ligand that specifically binds with CD83.[001049] “Cytokine," as used herein, refers to a non-antibody protein that is released by one cell in response to contact with a specific antigen, wherein the cytokine interacts with a second cell to mediate a response in the second cell. A cytokine can be endogenously expressed by a cell or administered to a subject. Cytokines may be released by immune cells, including macrophages, B cells, T cells, and mast cells to propagate an immune response. Cytokines can induce various responses in the recipient cell. Cytokines can include homeostatic cytokines, chemokines, pro-inflammatory cytokines, effectors, and acute-phase proteins. For example, homeostatic cytokines, including interleukin (IL) 7 and IL- 15, promote immune cell survival and proliferation, and pro-inflammatory cytokines can promote an inflammatory response. Examples of homeostatic cytokines include, but are not limited to, IL-2, IL-4, IL-5, IL-7, IL-10, IL-12p40, IL-12p70, IL-15, and interferon (IFN) gamma. Examples of pro-inflammatory cytokines include, but are not limited to, IL-la, IL-lb, IL-6, IL-13, IL-17a, tumor necrosis factor (TNF)-alpha, TNF-beta, fibroblast growth factor (FGF) 2, granulocyte macrophage colony-stimulating factor (GM-CSF), soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular adhesion molecule 1 (sVCAM-1), vascular endothelial growth factor (VEGF), VEGF-C, VEGF-D, and placental growth factor (PLGF). Examples of effectors include, but are not limited to, granzyme A, granzyme B, soluble Fas ligand (sFasL), and perforin. Examples of acute phase-proteins include, but are not limited to, C-reactive protein (CRP) and serum amyloid A (SAA).[001050] A "disease" is a state of health of an animal wherein the animal cannot maintain homeostasis, and wherein if the disease is not ameliorated then the animal's health continues to deteriorate. In contrast, a "disorder" in an animal is a state of health in which the animal is able to maintain homeostasis, but in which the animal's state of health is less favorable than it would be in the absence of the disorder. Left untreated, a disorder does not necessarily cause a further decrease in the animal's state of health.[001051] " Isolated" means altered or removed from the natural state. For example, a nucleic acid or a peptide naturally present in a living animal is not "isolated," but the same nucleic acid or peptide partially or completely separated from the coexisting materials of its natural state is "isolated." An isolated nucleic acid or protein can exist in substantially purified form, or can exist in a non-native environment such as, for example, a host cell.[001052] The term “lymphocyte” means T cells, B cells, NK cells, and Lymphokine Activated Killer (LAK) cells. T-lymphocytes possess T-cell receptors, B -lymphocytes, possess B cell receptors and produce antibodies, Tumor Infiltrating Lymphocytes (TIL) are isolated from tumors and possess some degree of reactivity towards the tumor, cytotoxic T lymphocytes (CTL) are lymphocytes of the CD8 lineage usually and possess ability to kill cells through perforin and / or granzymes. CTL isolation means are described in numerous references including U.S. Pat. No. 6,805,861 and U.S. Pat. No. 6,531,451. Any one lymphocyte produces one type of TCR or antibody. Each TCR or antibody has specificity for one particular epitope, or antigen binding site, on its cognate antigen. Specific TCRs or antibodies are encoded by genes that are formed from the rearrangement of DNA in a lymphocyte stem cell that encodes the constant ("C"), joining ("J"), variable ("V") regions, and possibly diversity ("D") regions of the TCR or antibody. Mammals typically possess one-hundred thousand to one-hundred million lymphocytes of different specificities. Upon stimulation of lymphocytes by an antigen, those lymphocytes specific for the antigen undergo clonal amplification. T lymphocytes are formed in the bone marrow, migrate to and mature in the thymus and then enter the peripheral blood and lymphatic circulation. T lymphocytes are subdivided into three distinct types of cells: helper T cells, suppressor T cells, and cytotoxic T cells. T lymphocytes, unlike B lymphocytes, do not produce antibody molecules, but express a heterodimeric cell surface receptor that recognizes peptide fragments of antigenic proteins that are attached toproteins of the major histocompatibility complex (MHC) and expressed on the surfaces of target cells. T lymphocytes include tumor-infiltrating lymphocytes. Cytotoxic T lymphocytes (CTL) are well known in the art and are typically of the CD3+, CD8+, CD4- phenotype. They typically lyse cells that display fragments of foreign antigens associated with class I MHC molecules on their cell surfaces. CTL typically recognize normal cells expressing antigens after infection by viruses or other pathogens; and tumor cells that have undergone transformation and are expressing mutated proteins or are overexpressing normal proteins. Natural Killer (NK) cells are well known in the art. NK cells are a subset of lymphocytes active in the immune system and representing an average 15% of mononuclear cells in human peripheral blood. Among the surface markers used to identify human NK cells is a receptor binding with low affinity to the Fc fragment of IgG antibodies, such as Fc-. gamma, receptor III or CD16 antigen. NK cells have been demonstrated to play an important role in vivo in the defense against tumors, tumor metastases, virus infection, and to regulate normal and malignant hematopoiesis. Lymphokine-activated killer (LAK) cells are well known in the art and are a cytotoxic population of cells which are capable of lysing autologous tumor cells and NK-cell resistant tumor cell lines. Precursors of LAK cells belong to the subpopulation of "null" lymphocytes that bear neither T nor B cell surface markers. In the human these precursor cells are widely found in peripheral blood, lymph nodes, bone marrow and the thoracic duct. Purification of LAK cells, and their generation are described in U.S. Pat. Nos. 5,002,879, 4,849,329 and 4,690,915.[001053] The term "modulating," as used herein, is meant mediating a detectable increase or decrease in the level of a response in a subject compared with the level of a response in the subject in the absence of a treatment or compound, and / or compared with the level of a response in an otherwise identical but untreated subject. The term encompasses perturbing and / or affecting a native signal or response thereby mediating a beneficial therapeutic response in a subject, preferably, a human.[001054] " Parenteral" administration of an immunogenic composition includes, e.g., subcutaneous (s.c.), intravenous (i.v.), intramuscular (i.m.), or intrasternal injection, or infusion techniques.[001055] The terms "patient," "subject," "individual," and the like are used interchangeably herein, and refer to any animal, such as a mammal, or cells thereofwhether in vitro or in situ, amenable to the methods described herein. In certain nonlimiting embodiments, the patient, subject or individual is a human.[001056] By the term "specifically binds," as used herein with respect to an antibody, is meant an antibody which recognizes a specific antigen, but does not substantially recognize or bind other molecules in a sample. For example, an antibody that specifically binds to an antigen from one species may also bind to that antigen from one or more species. However, such cross-species reactivity does not itself alter the classification of an antibody as specific. In another example, an antibody that specifically binds to an antigen may also bind to different allelic forms of the antigen. However, such cross reactivity does not itself alter the classification of an antibody as specific. In some instances, the terms "specific binding" or "specifically binding," can be used in reference to the interaction of an antibody, a protein, or a peptide with a second chemical species, to mean that the interaction is dependent upon the presence of a particular structure (e.g., an antigenic determinant or epitope) on the chemical species; for example, an antibody recognizes and binds to a specific protein structure rather than to proteins generally. If an antibody is specific for epitope "A", the presence of a molecule containing epitope A (or free, unlabeled A), in a reaction containing labeled "A" and the antibody, will reduce the amount of labeled A bound to the antibody.[001057] By the term "stimulation," is meant a primary response induced by binding of a stimulatory molecule (e.g., a TCR / CD3 complex) with its cognate ligand thereby mediating a signal transduction event, such as, but not limited to, signal transduction via the TCR / CD3 complex. Stimulation can mediate altered expression of certain molecules, such as downregulation of TGF-.beta., and / or reorganization of cytoskeletal structures, and the like.[001058] A "stimulatory molecule," as the term is used herein, means a molecule on a T cell that specifically binds with a cognate stimulatory ligand present on an antigen presenting cell.[001059] A "stimulatory ligand," as used herein, means a ligand that when present on an antigen presenting cell (e.g., an artificial APC [7], a dendritic cell, a B-cell, and the like) can specifically bind with a cognate binding partner (referred to herein as a "stimulatory molecule") on a T cell, thereby mediating a primary response by the T cell,including, but not limited to, activation, initiation of an immune response, proliferation, and the like. Stimulatory ligands are well-known in the art and encompass, inter alia, an MHC Class I molecule loaded with a peptide, an anti-CD3 antibody, a superagonist anti- CD28 antibody, and a superagonist anti-CD2 antibody.[001060] The term "subject" is intended to include living organisms in which an immune response can be elicited (e.g., mammals). Examples of subjects include humans, dogs, cats, mice, rats, and transgenic species thereof.[001061] The term "therapeutic" as used herein means a treatment and / or prophylaxis. A therapeutic effect is obtained by suppression, remission, or eradication of a disease state.[001062] The term "therapeutically effective amount" refers to the amount of the subject compound that will elicit the biological or medical response of a tissue, system, or subject that is being sought by the researcher, veterinarian, medical doctor or other clinician. The term "therapeutically effective amount" includes that amount of a compound that, when administered, is sufficient to prevent development of, or alleviate to some extent, one or more of the signs or symptoms of the disorder or disease being treated. The therapeutically effective amount will vary depending on the compound, the disease and its severity and the age, weight, etc., of the subject to be treated.[001063] To "treat" a disease as the term is used herein, means to reduce the frequency or severity of at least one sign or symptom of a disease or disorder experienced by a subject.[001064] The term "transfected" or "transformed" or "transduced" as used herein refers to a process by which exogenous nucleic acid is transferred or introduced into the host cell. A "transfected" or "transformed" or "transduced" cell is one which has been transfected, transformed or transduced with exogenous nucleic acid. The cell includes the primary subject cell and its progeny.[001065] A "vector" is a composition of matter which comprises an isolated nucleic acid and which can be used to deliver the isolated nucleic acid to the interior of a cell. Numerous vectors are known in the art including, but not limited to, linear polynucleotides, polynucleotides associated with ionic or amphiphilic compounds,plasmids, and viruses. Thus, the term "vector" includes an autonomously replicating plasmid or a virus. The term should also be construed to include non-plasmid and non- viral compounds which facilitate transfer of nucleic acid into cells, such as, for example, polylysine compounds, liposomes, and the like. Examples of viral vectors include, but are not limited to, adenoviral vectors, adeno-associated virus vectors, retroviral vectors, and the like.[001066] Throughout this disclosure, various aspects of the invention can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the breadth of the range.[001067] In certain embodiments, the invention provides compositions and methods for alleviating or targeting the senescence-associated cell phenotype (SASP) in a tumor microenvironment in a subject in need thereof, wherein a tumor microenvironment comprises a primary tumor, a metastatic tumor, or tumor cell in blood or a lymph node. In certain embodiments, the SASP contributes to inflammation and tumor growth in a subject, wherein the SASP comprises one or a plurality of the following molecules: a) interleukin-6 (IL-6); b) IL-8; c) IL-1; d) TNF-alpha; e) a TNF receptor; f) an insulin-like growth factor binding protein (IGFBP); g) Cystatin-C; and h) GDF-15. In other embodiments, the SASP comprises one or a plurality of the following types of molecules: a) an interleukin; b) a chemokine; c) a growth factor; d) a secreted protease; and e) a secreted insoluble molecule. In certain embodiments, the SASP comprises one or a plurality of additional molecules selected from the group comprising monocyte chemotactic protein (MCP-1 / CCL2), C-X-C motif chemokine ligand 1 (CXCL1), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), platelet- derived growth factor (PDGF), epidermal growth factor (EGF), TGFalpha, matrix metalloproteinase (MMP1), MMP3, and a bioactive lipid.I l l[001068] In certain embodiments, the invention provides compositions and methods for inducing an immune response against or otherwise targeting the effects of senescent cells on cancer growth and immune evasion. In one embodiment, a composition of the invention comprises a cell vaccine that mediates the reduction or downregulation of one or a plurality of pathways in the immune system. In certain embodiments, a cell vaccine of the invention targets or affects one or a plurality of molecules selected from the group comprising: a) BCL-2 family of proteins (BCL-XL); b) Heat shock proteins including HSP-90; c) Bromodomain containing 4 (BRD4); d) Na / K ATPase; e) Oxidation resistance 1 (OXR1); f) IL-6; g) IL-8; h) IL-1; and i) TNF-alpha.[001069] In certain embodiments, one or plurality of SASP molecules are associated with ageing in a subject, wherein the association with aging is determined based on assessment of the subject by a medical examination, medical testing, or blood testing such as hematological testing, Complete blood counts, or blood chemistry. In certain embodiments, one or a plurality of the following assessments of the subject are performed: a) determination of age; b) measurement of waist circumference; c) measurement of blood pressure (systolic and / or diastolic); d) IL-6 in blood (i.e., blood plasma or serum); e) C-reactive protein (CRP) in blood; e) albumin in blood; f) alkaline phosphatase in blood; g) blood urea nitrogen (BUN); h) evaluation of gait speed; and i) evaluation of grip strength. In certain embodiments, one or more of the assessments are quantified and the one or more assessments are positively associated with aging. In certain embodiments, the one or plurality of assessments are quantitatively correlated with the burden of one or a plurality of SASP molecules in the subject. SASP molecules may be measured using methods known in the art such as proteomic profiling, immunoassays, or blood chemistry assessments, and statistically correlated with one or a plurality of medical assessments and tests performed on the subject.[001070] In certain embodiments, one or plurality of SASP molecules is associated with the size or stage of cancer in a subject (i.e., Stage 1 to Stage 4, wherein Stage 4 is the most advanced or metastatic stage of disease). In certain embodiments, the one or plurality of SASP molecules are positively correlated with the size of a primary tumor in a subject, wherein tumor size is measured using methods known in the art including but not limited to an imaging scan such as a mammogram or ultrasound or 3D imaging. In certain embodiments, the one or plurality of SASP molecules are positively correlate withthe extent of metastasis of a tumor, for example, as assessed by the number of metastatic sites in the subject, or the quantity of metastatic nodules or tumor cells at one or a plurality of metastatic sites in the body of the subject, which may be measured using techniques such as a CT scan, an MRI, a PET scan, a bone scan, metabolic imaging, or a blood test for one or a plurality of tumor markers or circulating tumor cells (CTCs).[001071] In certain embodiments, a positive correlation between a SASP molecule and a subject-related assessment such as a blood test measurement, tumor size, tumor stage, or another factor may be determined using statistical methods such as correlation analysis or regression analysis. In certain embodiments, the determination of a positive correlation between two measured factors is used to indicate the need for treating a subject with a therapeutic method disclosed herein.[001072] In certain embodiments, a specimen of tissue or blood that is collected from a subject is used to quantify the number of senescent cells ex vivo. In other embodiments, senescent cells are quantified in a subject using imaging techniques, e.g., PET imaging with a radiotracer. In a preferred embodiment, senescent cells are quantified in a tumor specimen obtained from a subject. Ex vivo quantification of senescent cells may be performed using one or a plurality of assays or techniques including but not limited to the senescence-associated beta-galactosidase (SA— P-Gal) assay, flow cytometry, high- content image analysis, immunohistochemistry, immunofluorescence assays, quantitative real-time PCR (qRT-PCR), Western blotting, telomere-induced foci (TIF) analysis, cell cycle phase assay (e.g., using dyes such as DAPI or propidium iodide), and EdU / BrdU incorporation assays that measure cell proliferation. In certain embodiments, the one or more assays or techniques for quantifying senescent cells are utilized to measure the cell cycle inhibitors pl6INK4a (pl6), p21WAFl (p21), or both. In certain embodiments, a plurality of markers comprising pl 6, p21, SA-P-Gal and Ki67 are analyzed from a subject. In certain embodiments, immunohistochemical confirmation can be achieved by detection of components of senescence-associated heterochromatin foci (SAHF), including histone variant macroH2A, di- or trimethylated lysine 9 histone H3 (H3K9me2 / 3), heterochromatin protein (HP) 1 a, P and y and high mobility group A (HMGA) proteins, and DNA damage foci such as phosphorylated H2AX (yH2AX). In one embodiment, identification or quantification of senescent cells is determined using a tissue sample obtained from the subject (e.g., a tumor specimen) that is snap-frozen uponcollection or formalin-fixed, paraffin-embedded for subsequent processing and / or sectioning to be analyzed using one or a plurality of techniques. In certain embodiments, the presence of a senescent cell is identified by the absence of a proliferation marker such as Ki67 or BrdU. In certain embodiments, telomere length is measured by qPCR and quantitative fluorescent in situ hybridization (Q-FISH).[001073] In certain embodiments, high expression of one or a plurality of senescence- associated molecules is used to inform treatment of a subject with cancer using the methods of the invention. The level of expression may be discerned by comparing a tissue or specimen that is not affected by disease (i.e., non-cancerous tissue) to a tissue or specimen from the subject with cancer. In certain embodiments, longitudinal monitoring of senescent cells is performed to assess the subject’s response to treatment with a method of the invention.[001074] The invention discloses compositions of antigen presenting cells (APCs) and methods of use thereof as cellular vaccines for inducing immunity against senescent cells in a subject in need thereof. In one embodiment, an antigen presenting cell is a dendritic cell (DC). In other embodiments, an antigen presenting cell is selected from the group comprising: a) a B cell; b) a macrophage; c) a monocyte; d) a neutrophil; e) a natural killer (NK) cell; f) an endothelial cell; g) an epithelial cell; h) a fibroblast; i) an eosinophil; and j) a mast cell. In certain embodiments, a vaccine comprises an APC that expresses one or a plurality of senescence-related antigens or biomarkers, wherein a senescence-related antigen or biomarker comprises an antigen or biomarker that is upregulated during cellular senescence (e.g., pl 6, p21, or others). In certain embodiments, a senescence-related biomarker is selected from the group comprising: a) Senescence- associated beta-galactosidase (SA-Pgal); b) p21; c) DEC1 / DEC2; d) pl6; e) ARF; f) p 15; g) Senescence-associated heterochromatin foci (SAHF); h) Hl / macroH2A / H3.3 / H3metLys9; i) Asfla / HIRA; j) HP1 / HMGA; k) IL-6; 1) IL-8; m) p53; n) telomere-induced foci / DDR; and o) High Mobility Group Box 1 (HMGB1). One or a plurality of biomarkers may be measured in senescent cells using methods known in the art.[001075] In certain embodiments, a vaccine comprises an APC that expresses one or a plurality of antigens from a senescent cell, wherein the one or plurality of antigens comprises a senescence-related antigen. In certain embodiments, a vaccine comprises anAPC that expresses a tumor-specific antigen, a tumor-associated antigen, or a combination thereof. In one embodiment, a tumor-associated antigen comprises an antigen that is expressed in lung cancer selected from the list comprising: a) Carcinoembryonic antigen (CEA); b) Cytokeratin Fragment 19 (CYFRA-21); c) MAGE- A3; d) MAGE-A1; e) PRAME; f) MUC1; g) ERBB2; and h) HER2. In certain embodiments, a DC is engineered or modified to induce expression of one or a plurality of antigens by the APC. In some embodiments, an APC is loaded with one or a plurality of antigens in vitro. In other embodiments, an APC is genetically modified to express one or a plurality of antigens on its surface. In yet other embodiments, one or a plurality of antigens are delivered to DCs using engineered vectors (e.g., lentivirus vectors), that bind to receptors on the DC.[001076] Methods are provided to induce or modify an APC to express or carry one or a plurality of biomarkers or antigens from senescent cells, for example, by pulsing the APC with a lysate or extract from said senescent cells in a manner that induces uptake of antigens from the senescent cell lysate or extract. Methods of the invention provide an APC composition that is suitable for incorporating antigens from senescent cells. Embodiments of the invention provide lysates derived from autologous and allogeneic senescent cells, from primary cells isolated from the tumor of a subject, from primary cells isolated from the tumor microenvironment of a subject (e.g., fibroblasts), and from cell lines. In certain embodiments, a lysate is derived from a senescent cell that has also undergone expansion or modification in vitro.[001077] In certain embodiments, a lysate or extract from a senescent cell is provided to an APC such as a DC, wherein the antigen uptake capabilities of the APC allow one or a plurality of antigens present in the lysate to be taken up by the DC. Subsequently, detection methods such as flow cytometry, proteomics methods, or other techniques are applicable for identifying the one or plurality of antigens within the DC, or expressed on the surface of the DC, or both.[001078] In certain embodiments, the lysate or extract that is applied to the methods of the invention is derived from a cell that has been rendered senescent by exposure to one or a plurality of stimuli that induce oxidative stress. In certain embodiments, a cell has been rendered senescent by exposure to one or a plurality of stimuli or agents from the group comprising: a) ionizing radiation; b) non-ionizing radiation; c) genotoxic drug(s)(e.g., cisplatin, doxorubicin, bleomycin, methotrexate, etoposide, or others); d) demethylating agent(s) (e.g., gemcitabine, decitabine); and e) acetylating agent(s) (e.g., histone acetyltransferases).[001079] Methods are provided to induce or modify an APC to express or carry one or a plurality of biomarkers or antigens from senescent cells, for example, by pulsing the APC with a lysate or extract from said senescent[001080] The prevent invention describes patient-specific cell-based therapies that are useful for treating cancer. In certain embodiments, the invention provides an autologous APC that induces an immune response against senescent cells upon administration to a subject. In certain embodiments, an APC with these capabilities is generated by engineering said APC to express specific antigens, or by pulsing the APC with said antigens in the form of a cellular lysate, and / or selected proteins, peptides, antigens, or neoantigens. In certain embodiments, an APC is pulsed with one or a plurality of antigens derived from an autologous cell, wherein the autologous cell comprises a senescent cell. In certain embodiments, an APC is pulsed with one or a plurality of antigens derived from an allogeneic cell, wherein the allogeneic cell comprises a senescent cell. In certain embodiments, a senescent cell is selected from the group comprising: a) a fibroblast; b) a bone marrow cell; c) an endothelial cell; d) a myeloid cell; e) a macrophage; f) a basal cell; g) a hair follicle cell; h) a pneumocyte; i) an epithelial cell; j) a T cell; k) a B cell; 1) a microglial cell; m) a choroid plexus cell; n) a plasma cell; o) a neuron; p) a neutrophil; q) a spinous cell; r) a smooth muscle cell; s) an NK cell; t) an NK T cell; u) a cardiomyocyte; v) a pericyte; and w) an endothelial progenitor cell.[001081] In other embodiments, the invention provides an allogeneic APC that induces an immune response against senescent cells upon administration to a subject. In certain embodiments, the APC is pulsed with one or a plurality of antigens in the form of a cellular lysate, and / or selected proteins, peptides, antigens, or neoantigens. In certain embodiments, the one or plurality of antigens are derived from a cell source that is autologous. In certain embodiments, the one or plurality of antigens are derived from an allogeneic cell source.[001082] In one embodiment, the invention provides autologous DCs for application as a cellular vaccine, wherein the autologous DCs comprise one or a plurality ofsenescence-related antigen, or biomarkers and wherein the one or plurality of senescence- related antigens or biomarkers are derived from autologous fibroblasts. In certain embodiments, the senescence-related antigens or biomarkers comprise one or a plurality of antigens selected from the group comprising: a) pl 6; b) p21; c) HLA-II; d) HLA-E; e) HCMV-gly coprotein B (HCMV-gB); e) Atypical Chemokine receptor 3 (ACKR3); f) IL- 6; and g) IL-8.[001083] In one embodiment, a method for treating a subject with cancer by targeting senescent cells in the tumor microenvironment using an autologous vaccine is provided, the method comprising: a) identifying a subject with cancer; b) isolating peripheral blood mononuclear cells comprising a precursor cell from the subject; c) inducing in vitro differentiation of the precursor cell into an antigen presenting cell; d) providing the antigen presenting cell with lysate comprising one or a plurality of antigens from a senescent cell, wherein the dendritic cell takes up and incorporates the one or plurality of antigens, and wherein the one or plurality of antigens is selected from the group comprising p l 6Illk4ap21Cipl, and high mobility group box 1 (HMGB1); e) administering a therapeutically effective amount of the antigen presenting cell to the subject, wherein the antigen presenting cell stimulates an immune response against senescent cells in the tumor microenvironment. In some embodiments, the antigen presenting cells are administered subcutaneously. In other embodiments, alternate routes of administration may be used such as intradermal, intramuscular, intrathecal, or intravenous. In certain embodiments, a single administration of the cell vaccine is provided to a subject. In other embodiments, multiple administrations are provided at defined intervals; for example, daily, weekly, or monthly administrations for a period of days, weeks, or months, as appropriate for an individual subject’s treatment regimen. In certain embodiments, the senescent cell used to generate lysate expresses one or plurality of the following biomarkers or antigens selected from the group comprising: a) Senescence-associated beta-galactosidase (SA-Pgal); b) DEC1 / DEC2; c) ARF; d) p 15; e) Senescence-associated heterochromatin foci (SAHF); f) IL-6; g) IL-8; h) TNF-alpha; p53; and i) telomere- induced foci. In certain embodiments, the senescent cell is selected from the group comprising: a) a fibroblast; b) a bone marrow cell; c) an endothelial cell; d) a myeloid cell; e) a macrophage; f) a basal cell; g) a hair follicle cell; h) a pneumocyte; i) an epithelial cell; j) a T cell; k) a B cell; 1) a microglial cell; m) a choroid plexus cell; n) a plasma cell; o) a neuron; p) a neutrophil; q) a spinous cell; r) a smooth muscle cell; s) anNK cell; t) an NK T cell; u) a cardiomyocyte; v) a pericyte; w) an endothelial progenitor cell; x) a tumor cell; and y) a mesenchymal stromal cell. In certain embodiments, the senescent cell comprises a fibroblast. In certain embodiments, the fibroblast comprises a dermal fibroblast. In certain embodiments, the dermal fibroblast is obtained by a punch biopsy of skin from the subject. In other embodiments, the fibroblast is derived from the periphery of a tumor. In certain embodiments, the fibroblast expresses one or a plurality of molecules selected from the group comprising: a) CD11c; b) c-kit; c) c-met; d) OCT-4; e) NANOG; f) KLF4; g) SSEA4; h) TRA-1; i) PIM-1; j) PD-GF receptor; and k) SLC14A4. In certain embodiments, the fibroblast expresses HLA class II antigens. In certain embodiments, the lysate is derived from a cell that is rendered senescent by treatment with doxorubicin, wherein doxorubicin is provided at a concentration between 100 nM and 200 nM. In certain embodiments, the lysate is derived from a cell that is rendered senescent by treatment with one or a plurality of the following stimuli or agents selected from the group comprising: a) ionizing radiation; b) non-ionizing radiation; c) a genotoxic drug; d) a demethylating agent; and e) an acetylating agent. In certain embodiments, the antigen presenting cell is selected from the group comprising: a) a B cell; b) a macrophage; c) a monocyte; d) a neutrophil; e) a natural killer (NK) cell; f) an endothelial cell; g) an epithelial cell; h) a fibroblast; i) an eosinophil; j) a mast cell, and k) a dendritic cell. In other embodiments, the antigen presenting cell is a DC. In certain embodiments, the antigen presenting cell exhibits surface expression of CD80, CD86, and HLA class II molecules.[001084] Embodiments of the invention provide a cell vaccine comprising antigen presenting cells that have functions in targeting cells or cellular functions in the tumor microenvironment. In certain embodiments, the tumor microenvironment comprises cells having the senescence-associated secretory phenotype (SASP). In certain embodiments, the SASP comprises one or a plurality of the following molecules: a) interleukin-6 (IL-6); b) IL-8; c) IL-1; d) TNF-alpha; e) a TNF receptor; f) an insulin-like growth factor binding protein (IGFBP); g) Cystatin-C; and h) GDF-15. In certain embodiments, a cellular vaccine is provided that elicits an immune response against one or a plurality of antigens in the tumor microenvironment. In certain embodiments, the immune response against senescent cells is directed against one or a plurality of the following molecules: a) a member of the BCL-2 family of proteins; b) a Heat Shock protein; c) Bromodomaincontaining 4 (BRD4); d) Na / K ATPase; e) Oxidation resistance 1 (0XR1); f) IL-6; g) IL- 8; h) IL-1; and i) TNF-alpha.[001085] In addition to targeting cells within the tumor or its microenvironment, the compositions and methods of the invention are also useful for targeting tumor cells at sites that are distant from a primary tumor or for systemic targeting of senescent cells contributing to malignancy, disease, and other effects of aging in a subject.[001086] In one embodiment the invention provides treatment of cancers using dendritic cells that have been pulsed with senescent cell antigens. Said antigens are obtained from autologous sources and possess ability to induce immunity to tumor associated senescent cells. In one embodiment the invention provides that administration of lung cancer specific peptides together with senescent cells.[001087] Dendritic cells (DC) were originally identified by Ralph Steinman as bone marrow derived professional antigen presenting cells, being the only cell of the immune system capable of activating naive T cells

[0035] , Subsequent studies have shown that DC act as a critical bridge between the innate immune system, which is constantly patrolling for various “danger” signals such as toll like receptor (TLR) agonists that are associated with tissue injury or pathogenic threat. In contrast to other antigen presenting cells, such as the macrophage or the B cell, DC exhibit a much higher ability to stimulate T cell responses both in antigen specific systems, as well as in polyclonal experiments such as in mixed lymphocyte reaction

[0036] , It is known that in peripheral tissues (outside of lymph nodes), DCs capture antigens through several complementary mechanisms, including phagocytosis and receptor mediated endocytosis. Immature DC are known to possess a high degree of phagocytic activity and low levels of antigen presenting activity. Normally, DCs in peripheral tissues are immature. These immature DCs have the ability to efficiently capture antigens; accumulate MHC class II molecules in the late endosome- lysosomal compartment; express low levels of co-stimulatory molecules; express a unique set of chemokine receptors (such as CCR7) that allow their migration to lymphoid tissues; and they have a limited capacity for secreting cytokines

[0037] ..[001088] Once DC are activated, by a stimulatory signal such as a toll like receptor agonist, phagocytic activity decreases and the DC then migrate into the draining lymph nodes through the afferent lymphatics. During the trafficking process, DC degradeingested proteins into peptides that bind to both MHC class I molecules and MHC class II molecules. This allows the DC to perform the following functions: a) cross presentation in that they ingest exogenous antigens but present peptides in the MHC I pathway; and b) activation of both CD8 (via MHC I) and CD4 (via MHC II). Interestingly, lipid antigens are processed via different pathways and are loaded onto non-classical MHC molecules of the CD1 family

[0038] ,[001089] In some embodiments the invention teaches the use of senescent cell derived exosomes for pulsing dendritic cells to induce immunity to tumor protecting / promoting senescent cells.[001090] Numerous animal models have demonstrated that, in the context of neoplasia, DCs can bind to and engulf tumor antigens that are released from tumor cells, either alive or dying, and cross-present these antigens to T cells in tumor-draining lymph nodes. This results in the generation of tumor-specific immune responses that have been demonstrated to inhibit tumor growth or in some cases induced transferrable immunological memory. Mechanistically, DCs recognize tumors using the same molecular means that they would use to recognize apoptotic cells, or cells that are stressed. One set of signals are molecules released from apoptotic cells, which are highly released by tumors, these include the nucleotides UTP and ATP, fractalkine, lipid lysophosphatidylcholine, and sphingosine 1-phosphate

[0039] , Signals from stressed cells, such as tumor cells, include externalization of phosphatidylserine onto the outside of the cell membrane, calreticulin, avB5 integrin, CD36 and lactadherin. There is some evidence that dendritic cells actively promote tumor immunity in that patients with dendritic cell infiltration of tumors generally have a better prognosis [40-43],[001091] The most advanced DC based therapy is the product Provenge (sipuleucel- T), which is approved by the FDA for treatment of androgen resistant prostate cancer. Provenge is a cellular product derived from autologous peripheral blood mononuclear cell (PBMC) derived dendritic cells that have been grown using a chimeric protein comprised of GM-CSF and the prostate specific antigen, prostatic acid phosphatase [44, 45], In the pivotal trial, this DC based therapeutic resulted in extension of survival by 4.1 months

[0045] , Prior to approval of Provenge, numerous clinical trials using DC were performed in prostate cancer, which will be discussed below.[001092] Tjoa et al reported on 33 participants of a phase I trial in patients with advanced prostate cancer that received autologous DC pulsed HLA-A0201 -specific prostate-specific membrane antigen (PSMA) peptides (PSM-P1 or -P2) that were entered into a second trial (Phase II), which involved six infusions of DC pulsed with PSM-P1 and -P2 peptides. The patients were followed up for up to 770 days from the start of the original phase I study. 9 partial responders were identified in the Phase II study based on National Prostate Cancer Project (NPCP) criteria, plus 50% reduction of prostate-specific antigen. Four of the partial responders were also responders in the Phase I study, with an average response duration of 225 days. Their combined average total response period was over 370 days. Five other responders in the secondary immunizations at the Phase II were nonresponders in the Phase I study. Their average partial response period was 196 days. These data support the safety of follow-up infusion of DC that have been pulsed with tumor antigen derived peptide

[0046] , The same group published a subsequent paper on an additional 33 patients that had not received prior DC immunization in the Phase I. All subjects received six infusions of DC pulsed with PSM-P1 and -P2 at six-week intervals without any treatment associated adverse events. Six partial and two complete responders were identified in the Phase II study based on NPCP criteria, plus 50% reduction of prostate-specific antigen (PSA), or resolution in previously measurable lesions on ProstaScint scan

[0047] , The same group analyzed immune response in patients who had clinical remission or relapsed. A strong correlation was found between delayed type hypersensitivity response to the PSM-P1 and PSM-P2 and clinical response

[0048] ,[001093] The approach that was to evolve into Provenge was described in a paper that reported the outcome of 12 androgen resistant prostate cancer patients treated with DC that were pulsed with a GM-CSF-PAP fusion protein. Two intravenous infusions of the generated cells were performed one month apart. The infusions were followed by three s.c. monthly doses of the fusion protein without cells. Treatment was well tolerated and circulating prostate-specific antigen levels dropped in three patients. Immune response to the fusion protein was observed, as well as to PAP

[0049] , A subsequent study utilized the Provenge approach as used today, that is, without the subcutaneous boosting with protein alone. In this study, DC precursors were harvested by leukapheresis in weeks 0, 4, 8, and 24, loaded ex vivo with antigen for 2 days, and then infused intravenously for over 30 minutes. Phase I patients received increasing doses of Provenge, and Phase II patients received all the Provenge that could be prepared from a leukapheresis product. Patientstolerated treatment well. Fever, the most common adverse event, occurred after 15 infusions (14.7%). All patients developed immune responses to the recombinant fusion protein used to prepare Provenge, and 38% developed immune responses to PAP. Three patients had a more than 50% decline in prostate-specific antigen (PSA) level, and another three patients had 25% to 49% decreases in PSA. The time to disease progression correlated with development of an immune response to PAP and with the dose of dendritic cells received

[0050] , An additional study utilized the same approach to treat 21 patients with histologically documented androgen-independent prostate carcinoma that could be evaluated by radionuclide bone scan or computed tomography scan. Provenge was prepared from a leukapheresis product; it contained autologous CD54-positive recombinant GM-CSF-PAP loaded DC with admixtures of monocytes, macrophages, B and T cells. Provenge was infused intravenously twice, 2 weeks apart. Two weeks after the second infusion, patients received three subcutaneous injections of 1.0 mg of the recombinant protein 1 month apart. Nineteen patients could be evaluated for response to treatment. The median time to progression was 118 days. Treatment was tolerated reasonably well; most adverse effects were secondary to Provenge and were NCI Common Toxicity Criteria Grade 1-2. Four of the 21 patients reported Grade 3-4 adverse events. Two patients exhibited a transient 25-50% decrease in prostate-specific antigen (PSA). For a third patient, PSA dropped from 221 ng / ml at baseline to undetectable levels by week 24 and has remained so for more than 4 years. In addition, this patient's metastatic retroperitoneal and pelvic adenopathy has resolved. PBMC collected from patients for at least 16 weeks proliferated upon in vitro stimulation by the recombinant GM-CSF-PAP. For the patient with responsive disease, PBMC could be stimulated for 96 weeks

[0051] , Another study assessed the effects of Provenge on androgen independent prostate cancer with biochemical progression. This type of cancer is earlier in the oncogenesis process as compared to androgen resistant cancer. Specifically, patients with nonmetastatic recurrent disease as manifested by increasing PSA levels (0.4-6.0 ng / mL) and who had undergone previous definitive surgical or radiation therapy were enrolled. Therapy consisted of Provenge infusions in weeks 0, 2, and 4 (i.e., 3 infusions). Prostatespecific antigen was measured at baseline and monthly until disease progression, defined as a doubling of the baseline or nadir PSA value (whichever was lower) to > or = 4 ng / mL or development of distant metastases. Thirteen of 18 patients demonstrated an increase in PSA doubling time (PSADT), with a median increase of 62% (4.9 months before treatment vs. 7.9 months after treatment; P = 0.09; signed-rank test). These datasuggested that Provenge has therapeutic activity both on androgen dependent, which is more early stage, and androgen dependent, which is more late stage, prostate cancer

[0052] , The Phase III trial for Provenge consisted of 512 randomly assigned prostate cancer patients in a 2: 1 ratio to receive either Provenge (341 patients) or placebo (171 patients) administered intravenously every 2 weeks, for a total of three infusions. The primary end point was overall survival, analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen (PSA) and lactate dehydrogenase. In the Provenge group, there was a relative reduction of 22% in the risk of death as compared with the placebo group (P=0.03). This reduction represented a 4.1- month improvement in median survival (25.8 months in the Provenge group vs. 21.7 months in the placebo group). The 36-month survival probability was 31.7% in the Provenge group versus 23.0% in the placebo group. Immune responses to the immunizing antigen were observed in patients who received Provenge but not controls

[0053] ,[001094] In addition to Provenge, which as mentioned above, received FDA marketing approval, several other types of antigens have been utilized in DC therapy of prostate cancer. For example, while PSA is a known biochemical marker of prostate cancer progression, the PSA protein or peptides from this protein have been identified to possess immunogenic properties. One study examined the possibility of utilizing PSA protein pulsed DC for treatment of prostate cancer. Twenty-four patients with histologically proven prostate carcinoma and an isolated postoperative rise of serum PSA (>1 ng / ml to 10 ng / ml) after radical prostatectomy were included. The patients received nine administrations of PSA-loaded DCs by combined intravenous, subcutaneous, and intradermal routes over 21 weeks. Circulating prostate cancer cells detected in six patients at baseline were undetectable at 6 months and remained undetectable at 12 months. Eleven patients had a postbaseline transient PSA decrease on one to three occasions, predominantly occurring at month 1 (7 patients) or month 3 (2 patients). Maximum PSA decrease ranged from 6% to 39%. PSA decrease on at least one occasion was more frequent in patients with low Gleason score (p=0.016) at prostatectomy and with positive skin tests at study baseline (p=0.04). PSA-specific T cells were detected ex vivo by ELISpot for IFN-gamma in 7 patients before vaccination and in 11 patients after vaccination. Of the latter 11 patients, 5 had detectable T cells both before and during the vaccination period, 4 only during the vaccination period, while 2 patients could for technical reasons not be assessed prevaccination. No induction of anti-PSA IgG or IgMantibodies was detected. There were no serious adverse events or otherwise severe toxi cities observed during the trial

[0054] , Proteins may possess both immune stimulatory and immune inhibitory epitopes. Thus, some studies sought to utilize specific peptides that are known to be immune stimulatory. Accordingly, a clinical trial was conducted in 28 patients with locally advanced or metastatic prostate cancer to determine whether an HLA-A2 binding epitope of prostate-specific antigen, PSA146-154 (PSA-peptide), can induce specific T cell immunity. Patients were vaccinated either by intradermal injection of PSA-peptide and GM-CSF, or by intravenous administration of autologous dendritic cells pulsed with PSA-peptide at weeks 1, 4 and 10. DTH skin testing was performed at weeks 4, 14, 26 and 52. Fifty percent of the patients developed positive DTH responses to PSA-peptide. Cytokine analysis of PSA-peptide stimulated T cells exhibited specific IFN- gamma and TNF-alpha response in six of seven patients. Specific IL-4 response was observed in five patients, while IL-10 response was detected in one patient. Purified CD4- CD8+ T cells isolated from four patients demonstrated specific cytolytic activity per chromium release assay. This trial demonstrated that immunization with PSA-peptide induced specific T cell immunity in one-half of the patients with locally advanced and hormone-sensitive, metastatic prostate cancer. DTH-derived T cells exhibited PSA- peptide-specific cytolytic activity and predominantly expressed a type- 1 cytokine profile

[0055] , A subsequent study sought to boost effects of PSA peptide pulsed DC through administration of interferon gamma in the treatment of 12 hormone resistant prostate cancer patients. All patients were vaccinated four times with intracutaneously injected PSA-peptide loaded DCs after subcutaneous administration of IFN-gamma 2 hr before DC administration (50 microg / m(2) body surface). The vaccination was well tolerated without any vaccination-associated adverse events. One partial and one mixed responder were identified, and four patients showed stable diseases. Two patients had a decrease, and four had a slow-down velocity slope in the PSA serum level. All responders showed a positive DTH-response, but only two showed a slight increase in PSA-peptide specific T- lymphocytes

[0056] , Given that tumors may suppress expression of certain peptides, or alternatively may mutate the peptide, a more global approach towards stimulation of anticancer immunity has been the utilization of multiple peptides to overcome these hurdles. A clinical study in 8 androgen resistant prostate cancer patients utilized a cocktail consisting of HLA-A*0201 -restricted peptides derived from five different prostate cancer-associated antigens [prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), survivin, prostein, transient receptor potential p8 (trp-p8)].Patients were treated with 4 vaccinations of pulsed DC once every two weeks. Apart from local skin reactions, no side effects were noted. One patient displayed a partial response (PR; PSA decrease >50%) and three other patients showed stable PSA values or decelerated PSA increases. In ELISPOT analyses, three of four PSA responders also showed antigen-specific CD8+ T-cell activation against prostein, survivin and PSMA

[0057] , Cocktail approaches have also been used by other investigators using different peptides. For example, a study by Waeckerle-Men et al. utilized autologous DC of HLA- A*0201(+) patients with hormone-refractory prostate cancer that were loaded with antigenic peptides derived from prostate stem cell antigen (PSCA(14-22)), prostatic acid phosphatase (PAP(299-307)), prostate-specific membrane antigen (PSMA(4-12)) and prostate-specific antigen (PSA(154-163)). DC were intradermally applied six times at biweekly intervals followed-in the case of an enhanced immune response-by monthly booster injections. Of the three patients that were reported, the vaccination elicited significant cytotoxic T cell responses against all prostate-specific antigens tested. In addition, memory T cell responses against the control peptides derived from influenza matrix protein and tetanus toxoid were efficiently boosted. Clinically, the long-term DC vaccination was associated with an increase in PSA doubling time

[0058] , In addition to prostate cancer, in which FDA approval has been granted for the Provenge drug, numerous trials have been conducted in a wide variety of cancers. All the trials demonstrated safety, without serious adverse effects of DC administration, as well as some degree of therapeutic efficacy. Trials have been conducted in melanoma [59-110], soft tissue sarcoma

[0111] , thyroid [112-114], glioma [115-136], multiple myeloma ,[137- 145], lymphoma [146-148], leukemia [149-156], as well as liver [157-162], lung [163- 176], ovarian [177-180], and pancreatic cancer [181-183], The tumor microenvironment (TME), consists primarily of the extracellular matrix (ECM), and is considered crucial to various aspects of tumor progression, such as tumorigenesis, metastasis, relapse and treatment resistance, making it a potential target for cancer therapies

[0184] , The TME is a complex system comprising a range of cellular and noncellular elements, and cancer- associated fibroblasts (CAFs), which are highly abundant in the tumor stroma and exhibit potent regulatory effects on tumor growth. The induction of cell senescence through traditional cancer treatments is one of the most notable mechanisms of tumor suppression. In cancer it is accepted that the chronic accumulation of senescent cells promotes tumor development

[0185] , One means by which senescent cells promote cancer growth is through direct and indirect immune suppressive mechanisms. A classically knownmethodology used by tumors for immune escape is recruitment and expansion of myeloid suppressor cells [186-189], It has been published by numerous groups that these cells are effectively recruited and expanded by senescent fibroblasts associated with the tumor microenvironment [190-192],[001095] Tumor associated senescent cells also produce growth factors that enhance tumor growth, metastasis, and drug resistance [193, 194], In one study, it was shown that Chemerin, a previously unreported SASP factor released from senescent human dermal fibroblasts, promotes cancer cell migration, which is a key feature driving tumor progression. Whereas the Chemerin abundance is downregulated in malignant cancer cells, increased Chemerin transcripts and protein concentrations are detected in replicative senescent fibroblasts in vitro and in the fibroblast of skin sections from old donors [195, 196], In another study, clinical samples of primary invasive carcinoma and chemoresistant breast cancer metastasis contain a unique hybrid cancer cell population coexpressing pancytokeratin and the MSC marker fibroblast activation protein-a. We show that hybrid cells form in primary tumors, and that they promote breast cancer metastasis and chemoresistance. Using single-cell microfluidics and in vivo models, we found that there are polyploid senescent cells within the hybrid cell population that contribute to metastatic dissemination. Our data reveal that Wnt Family Member 5A (WNT5A) plays a crucial role in supporting the chemoresistance properties of hybrid cells. Furthermore, we identified that WNT5A mediates hybrid cell formation through a phagocytosis-like mechanism that requires BCC-derived IL-6 and MSC-derived C-C Motif Chemokine Ligand 2. These findings reveal hybrid cell formation as a mechanism of chemoresistance and suggest that interrupting this mechanism may be a strategy in overcoming breast cancer drug resistance.[001096] A recent study involving mice revealed that, with exposure to chemotherapy, senescent cells become resistant to apoptotic stimuli and accumulate in normal tissue. This phenomenon is related to premature aging and therapy-associated feeling of fatigue in patients following chemoradiotherapy

[0197] , Another recent study involving doxorubicin-treated mice shows that there is significant clearance of senescent cells, which not only reduces relapse and metastasis, but also the untoward effects of doxorubicin, such as bone marrow suppression and cardiotoxicity. Thus, selective elimination of accumulated senescent cells through senolytics may be beneficial forpatients treated with chemotherapy to reduce the risk of relapse and drug toxicity

[0198] , Amongst the promising senolytic compounds, the BH3 mimetic inhibitors of the anti- apoptotic Bcl-2 family, the tyrosine kinase inhibitor (TKI) dasatanib and the flavonoid quercetin have shown great promise in the preclinical settings

[0123] , The inhibitors of the Bcl-2 anti-apoptotic members include those targeting Bcl-2, Bcl-W, Bcl-xL and Mcl-1. These drugs target the inhibitory effect of these proteins on processes such as apoptosis and autophagy, which are deregulated in senescent cells [7], These small molecules are designed to target the BH3 domain within Bcl-2, which prevents sequestration of proapoptotic proteins, thus sensitizing cells to death stimuli. Interestingly, by dint of their ability to target senescent cells, Bcl-2 inhibitors are also described as senolytics

[0124] , Furthermore, inhibitors of Bcl-2 family provide additional advantages such as the ability to alleviate age-related diseases like atherosclerosis, increase radioprotection and rejuvenate the hematopoietic system in mice

[0121] , Inhibitors of Bcl-W and Bcl-XL proteins such as ABT-737 induce apoptosis in vitro and in vivo preferentially in senescent cells. Due to poor oral availability, ABT-737 was improved upon by an orally available analog, ABT-263 (navitoclax)

[0123] ; however, due to their off-target toxicity, these two agents have limited clinical utility

[0125] , More recent advances have seen more promising agents, such as ABT199 (venetoclax), which seems highly specific for Bcl-2 as well as A1331852 and Al 155463, which are undergoing clinical evaluation

[0126] , Dasatinib is an anticancer drug with the ability to induce apoptosis and is approved by the Food and Drug Administration. Dasatinib can also be given in combination with quercetin, and this combination drug works as a senolytic approach

[0127] , It is effective in inducing apoptosis of a variety of cell types such as senescent preadipocytes, endothelial cells and mouse embryonic fibroblasts in vitro

[0123] , Studies also show that senolytics improve age-related symptoms such as dystonia, decline in muscle strength and coordination, loss of bladder control30 and bone weakness

[0128] , Ueda et al treated 18 patients with CEA- expressing lung adenocarcinomas who were positive for human leukocyte antigen (HLA)- A24. DCs were generated from the patients' autologous monocyte-enriched fractions of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells in the presence of granulocyte / macrophage colony-stimulating factor and interleukin-4. The generated DCs were pulsed with CEA-derived, HLA-A24-restricted 9-mer peptide (CEA652) and injected into the patients intradermally and subcutaneously every 2 weeks. No severe toxicity directly attributable to the treatment was observed, and the vaccine was well tolerated. Long-term stable disease or marked decreases in the serum CEA levelwere observed in some patients after therapy. Most of the patients in whom treatment was clinically effective showed a positive skin response to CEA652-pulsed DCs (delayed-type hypersensitivity skin test) and a positive in vitro CTL response to CEA652 peptide after therapy

[0163] ,[001097] A subsequent study utilized a similar approach except that instead of a defined peptide, apoptotic bodies of an allogeneic NSCLC cell line that overexpressed Her2 / neu, CEA, WT1, Mage2, and survivin were used as sources of antigen. DCs were partially matured with a factor that induced surface molecule expression but minimal cytokine production. 16 patients with stage 1 A to IIIB NSCLC that were previously treated with conventional therapy were immunized intradermally two times, 1 month apart. There were no unanticipated or serious adverse events. Immunologic responses followed three distinct patterns of reactivity: (1) five of 16 patients showed no clear immunologic response, (2) five of 16 patients showed a tumor-antigen independent response, and (3) six of 16 show an antigen specific response. Immunologic responses were independent of stage and prior therapy. Favorable and unfavorable clinical outcomes were independent of measured immunologic responses

[0164] , This approach appears to be scalable in that the antigenic cell line can be grown up to basically unlimited quantities, and the autologous DC generation was reported to be effective

[0166] , Unfortunately, a subsequent study performing longer follow-up reported no correlation between dosage and response

[0170] , Given the possibility that a tumor cell line as used above may not represent a true in vivo tumor situation, especially given that cell lines lack immunological pressure, Chang et al utilized pleural effusions from late-stage cancer patients as an antigenic source. Eight patients with late-stage non-small cell lung carcinoma were vaccinated once weekly for 4 weeks and then boosted twice biweekly. DCs were generated by culturing adherent mononuclear cells with interleukin-4 and granulocyte-macrophage-colony-stimulating factor for 7 days. Day-7 DCs were cocultured overnight with autologous necrotic tumor cells derived from pleural effusion specimens to allow internalization of tumor antigens. DCs were then treated with tumor necrosis factor-alpha for 16 hours. The antigen-loaded DCs were injected into each patient's inguinal lymph nodes under sonographic guidance. The authors found that there was no Grade II / III toxicity and autoimmune response in all patients after intranodal injection of the DC vaccine. Minor to moderate increases in T-cell responses against tumor antigens were observed after DC vaccination in six of eight patients. Five patientshad progressive disease. One patient had minor tumor response, and two patients had stable disease. The two patients who had longer disease control also had better T-cell responses as compared to pretreatment or to non-clinical responders

[0165] ,[001098] While effusions are easier to extract, they may not represent the true antigenic composition of tumors, especially given the notion that tumor initiating cells (tumor stem cells) are found within hypoxic tissues and these reside intratumorally and would not be effused. Accordingly, a different approach that may be more relevant would be to utilize tumor lysates themselves isolated from resections. Um et al immunized 15 patients with inoperable stage III or IV NSCLC and assigned them to cohorts that received 3, 6, or 12 x 10(6) DC-Vac intradermally 3 times at 2-week intervals. They reported that the maximum dose of the DC vaccine (12 x 10(6)) was shown to be safe. In 5 of 9 patients, the vaccine resulted in increased interferon (IFN)-y production by CD8+ cells after exposure to tumor lysate. Additionally, there were mixed responses that do fulfill progressive disease definition and demonstrate some clinical benefit in two patients

[0173] , Another study utilizing tumor lysates as antigen was reported by a Brazilian group, in which 5 patients with inoperable stage III or IV NSCLC were selected to receive two doses of 5 x 107 DC cells administered subcutaneous and intravenously two times at two-week intervals. The dose of the vaccine has shown to be safe and well tolerated. The lymphoproliferation assay showed an improvement in the specific immune response after the immunization, with a significant response after the second dose. This response was not long lasting and a tendency to reduction two weeks after the second dose of the vaccine was observed. Two patients had a survival almost twice greater than the expected average and were the only ones that expressed HER-2 and CEA together

[0175] , Patients will be divided into 3 groups and will receive a) 10 million cells; b) 25 million; c) 50 million of SENOVAX™ subcutaneously in the abdominal area once per week for one month and subsequently for 2 additional months, giving a total of 7 injections. Immunological targeting of tumor senescent cells is appealing based on: a) For every tumor senescent cell therapeutically neutralized, approximately 200-300 tumor cells perish, thus reducing ability of tumors to lose expression of antigens; b) The immune system is in direct contact with the tumor senescent cells, while immune access inside tumors is difficult due to areas of necrosis and high interstitial pressure; and c) The elevated expression of Fas Ligand on the tumor senescent cells mediates the selective killing of CD8+ Tumor Infiltrating Lymphocytes (TIL) allowing for a predominance ofFoxP3+ T regulatory cells (Treg) to infiltrate the tumor microenvironment. Thereby demonstrating that the tumor blood vessels act as an immunological barrier promoting tumor tolerance

[0199] , Immune mediated destruction of the tumor endothelium has been shown to significantly increase TILs in mouse models, correlated with induction of antitumor immunity

[0200] , Another further potential benefit of targeting the tumor associated senescent cells is the potential of sensitizing tumors to radiotherapy

[0201] , in part due to the selective thrombotic and apoptotic effects irradiation has on the tumor vasculature [202-205], In one embodiment induction of immunity to senescent cells is performed to sensitize cancer cells to radiation therapy, hormonal therapy, immunotherapy, or chemotherapy. A variety of chemotherapy types may be used in the practice of the invention. Many chemotherapeutic agents are known in the art and include but are not limited to: methotrexate, taxol, mercaptopurine, thioguanine, hydroxyurea, cytarabine, cyclophosphamide, ifosfamide, nitrosoureas, cisplatin, carboplatin, mitomycin, dacarbazine, procarbizine, etoposides, campathecins, bleomycin, doxorubicin, idarubicin, daunorubicin, dactinomycin, plicamycin, mitoxantrone, asparaginase, vinblastine, vincristine, vinorelbine, paclitaxel, and docetaxel, doxorubicin, epirubicin, 5-fluorouracil, taxanes such as docetaxel and paclitaxel, leucovorin, levamisole, irinotecan, estramustine, etoposide, nitrosoureas such as carmustine and lomustine, vinca alkaloids, platinum compounds, mitomycin, gemcitabine, hexamethylmelamine, topotecan, tyrosine kinase inhibitors, tyrphostins, STI-571 or Gleevec.TM. (imatinib mesylate), herbimycin A, genistein, erbstatin, and lavendustin A. taxol, mercaptopurine, thioguanine, hydroxyurea, cytarabine, cyclophosphamide, ifosfamide, nitrosoureas, cisplatin, carboplatin, mitomycin, dacarbazine, procarbizine, etoposides, campathecins, bleomycin, doxorubicin, idarubicin, daunorubicin, dactinomycin, plicamycin, mitoxantrone, asparaginase, vinblastine, vincristine, vinorelbine, paclitaxel, and docetaxel, doxorubicin, epirubicin, 5- fluorouracil, taxanes such as docetaxel and paclitaxel, leucovorin, levamisole, irinotecan, estramustine, etoposide, nitrosoureas such as carmustine and lomustine, vinca alkaloids, platinum compounds, mitomycin, gemcitabine, hexamethylmelamine, topotecan, tyrosine kinase inhibitors, tyrphostinsherbimycin A, genistein, erbstatin, and lavendustin ABCNU, irinotecan, camptothecins, bleomycin, doxorubicin, idarubicin, daunorubicin, dactinomycin, plicamycin, mitoxantrone, asparaginase, vinblastine, vincristine, vinorelbine, paclitaxel, and docetaxel. In a preferred embodiment, the anti-cancer agent can be, but is not limited to, a drug listed: Alkylating agents Nitrogen mustards: Cyclophosphamide Ifosfamide Trofosfamide Chlorambucil Nitrosoureas: Carmustine(BCNU) Lomustine (CCNU) Alkyl sulphonates: Busulfan Treosulfan Triazenes: Dacarbazine Platinum containing Cisplatin compounds: Carboplatin Aroplatin Oxaliplatin Plant Alkaloids Vinca alkaloids: Vincristine Vinblastine Vindesine Vinorelbine Taxoids: Paclitaxel Docetaxel DNA Topoisomerase Inhibitors Epipodophyllins: Etoposide Teniposide Topotecan 9-aminocamptothecin Camptothecin Crisnatol mitomycins: Mitomycin C Anti-metabolites Anti-folates: DHFR inhibitors: Methotrexate Trimetrexate IMP dehydrogenase Mycophenolic acid Inhibitors: Tiazofurin Ribavirin EICAR Ribonuclotide reductase Hydroxyurea Inhibitors: Deferoxamine Pyrimidine analogs: Uracil analogs: 5 -Fluorouracil Floxuridine Doxifluridine Ratitrexed Cytosine analogs: Cytarabine (ara C) Cytosine arabinoside Fludarabine Purine analogs: Mercaptopurine Thioguanine DNA Antimetabolites: 3-HP 2'-deoxy-5-fluorouridine 5-HP alpha-TGDR aphidicolin glycinate ara-C 5-aza-2'-deoxycytidine beta-TGDR cyclocytidine guanazole inosine glycodialdehyde macebecin II pyrazoloimidazole Hormonal therapies: Receptor antagonists: Anti -estrogen: Tamoxifen Raloxifene Megestrol LHRH agonists: Goserelin Leuprolide acetate Anti-androgens: Flutamide Bicalutamide Retinoids / Deltoids Cis-retinoic acid Vitamin A derivative: All-trans retinoic acid (ATRA-IV) Vitamin D3 analogs: EB 1089 CB 1093 KH 1060 Photodynamic therapies: Vertoporfin (BPD-MA) Phthalocyanine Photosensitizer Pc4 Demethoxy- hypocrellin A (2BA-2-DMHA) Cytokines: Interferon-. alpha. Interferon-. gamma. Tumor necrosis factor Angiogenesis Inhibitors: Angiostatin (plasminogen fragment) anti angiogenic antithrombin III Angiozyme ABT-627 Bay 12-9566 Benefin Bevacizumab BMS-275291 cartilage-derived inhibitor (CDI) CAI CD59 complement fragment CEP- 7055 Col 3 Combretastatin A-4 Endostatin (collagen XVIII fragment) Fibronectin fragment Gro-beta Halofuginone Heparinases Heparin hexasaccharide fragment HMV833 Human chorionic gonadotropin (hCG) IM-862 Interferon alpha / beta / gamma Interferon inducible protein (IP- 10) Interleukin- 12 Kringle 5 (plasminogen fragment) Marimastat Metalloproteinase inhibitors (TIMPs) 2-Methoxyestradiol MMI 270 (CGS 27023 A) MoAb IMC-1C11 Neovastat NM-3 Panzem PI-88 Placental ribonuclease inhibitor Plasminogen activator inhibitor Platelet factor-4 (PF4) Prinomastat Prolactin 16 kD fragment Proliferin-related protein (PRP) PTK 787 / ZK 222594 Retinoids Solimastat Squalamine SS 3304 SU 5416 SU6668 SU11248 Tetrahydrocortisol-S tetrathiomolybdate thalidomide Thrombospondin- 1 (TSP-1) TNP-470 Transforming growth factor-beta (TGF-b) Vasculostatin Vasostatin (calreticulin fragment) ZD6126 ZD 6474 famesyl transferase inhibitors (FTI) bisphosphonates Antimitotic agents: allocolchicineHalichondrin B colchicine colchicine derivative dolstatin 10 maytansine rhizoxin thiocolchicine trityl cysteine Others: Isoprenylation inhibitors: Dopaminergic neurotoxins: l-methyl-4-phenylpyridinium ion Cell cycle inhibitors: Staurosporine Actinomycins: Actinomycin D Dactinomycin Bleomycins: Bleomycin A2 Bleomycin B2 Peplomycin Anthracy clines: Daunorubicin Doxorubicin (adriamycin) Idarubicin Epirubicin Pirarubicin Zorubicin Mitoxantrone MDR inhibitors: Verapamil Ca.sup.2+ATPase inhibitors: Thapsigargin.[001099] In other embodiments immunotherapy mediated reduction of senescent cells is performed to increase efficacy of cancer targeting antibodies. Such antibodies may include bagovomab, adecatumumab, afutuzumab, alemtuzumab, altumomab, amatuximab, anatumomab, arcitumomab, bavituximab, bectumomab, bevacizumab, bivatuzumab, blinatumomab, brentuximab, cantuzumab, catumaxomab, cetuximab, citatuzumab, cixutumumab, clivatuzumab, conatumumab, daratumumab, drozitumab, duligotumab, dusigitumab, detumomab, dacetuzumab, dalotuzumab, ecromeximab, elotuzumab, ensituximab, ertumaxomab, etaracizumab, farietuzumab, ficlatuzumab, figitumumab, flanvotumab, futuximab, ganitumab, gemtuzumab, girentuximab, glembatumumab, ibritumomab, igovomab, imgatuzumab, indatuximab, inotuzumab, intetumumab, ipilimumab, iratumumab, labetuzumab, lexatumumab, lintuzumab, lorvotuzumab, lucatumumab, mapatumumab, matuzumab, milatuzumab, minretumomab, mitumomab, moxetumomab, narnatumab, naptumomab, necitumumab, nimotuzumab, nofetumomabn, ocaratuzumab, ofatumumab, olaratumab, onartuzumab, oportuzumab, oregovomab, panitumumab, parsatuzumab, patritumab, pemtumomab, pertuzumab, pintumomab, pritumumab, racotumomab, radretumab, rilotumumab, rituximab, robatumumab, satumomab, sibrotuzumab, siltuximab, simtuzumab, solitomab, tacatuzumab, taplitumomab, tenatumomab, teprotumumab, tigatuzumab, tocilizumab, tositumomab, trastuzumab, tucotuzumab, ublituximab, veltuzumab, vorsetuzumab, votumumab, zalutumumab, CC49 and 3F8. The exemplified therapeutic antibodies may be further labeled or combined with a radioisotope particle, such as indium In 111, yttrium Y 90, iodine 1-131.[001100] In one embodiment, dendritic cells are the APC desired and dendritic cells are endogenous. In other embodiments, dendritic cells are generated ex vivo and administered in vivo. A discussion of dendritic cells is provided to assist one of skill inthe art in practicing the invention. Dendritic cells (DC) possess unique morphology similar to neuronal dendrites and were originally identified based on their ability to stimulate the adaptive immune system. Of importance to the field of tumor immunotherapy, dendritic cells appear to be the only cell in the body capable of activating naive T cells

[0035] , The concept of dendritic cells instructing naive T cells to differentiate into effector or memory cells is fundamental because it places the dendritic cell as the most powerful antigen presenting cell. This implies that for immunotherapeutic purposes dendritic cells do not necessarily need to be administered at high numbers in patients. One way in which dendritic cells have been described is as sentinels of the immune system that are patrolling the body in an immature state [36, 37], Once DC are activated, by a stimulatory signal such as a Damage Associated Molecular Patterns (DAMPS) the DC then migrate into the draining lymph nodes through the afferent lymphatics. During the trafficking process, DC degrade ingested proteins into peptides that bind to both MHC class I molecules and MHC class II molecules. This allows the DC to: a) perform cross presentation in that they ingest exogenous antigens but present peptides in the MHC I pathway; and b) activate both CD8 (via MHC I) and CD4 (via MHC II). Interestingly, lipid antigens are processed via different pathways and are loaded onto non-classical MHC molecules of the CD1 family

[0038] ,[001101] The possibility of utilizing DC to stimulate immunity was made into reality in animal studies that took advantage of the ability of immature DC to potently phagocytose various antigens. If the antigens possessed DAMPs, or if DAMPs were present in the environment, the DC would mature and present the antigens, resulting in stimulation of potent T cell immunity. Accordingly, in the initial studies, immature DC were incubated with various antigens, subsequent to which a maturation signal (replicating natural DAMPs) was applied and the DC were injected into animals. Thus, DC were utilized as a type of “cellular adjuvant”. Indeed, it was discovered that the classical adjuvants such as Fruend’s Adjuvant contained a high concentration of DAMPs, which resulted in the stimulation of local DC at vaccination site in vivo.[001102] One of the first clinical applications of DC was prostate cancer. In an early reported, thirty three androgen resistant metastatic prostate cancer patients were treated with DC that were pulsed with peptides from a prostate specific antigen termed PMSA. Nine partial responders were identified based on NCPC criterial, plus 50% reduction ofPSA. Four of the partial responders were also responders in the phase I study, with an average response duration of 225 days. Their combined average total response period was over 370 days. Five other responders in the secondary immunizations at the Phase II were non-responders in the phase I study. Their average partial response period was 196 days. These data support the safety of follow-up infusion of DC that have been pulsed with tumor antigen derived peptide

[0046] ,[001103] The same group published a subsequent paper on an additional 33 patients that had not received prior DC immunization in the Phase I. All subjects received six infusions of DC pulsed with PSM-P1 and -P2 at six week intervals without any treatment associated adverse events. Six partial and two complete responders were identified in the phase II study based on NPCP criteria, plus 50% reduction of prostate-specific antigen (PSA), or resolution in previously measurable lesions on ProstaScint scan

[0047] , The same group analyzed immune response in patients who had clinical remission or relapsed. A strong correlation was found between delayed type hypersensitivity response to the PSM- P1 and PSM-P2 and clinical response

[0048] ,[001104] Another subsequent study utilized DC generated using GM-CSF and IL-4 but pulsed with PAP, another prostate antigen. Specifically, the PAP was delivered to the DC by means of generation of a PAP-GM-CSF fusion protein. Two intravenous infusions of the generated cells were performed one month apart in 12 patients with androgen resistant prostate cancer. The infusions were followed by three s.c. monthly doses of the fusion protein without cells. Treatment was well tolerated and circulating prostatespecific antigen levels dropped in three patients. Immune response to the fusion protein was observed, as well as to PAP

[0049] ,[001105] One example of generating dendritic cells useful for the invention involves obtaining leukocytes of patients by leukapheresis. Numerous means of leukapheresis are known in the art. In one example, a Fresenius Device (Fresenius Com. Tec) is utilized with the use of the MNC program, at approximately 1500 rpm, and with a Pl Y kit. The plasma pump flow rates are adjusted to approximately 50 mL / min. Various anticoagulants may be used, for example ACD-A. The Inlet / ACD Ratio may be ranged from approximately 10: 1 to 16: 1. In one embodiment approximately 150 mL of blood is processed. The leukapheresis product is subsequently used for initiation of dendritic cell culture. Mononuclear cells are isolated by the Ficoll-Hypaque density gradientcentrifugation. Monocytes are then enriched by the Percoll hyperosmotic density gradient centrifugation followed by two hours of adherence to the plate culture. Cells are then centrifuged at 500 g to separate the different cell populations. Adherent monocytes are cultured for 7 days in 6-well plates at 2 * 106 cells / mL RMPI medium with 1% penicillin / streptomycin, 2 mM L-glutamine, 10% of autologous, 50 ng / mL GM-CSF and 30 ng / mL IL-4. On day 7, the immature DCs are then induced to differentiate into mature DCs by culturing for 48 hours with 30 ng / mL interferon gamma (IFN-y). During the course of generating DC for clinical purposes, microbiologic monitoring tests are performed at the beginning of the culture, on the fifth day and at the time of cell delivery.[001106] In some embodiments, DC are kept immature and pulsed with tumor endothelial antigens prior to administration in a patient for stimulation of immunity to said tumor endothelial antigens, method for differentiating and maintaining immature dendritic cells ex vivo or in vitro in a state optimized for the uptake, processing and presentation of a selected antigen. The method comprises providing a cell population comprising non-activated monocytic dendritic cell precursors i.e., monocytes that express the GM-CSF receptor on their surface, and other such dendritic cell precursors, and contacting the non-activated dendritic cell precursors with a dendritic cell culture media supplemented with granulocyte-macrophage colony stimulating factor in the absence of additional cytokines. Contrary to prior methods the additional cytokines are not required for the generation of dendritic cells from isolated non-activated monocytic dendritic cell precursors.[001107] Activation of the monocytic dendritic precursor cells can be prevented by, for example, inhibiting or blocking the adhesion of the precursor cells to a solid surface the cells would contact during a typical isolation and / or enrichment process or during cell culture. The solid surface can be a culture vessel, such as a cell culture flask, bottle or bag, used to obtain or maintain the cells ex vivo or in vitro. The solid surface can also be any surface of a vessel or device used in the preparation of cell population enriched for the dendritic cell precursors, e.g., a filter surface; a bead used in purification, such as a magnetic, glass or plastic bead; tubing, culture vessel, and the like. Inhibition of the adhesion of the non-activated monocytic dendritic cell precursors can be by the addition of a high concentration of an animal or human protein to the cell culture or isolation medium. A high concentration of animal or human protein as used herein comprises about1 to about 10% w / v of the protein. The animal protein can comprise an albumin, serum, plasma, gelatin, poly-amino acid, and the like, as long as they do not themselves activate the cells. Activation of the monocytic dendritic precursor cells can also be blocked or inhibited by the addition of a metal chelator to the cell culture and / or isolation medium. The metal chelator can comprise EDTA, EGTA, and the like. The addition of these dendritic cell agents is believed to minimize the activation of the precursor cells by reducing the concentration of divalent cationic metals in the culture media. The activation of the monocytic dendritic precursor cells can also be prevented or inhibited by isolation or enrichment and culturing of the dendritic precursor cells in a low cellular avidity culture vessel. The low cellular avidity culture vessels typically comprise materials such as polypropylene, Teflon.RTM., PFTE, and the like. As with adding the animal or human protein reducing or blocking adhesion of the dendritic precursor cell to the solid surface prevents activation of the cells and allows for the differentiation and maintenance of the cells into immature dendritic cells in the presence of dendritic cell culture media supplemented with GM-CSF without any additional cytokines. Performing the isolation of the precursor cells at temperatures below about 37. degree. C., such as room temperature, further reduces the proportion of monocytic dendritic precursor cells that undergo activation in the cell population. The methods of the present invention can comprise the combination of any or all of these agents, materials, and / or conditions. In one particular embodiment of the invention the dendritic cell culture medium is serum free and an animal protein, such as serum albumin, is added to decrease the avidity of the dendritic cell precursors for the surface of the culture vessel to prevent and / or reduce activation of the monocytic dendritic precursor cells.[001108] Typically, the cell populations that comprise monocytic dendritic precursor cells are obtained from peripheral blood, a leukapheresis product, an apheresis product, cord blood, spleen, lymph node, thymus, or bone marrow. The cell populations can be cryopreserved prior to and subsequent to practice of the methods of the present invention. Further, the cell population can be further enriched for monocytic precursor cells by tangential flow filtration, antibody panning, differential centrifugation, and the like. When the cell population is further enriched by tangential flow filtration the filter typically comprises a 5.5 micron pore, the recirculation rate is about 1400 ml / min, the filtration rate is approximately 15 to about 21 ml / min, typically 17 ml / min, and the filtration time is about 60 to about 90 min.[001109] Immature dendritic cells that have been obtained by the methods of the present invention can be contacted with a selected antigen of interest for a sufficient time for uptake and processing of the antigen. Once processed the antigen is presented on the surface of the dendritic cells. Further, the immature dendritic cells can be contacted with a dendritic cell maturation agent either prior to, simultaneously with, or subsequent to contact with the antigen of interest. The dendritic cell maturation agent can comprise Bacillus Calmette-Guerin (BCG), lipopolysaccharide (LPS), tumor necrosis factor .alpha. (TNF-alpha.), interferon gamma (IFN-gamma.), or combinations thereof. In certain embodiments, the dendritic cell maturation agent is a combination of inactivated BCG and IFN-gamma. Selected antigens useful in the methods of the present invention include, but are not limited to a tumor specific antigen, a tumor associated antigen, a viral antigen, a bacterial antigen, tumor cells, nucleic acid obtained from tumor cells, bacterial cells, viral particles, recombinant cells expressing an antigen, a cell lysate, a membrane preparation, a recombinantly produced antigen, a peptide derived from the antigen of interest, or an isolated antigen of interest. At any stage, including subsequent to contact with the selected antigen, uptake, processing and maturation of the dendritic cells, the cells can be cryopreserved for later use.[001110] In one embodiment of the present invention the non-activated monocytic dendritic cell precursors are prepared by preventing the tight adherence of the population of cells comprising the monocytic dendritic cell precursors to a cell culture vessel. Tight adherence can be prevented by, for example, adding a blocking agent to the culture media used to maintain the dendritic cell precursors in vitro or ex vivo. Such blocking agents can include high concentrations of protein, including for example and not as a limitation, an animal or human protein, such as albumins, serum, plasma, gelatin, poly-amino acids, and the like. In particular, albumins from bovine or human sources are typically used. Typically, a concentration of about 1% to about 10% w / v blocking agent is used. In particular, human serum albumin (HSA) can be used at a concentration of about 1%, 2% or up to about 5% or more. It should be noted that blocking agents must be selected that do not themselves activate the cells. The culture media can be any media typically used for the culture of monocytic dendritic cell precursors including those that do not require serum.[001111] In another embodiment of the invention, a metal chelator can be added to the culture media to further prevent or reduce the activation of the monocytic dendritic cells by chelating divalent cations, including for example, but not limitation, calcium ions. The use of low adherence or low-binding culture vessels can also reduce the avidity of attachment or binding of the dendritic cell precursors to prevent the cells from being activated. Particularly preferred low binding materials include, for example, but are not limited to, polypropylene, Teflon.RTM., PFTE, and the like. The metal chelator can be used in combination with the blocking agents described above. Monocytic dendritic cell precursors and immature dendritic cells can also be prepared in a closed, aseptic system. As used herein, the terms "closed, aseptic system" or "closed system" refer to a system in which exposure to non-sterile, ambient, or circulating air or other non-sterile conditions is minimized or eliminated. Closed systems for isolating dendritic cell precursors and immature dendritic cells generally exclude density gradient centrifugation in open top tubes, open air transfer of cells, culture of cells in tissue culture plates or unsealed flasks, and the like. In a typical embodiment, the closed system allows aseptic transfer of the dendritic cell precursors and immature dendritic cells from an initial collection vessel to a sealable tissue culture vessel without exposure to non-sterile air.[001112] In certain embodiments, non-activated monocytic dendritic cell precursors are isolated by partial adherence to a monocyte-binding substrate. For example, a population of leukocytes (e.g., isolated by leukapheresis) can be contacted with a monocytic dendritic cell precursor adhering substrate, e.g., a glass coated microcarrier bead, in the presence of a blocking agent that prevents non-specific binding as well as reduces the binding avidity of the monocytic dendritic cell precursor cells. When the population of leukocytes is contacted with the substrate, the monocytic dendritic cell precursors in the leukocyte population preferentially loosely adhere to the substrate. Other leukocytes (including other potential dendritic cell precursors) e.g., proliferating dendritic cell precursors, and the like exhibit reduced binding affinity to the substrate, thereby allowing a subset of the monocytic dendritic cell precursors to be preferentially enriched on the surface of the substrate. Loose adhesion does not activate the monocytic dendritic cell precursors. Subsequent to cell binding and elution of non-adherent cells, the subset of monocytic dendritic cell precursors are eluted from the substrate by a buffered salt solution that can be supplemented with a non-toxic chelating agent. By "non-toxic chelating agent" is intended those chelating agents that do not substantially reduce theviability of the monocytic dendritic cell precursors, for example but not limitation, EDTA, EGTA, and the like.[001113] Suitable substrates include, for example, those having a large surface area to volume ratio, such as glass beads or a glass coated microcarrier. Such substrates can be, for example, a particulate or fibrous substrate. Suitable particulate substrates include, for example, glass particles, glass-coated plastic particles, glass-coated polystyrene particles, and other beads suitable for protein absorption. Suitable fibrous substrates include glass or glass coated microcapillary tubes and microvillous membrane. The particulate or fibrous substrate usually allows the adhered monocytic dendritic cell precursors to be eluted without substantially reducing the viability of the adhered cells. A particulate or fibrous substrate can be substantially non-porous to facilitate elution of monocytic dendritic cell precursors or dendritic cells from the substrate. A "substantially non- porous" substrate is a substrate in which at least a majority of pores present in the substrate are smaller than the cells to minimize entrapping cells in the substrate.[001114] Adherence of the monocytic dendritic cell precursors to the substrate without activation can optionally be modulated by the addition of binding media. Suitable binding media include monocytic dendritic cell precursor culture media (e.g., AIM-V.RTM., RPMI 1640, DMEM, X-VIVO 15.RTM., and the like) supplemented, individually or in any combination, with for example, cytokines (e.g., Granulocyte / Macrophage Colony Stimulating Factor (GM-CSF), blood plasma, serum (e.g., human serum, such as autologous or allogeneic sera), purified proteins, such as serum albumin, divalent cations (e.g., calcium and / or magnesium ions) and other molecules that aid in the specific adherence of monocytic dendritic cell precursors to the substrate, or that prevent adherence of non-monocytic dendritic cell precursors to the substrate. In certain embodiments, the blood plasma or serum can be heat-inactivated. The heat-inactivated plasma can be autologous or heterologous to the leukocytes.[001115] In another method for enriching a cell population for monocytic dendritic cell precursors from a sample of blood constituents provides for tangential flow filtration of the leukocytes from cellular debris, red blood cells and other cells and particles in a blood sample. The method comprises the following steps: (a) introducing the blood sample into a tangential flow filtration (TFF) unit, the TFF unit comprising a cross-flow chamber, a filtrate chamber, and a filter in fluid communication with the cross-flowchamber and the filtrate chamber, the filter having a pore size of about 1 to about 10 microns, typically about 5.5 microns; (b) recirculation of the sample through the TFF unit at a predetermined input rate, typically about 1400 ml / min, and a predetermined filtration rate, typically about 15 to about 21 ml / min, more typically about 17 ml / min, the predetermined input rate at least five times the predetermined filtration rate; wherein the predetermined filtration rate is less than the unopposed filtration rate for the filter; and (c) isolating a cell population enriched for leukocytes. Typically, the filtration time is about 60 to about 90 minutes. The method can result in an enriched cell population that is substantially free of non-leukocyte blood constituents including plasma, platelets and erythrocytes. The enriched cell population produced by this method can comprise at least about 50% monocytic dendritic cell precursors and preferentially at least about 70% monocytic dendritic cell precursors that have not been activated. The method can further comprise the collecting of blood from a subject and preparing the sample from the blood by leukapheresis, density centrifugation, differential lysis, filtration, or preparation of a buffy coat prior to tangential flow filtration. Performing the TFF purification of the monocytic DC precursors at room temperature, or below (further aids in reducing the activation of the cells.[001116] Cell populations enriched for non-activated monocytic dendritic cell precursors are cultured ex vivo or in vitro for differentiation, maturation and / or expansion. (As used herein, isolated immature dendritic cells, dendritic cell precursors, T cells, and other cells, refers to cells that, by human hand, exist apart from their native environment, and are therefore not a product of nature. Isolated cells can exist in purified form, in semi-purified form, or in a non-native environment.) Briefly, ex vivo differentiation typically involves culturing the non-activated dendritic cell precursors, or populations of cell comprising non-activated dendritic cell precursors, in the presence of one or more differentiation agents. In particular, the differentiation agent in the present invention is granulocyte-macrophage colony stimulating factor (GM-CSF) used alone without other added cytokines, particularly without the use of Interleukin 4 (IL-4). In certain embodiments, the non-activated monocytic dendritic cell precursors are differentiated to form monocyte-derived immature dendritic cells capable of inducing the activation and proliferation of a substantial number of T cells in a population of peripheral blood mononuclear cells.[001117] The dendritic cell precursors can be differentiated and maintained as immature dendritic cell precursors in suitable culture conditions. Suitable tissue culture media include AIM-V.RTM., RPMI 1640, DMEM, X-VIVO 15.RTM., and the like supplemented with GM-CSF. The tissue culture media can be supplemented with serum, amino acids, vitamins, divalent cations, and the like, to promote differentiation of the cells into dendritic cells. In certain embodiments, the dendritic cell precursors can be cultured in a serum-free media. Such culture conditions can optionally exclude any animal-derived products. Typically, GM-CSF is added to the culture medium at a concentration of about 100 to about 1000 units / ml, or typically 500 units / ml of GM-CSF. Dendritic cell precursors, when differentiated to form immature dendritic cells demonstrate a typical expression pattern of cell surface proteins seen for immature monocytic dendritic cells, e.g., the cells are typically CD14.sup.- and CD1 lc.sup.+, CD83.sup.- and express low levels of CD86. In addition, the immature dendritic cells are able to capture soluble antigens via specialized uptake mechanisms.[001118] The immature dendritic cells can be matured to form mature dendritic cells. Mature DCs lose the ability to take up antigen and the cells display up-regulated expression of co-stimulatory cell surface molecules and secrete various cytokines. Specifically, mature DCs express higher levels of MHC class I and II antigens and are generally identified as CD80.sup.+, CD83.sup.+, and CD86.sup.+. Greater MHC expression leads to an increase in antigen density on the DC surface, while up regulation of co-stimulatory molecules CD80 and CD86 strengthens the T cell activation signal through the counterparts of the co-stimulatory molecules, such as CD28 on the T cells.[001119] Mature dendritic cells can be prepared (i.e., matured) by contacting the immature dendritic cells that have been cultured in the presence of GM-CSF alone with effective amounts or concentrations of a dendritic cell maturation agent. Dendritic cell maturation agents can include, for example, BCG, IFN-gamma., LPS, TNF-alpha, and the like. Effective amounts of BCG typically range from about 10. sup.5 to 10. sup.7 cfu per milliliter of tissue culture media. Effective amounts of IFN-gamma. typically range from about 100-1000 U per milliliter of tissue culture media. Bacillus Calmette-Guerin (BCG) is an avirulent strain of M. bovis. As used herein, BCG refers to whole BCG as well as cell wall constituents, BCG-derived lipoarabidomannans, and other BCG components thatare associated with induction of a type 2 immune response. BCG is optionally inactivated, such as heat-inactivated BCG, formalin-treated BCG, and the like.[001120] The immature DCs are typically contacted with effective amounts of BCG and IFN-gamma. for about one hour to about 48 hours. The immature dendritic cells can be cultured and matured in suitable maturation culture conditions. Suitable tissue culture media include AIM-V.RTM., RPMI 1640, DMEM, X-VIVO 15.RTM., and the like. The tissue culture media can be supplemented with amino acids, vitamins, cytokines, such as GM-CSF, divalent cations, and the like, to promote maturation of the cells. Typically, about 500 units / ml of GM-CSF is used.[001121] Maturation of dendritic cells can be monitored by methods known in the art for dendritic cells. Cell surface markers can be detected in assays familiar to the art, such as flow cytometry, immunohistochemistry, and the like. The cells can also be monitored for cytokine production (e.g., by ELISA, another immune assay, or by use of an oligonucleotide array). Mature DCs of the present invention also lose the ability to uptake antigen, which can be analyzed by uptake assays familiar to one of ordinary skill in the art.[001122] Means of generating dendritic cells for clinical use are known in the art and described in the following references for specific tumor types melanoma [59-110], soft tissue sarcoma

[0111] , thyroid [112-114], glioma [115-136], multiple myeloma ,[137-145], lymphoma [146-148], leukemia [149-156], as well as liver [157-162], lung [163-176], ovarian [177-180], and pancreatic cancer [181-183], The present disclosure also provides a method of enhancing antigen presenting cell activation and / or availability in a patient in need of a T cell therapy comprising administering to the patient a dose of cyclophosphamide between 200 mg / m.sup.2 / day and 2000 mg / m.sup.2 / day and a dose of fludarabine between 20 mg / m.sup.2 / day and 900 mg / m.sup.2 / day.[001123] In some embodiments, specific antigens are immunized following polyvalent immunization, said specific antigens administered in the form of DNA vaccines.Numerous publications have reported animal and clinical efficacy of DNA vaccines which are incorporated by reference [206-208], In addition to direct DNA injection techniques, DNA vaccines can be administered by electroporation

[0209] , The nucleic acid compositions, including the DNA vaccine compositions, may further comprise apharmaceutically acceptable excipient. Examples of suitable pharmaceutically acceptable excipients for nucleic acid compositions, including DNA vaccine compositions, are well known to those skilled in the art and include sugars, etc. Such excipients may be aqueous or non-aqueous solutions, suspensions, and emulsions. Examples of non-aqueous excipients include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate. Examples of aqueous excipient include water, alcoholic / aqueous solutions, emulsions or suspensions, including saline and buffered media. Suitable excipients also include agents that assist in cellular uptake of the polynucleotide molecule. Examples of such agents are (i) chemicals that modify cellular permeability, such as bupivacaine, (ii) liposomes or viral particles for encapsulation of the polynucleotide, or (iii) cationic lipids or silica, gold, or tungsten microparticles which associate themselves with the polynucleotides. Anionic and neutral liposomes are well- known in the art (see, e.g., Liposomes: A Practical Approach, RPC New Ed, IRL press (1990), for a detailed description of methods for making liposomes) and are useful for delivering a large range of products, including polynucleotides. Cationic lipids are also known in the art and are commonly used for gene delivery. Such lipids include Lipofectin.TM. also known as DOTMA (N— [I-(2,3-dioleyloxy) propyls N,N, N- trimethylammonium chloride), DOTAP (1,2-bis (oleyloxy)-3 (trimethylammonio) propane), DDAB (dimethyldioctadecyl-ammonium bromide), DOGS (dioctadecylamidologlycyl spermine) and cholesterol derivatives such as DCChol (3 beta- (N— (N',N'-dimethyl aminomethane)-carbamoyl) cholesterol). A particular useful cationic lipid formulation that may be used with the nucleic vaccine provided by the disclosure is VAXFECTIN, which is a commixture of a cationic lipid (GAP-DMORIE) and a neutral phospholipid (DPyPE) which, when combined in an aqueous vehicle, self-assemble to form liposomes. Cationic lipids for gene delivery are preferably used in association with a neutral lipid such as DOPE (dioleyl phosphatidylethanolamine). In addition, a DNA vaccine can also be formulated with a nonionic block copolymer such as CRL1005. Other immunization means include prime boost regiments. The polypeptide and nucleic acid compositions can be administered to an animal, including human, by a number of methods known in the art. Examples of suitable methods include: (1) intramuscular, intradermal, intraepidermal, intravenous, intraarterial, subcutaneous, or intraperitoneal administration, (2) oral administration, and (3) topical application (such as ocular, intranasal, and intravaginal application). One method of intradermal or intraepidermal administration of a nucleic acid vaccine composition that may be used is gene gundelivery using the Particle Mediated Epidermal Delivery (PMED.TM.) vaccine delivery device marketed by PowderMed. PMED is a needle-free method of administering vaccines to animals or humans. The PMED system involves the precipitation of DNA onto microscopic gold particles that are then propelled by helium gas into the epidermis. The DNA-coated gold particles are delivered to the APCs and keratinocytes of the epidermis, and once inside the nuclei of these cells, the DNA elutes off the gold and becomes transcriptionally active, producing encoded protein. This protein is then presented by the APCs to the lymphocytes to induce a T-cell-mediated immune response. Another method for intramuscular administration of a nucleic acid vaccine provided by the present disclosure is electroporation. Electroporation uses controlled electrical pulses to create temporary pores in the cell membrane, which facilitates cellular uptake of the nucleic acid vaccine injected into the muscle. Where a CpG is used in combination with a nucleic acid vaccine, it is preferred that the CpG and nucleic acid vaccine are coformulated in one formulation and the formulation is administered intramuscularly by electroporation. A helper T cell and cytotoxic T cell stimulatory polypeptide can be introduced into a mammalian host, including humans, linked to its own carrier or as a homopolymer or heteropolymer of active polypeptide units. Such a polymer can elicit increase immunological reaction and, where different polypeptides are used to make up the polymer, the additional ability to induce antibodies and / or T cells that react with different antigenic determinants of the tumor. Useful carriers known in the art include, for example, thyroglobulin, albumins such as human serum albumin, tetanus toxoid, polyamino acids such as poly(D-lysine:D-glutamic acid), influenza polypeptide, and the like. Adjuvants such as incomplete Freunds adjuvant, GM-CSF, aluminum phosphate, CpG containing DNA, inulin, Poly (IC), aluminum hydroxide, alum, or montanide can also be used in the administration of a helper T cell and cytotoxic T cell stimulatory polypeptide.[001124] Subsequent to augmentation of lymphocyte numbers specific for killing of the tumor, modification of the tumor microenvironment may be performed. In one embodiment, macrophage modulators are used. Macrophages may comprise distinct subpopulations, known as classical Ml and alternative M2. Ml macrophages are described as the pro-inflammatory sub-type of macrophages induced by IFN-gamma. and LPS. They produce effector molecules (e.g., reactive oxygen species) and pro-inflammatory cytokines (e.g., IL-12, TNF-alpha. and IL-6) and they trigger Thl polarized responses.Under certain contexts, tumors manipulate macrophages to take on the M2 phenotype, and this subsequently leads to enhanced tumor progressing factors. In certain embodiments, the cell-based vaccine of the invention is administered to a subject to achieve manipulation of macrophages. In one embodiment, the methods of the invention are applied to shift macrophages from an M2 phenotype to an Ml phenotype. In certain embodiments, the compositions and methods of the invention are applied to treat a subject with cancer, wherein an M2 phenotype of macrophages is identified in the subject. In certain embodiments, biomarkers of a switch to an M2 phenotype are identified in a subject prior to and following administration of a cell-based vaccine of the invention. In certain embodiments, the levels of expression of the cytokines IL-4 and IL-10 are measured in plasma or serum of the subject prior to and following administration of a composition of the invention. In one embodiment, administration of a composition of the invention induces a reduced expression of IL-4 and / or IL- 10 in peripheral blood. In another embodiment, the Fc gamma receptor IIB is measured on peripheral blood cells of the subject. In one embodiment, administration of a composition of the invention induces a reduced expression of Fc gamma receptor IIB on peripheral blood cells.EXAMPLES[001125] The following examples are not intended as limitations. Rather they demonstrate illustrative embodiments of the present invention.Example 1: Generation of a Dendritic Cell (DC) Vaccine Targeting Senescent Cells Comprising Dendritic Cells Pulsed with Lysate from Senescent Fibroblasts[001126] An autologous DC vaccine was generated using two tissue sources from a subject; 1) Autologous peripheral blood mononuclear cells (PBMC) for generating DC; 2) Autologous dermal fibroblasts as a source of senescence-related antigens, which were used to pulse the DC. The autologous DC vaccine pulsed with lysate from dermal fibroblasts was then utilized as a cancer vaccine to generate an immune response against senescent cells in the subject.[001127] Generation of the antigenic source: Dermal fibroblasts were obtained from a punch biopsy obtained from skin of the subject. These dermal fibroblasts were used as the source of antigen for pulsing DC. The following steps were performed to obtain a lysate, the antigenic source, from dermal fibroblasts:a) Culture of Fibroblasts. Human dermal fibroblasts isolated from skin biopsies of a subject were obtained from ATCC. The human dermal fibroblasts were cultured in DMEM / Ham’s F-12 (1 :1) (D6421; Sigma) under 5% C02 and 37 °C with 10% fetal calf serum (F7524; Sigma) and 4 mM L-glutamine (G7513; Sigma). By incubating cells at 37 °C for 5 min with 0.1% trypsin and 0.02% EDTA, cells were detached and split 1 :2. Cells were counted using an automated cell counter (Beckman Coulter) Vi-CELL XR. (All experiments were performed with one donor in three independent replicates). b) Senescence induction with doxorubicin. Fibroblasts were seeded at 3500 cells / cm2. Cells were cultured in doxorubicin one day and the second dose 4 days after seeding, during this period from seeding to assessment, for quiescent cells media was changed regularly and for proliferating cells, 1 :2 splitting was performed twice a week. Concentrations of doxorubicin used were between 10 nM and 200 nM to evaluate the efficacy of senescence induction at various time points in culture. c) Beta-Galactosidase (P-Gal) Staining. Cells were washed in PBS, fixed for 3 minutes (at room temperature) in 2% formaldehyde / 0.2% glutaraldehyde (or3%formaldehyde), washed, and incubated at 37°C (no C02) with fresh senescence-associated (3-Gal(SA-,3-Gal) stain solution : 1 mg of 5-bromo-4- chloro-3-indolylP3-D-galactoside(X-Gal)perml stock = 20 mg of dimethylformamideperi) / 40mM citric acid / sodium phosphate, pH6.0 / 5mMpotassiumferrocyanide / 5mMpotassium ferricyanide / 150mM NaCl / 2mMMgC12. Staining was evident in 2-4 hr and maximal in 12-16 hr. To detect lysosomal, P-Gal, the citric acid / sodium phosphate was pH 4.0. FIG. 1 depicts P- Gal staining following doxorubicin exposure at various concentrations and for various durations in culture. The data show optimal induction of P-Gal , indicative of senescence, at concentrations of doxorubicin of 100 nM, as well as robust expression of P-Gal at 200 nM. In some subsequent experiments, 150 nM doxorubicin was selected for senescence induction based on P-Gal expression levels obtained at this concentration. d) p!6 and High Mobility Group Box 1 (HMGB1) quantification. To evaluate the senescent phenotype of fibroblasts exposed to doxorubicin, cells were digested with trypsin and total protein was extracted from cells using RIPA lysis buffer. The protein concentration was measured with a bicinchoninic acid protein (BCA)assay kit (Beyotime Institute of Biotechnology). Total protein was adjusted to a concentration of 1 mg / ml and 10 pl protein / lane was separated via SDS-PAGE on 12% gel for 90 min, then transferred to PVDF membranes for 90 min. The membranes were subsequently blocked with 5% skimmed milk for 2 h at room temperature, and after washing thrice with Tris-buffered saline Tween-20 (0.1%, TBST), the membranes were incubated anti -pl 6 (Abeam) anti-GAPDH (Santa Cruz Biotechnology, Inc.). Following incubation with the primary antibody, the membranes were washed thrice with TBST and incubated with horseradish peroxidase-conjugated anti -mouse IgG (1 :2,000; Cell Signaling Technology, Inc.) or anti-rabbit IgG (1 :2,000; Cell Signaling Technology, Inc.) secondary antibodies for 1 h at room temperature. Protein bands were visualized using a FluorChem E system (Hot Technology Co., Ltd.) after the membranes were washed thrice with TBST. The protein bands were visualized by luminescent reagents (Santa Cruz Biotechnology, Inc.) and analyzed using Imaged software (version 1.43; National Institutes of Health). FIG. 2 and FIG. 3 show that pl6 and HMGB, respectively, are induced by treatment of fibroblasts with doxorubicin, and that expression of these molecules was detected at 100 nM (maximal), and at 200 nM of doxorubicin.[001128] Generation of DCs: Blood was drawn from the subject as a source of PBMC that were subsequently used to generate DCs for the vaccine. The following steps were performed: a) Blood mononuclear cells were prepared using the buffy coat method by Ficoll- Paque density gradient. The total number of viable mononuclear cells were determined by trypan blue exclusion. Cell concentrations of 1-2 x 107 cells / ml were prepared in complete RPMI medium. b) The interface cells were transferred to a 50-ml conical centrifuge tube using a Pasteur pipet. The density gradient medium was diluted four-fold with RPMI 1640 and centrifuged for 10 min at 450 x g, room temperature. The supernatant fluid was removed, and the cells were resuspended in cell culture medium. The wash was repeated, and the cell concentration was adjusted to 1 x 107 cells / ml. c) The resuspended cells were subjected to T cell depletion by magnetic bead- mediated T cell depletion (MACS, Miltenyi Biotec).d) The T cell-depleted mononuclear cell suspension was plated into 100-mm tissue culture plates using 10 ml of the cell suspension per plate. The plates were incubated overnight at 37°C to allow monocytes to adhere to the plastic. e) Cells were cultured for 2, 4, 6 days in AIM-V medium in presence of 800 U / ml recombinant human GM-CSF (rhGM-CSF) and 50 ng / ml IL-4. f) After the culture period, the expression of costimulatory molecules (CD40, CD80; and CD86) was quantified by flow cytometry to identify DC and assess their level of maturity. Expression of these molecules was quantified by flow cytometry. FIG. 4, FIG. 5, and FIG. 6 show that the DC generated using this protocol express the costimulatory molecules CD40, CD80, and CD86, respectively. These data provide support that these cells have a DC phenotype. g) Additionally, allogeneic mixed lymphocyte reaction (MLR) was performed to evaluate the ability of the DC as stimulator cells to induce T cell proliferation. The experiment was performed by culturing varying concentrations of DC with the allogeneic responder cells (25k, 50k and 100k DC to 100k allogeneic lymphocytes per well in the MLR assay). FIG. 7 depicts the ability of the DC to stimulate proliferation in the MLR assay. These data support the use of these DC as a cellular vaccine that is administered to stimulate an immune response in a subject.[001129] Generation of a Cellular Vaccine using DCs and Fibroblast Lysate: Autologous DCs and fibroblasts cultivated using the above-mentioned methods were used to generate a vaccine against senescent cells. DCs were fed varying doses of lysate prepared from senescent fibroblasts, were subsequently washed, and evaluated as follows: a) Viability of the cells after feeding using trypan blue and enumeration of the cells. FIG. 8 shows that uptake of fibroblast lysate does not affect DC viability. b) Expression of pl 6, beta-galactosidase (P-Gal), and HMGB1 after pulsing with fibroblast lysate. FIG. 9 depicts pl6 expression in DC, determined by intracellular staining and flow cytometry. The data demonstrate that the senescence-related antigen is taken up by these cells using the protocol disclosed herein.[001130] FIG. 1 : Optimization of senescence induction in fibroblasts by exposure to 3 different doxorubicin concentrations (beta-galactosidase measurement).[001131] FIG. 2: Optimization of senescence induction in fibroblasts by exposure to three concentrations of doxorubicin (pl 6 measurement).[001132] FIG. 3 : Optimization of senescence induction in fibroblasts by exposure to three different concentrations of doxorubicin (HMGB1 measurement).[001133] FIG. 4: Measurement of CD40 Expression on Dendritic Cells Generated for an Autologous Vaccine using GM-CSF, IL-4, or a combination.[001134] FIG. 5: Measurement of CD80 Expression on Dendritic Cells Generated for an Autologous Vaccine using GM-CSF, IL-4, or a combination.[001135] FIG. 6: Measurement of CD86 Expression on Dendritic Cells Generated for an Autologous Vaccine using GM-CSF, IL-4, or a combination.[001136] FIG. 7: Measurement of allostimulatory activity of dendritic cells in Mixed Lymphocyte Reactions using dendritic cells that had been generated using GM-CSF, IL- 4, or a combination, or control cultures (no cytokines).[001137] FIG. 8: Viability of dendritic cells pulsed with fibroblast lysate (5 pg, 50 pg, or 100 pg) from Doxorubicin-Treated Fibroblasts Compared Against Control (unpulsed) cultures.[001138] FIG. 9: Expression of the Cell Cycle Regulator pl6 in Dendritic Cells after pulsing with fibroblast lysateExample 2: Suppression of lung cancer growth in a murine model by administration of a dendritic cell vaccine comprising dendritic cells pulsed with lysate from senescent fibroblasts.[001139] The Lewis lung carcinoma (LLC) model was used, which is a reproducible syngeneic murine model for lung cancer. The established LLC cell line is anaplastic, highly tumorigenic, and immunologically compatible with the murine system.[001140] Several experiments were performed that utilized DCs that were generated from mice in either 5-day or 7-day cultures in GM-CSF and IL-4. These different cultures times were performed to determine whether differences in functional maturity between DCs affected their functions or efficacy for use as cellular vaccines. The DCs were subsequently cultured with lysates from senescent fibroblasts using methods of the invention involving doxorubicin treatment to induce senescence of the fibroblasts. Coculture of DCs with lysates from senescent fibroblasts was performed to induce uptake of senescence-related antigens by the DCs, and to create a population of antigen presenting cells that is useful as a cellular vaccine to target senescent cells in vivo. All experiments were performed using DC vaccines generated from a syngeneic source. Another aspect of these experiments involved single or multiple administrations of the cellular vaccine to assess the growth of lung cancer in the model system.[001141] In the first experiment, dendritic cells were generated from murin...

Claims

WHAT IS CLAIMED IS:

1. A method for treating a subject with cancer by targeting senescent cells in the tumor microenvironment using an autologous vaccine, the method comprising: a) identifying a subject with cancer; b) isolating peripheral blood mononuclear cells comprising a precursor cell from the subject; c) inducing in vitro differentiation of the precursor cell into an antigen presenting cell; d) providing the antigen presenting cell with lysate comprising one or more antigens from a senescent cell, wherein the dendritic cell takes up and incorporates the one or more antigens, and wherein the one or more antigens is selected from the group consisting of: p l 6Illk4ap21Cipl, and high mobility group box 1 (HMGB1); and e) administering a therapeutically effective amount of the antigen presenting cell to the subject, wherein the antigen presenting cell stimulates an immune response against senescent cells in the tumor microenvironment.

2. The method of Claim 1, wherein the senescent cell is selected from the group consisting of: a) a fibroblast; b) a bone marrow cell; c) an endothelial cell; d) a myeloid cell; e) a macrophage; f) a basal cell; g) a hair follicle cell; h) a pneumocyte; i) an epithelial cell; j) a T cell; k) a B cell; 1) a microglial cell; m) a choroid plexus cell; n) a plasma cell; o) a neuron; p) a neutrophil; q) a spinous cell; r) a smooth muscle cell; s) an NK cell; t) an NK T cell; u) a cardiomyocyte; v) a pericyte; w) an endothelial progenitor cell; x) a tumor cell; and y) a mesenchymal stromal cell.

3. The method of Claim 1, wherein the senescent cell comprises a fibroblast.

4. The method of Claim 3, wherein the fibroblast comprises a dermal fibroblast.

5. The method of Claim 4, wherein the dermal fibroblast is obtained by a punch biopsy of skin from the subject.

6. The method of Claim 3, wherein the fibroblast is derived from the periphery of a tumor.

7. The method of Claim 3, wherein the fibroblast expresses one or a plurality of molecules selected from the group consisting of: a) CDllc; b) c-kit; c) c-met; d) OCT-4; e) NANOG; f) KLF4; g) SSEA4; h) TRA-1; i) PIM-1; j) PD-GF receptor; and k) SLC14A4.

8. The method of Claim 3, wherein the fibroblast expresses HL A class II antigens.

9. The method of Claim 3, wherein the lysate is derived from a cell that is rendered senescent by treatment with doxorubicin.

10. The method of Claim 9, wherein doxorubicin is provided at a concentration between 100 nM and 200 nM.

11. The method of Claim 3, wherein the lysate is derived from a cell that is rendered senescent by treatment with one or a plurality of the following stimuli or agents selected from the group consisting of: a) ionizing radiation; b) non-ionizing radiation; c) a genotoxic drug; d) a demethylating agent; and e) an acetylating agent.

12. The method of Claim 1, wherein the antigen presenting cell is a dendritic cell.

13. The method of Claim 1, wherein the antigen presenting cell is selected from the group consisting of: a) a B cell; b) a macrophage; c) a monocyte; d) a neutrophil; e) a natural killer (NK) cell; f) an endothelial cell; g) an epithelial cell; h) a fibroblast; i) an eosinophil; j) a mast cell, and k) a dendritic cell.

14. The method of Claim 1, wherein the antigen presenting cell exhibits surface expression of CD80, CD86, and HLA class II molecules.

15. The method of Claim 1, wherein induction of differentiation of the precursor cell is performed using GM-CSF and IL-4.

16. The method of Claim 1, wherein the tumor microenvironment comprises cells having a senescence-associated secretory phenotype (SASP).

17. The method of Claim 16, wherein the SASP comprises a molecule selected from the group consisting of: a) interleukin-6 (IL-6); b) IL-8; c) IL-1; d) TNF-alpha; e) a TNF receptor; f) an insulin-like growth factor binding protein (IGFBP); g) Cystatin-C; and h) GDF-15.

18. The method of Claim 16, wherein the SASP comprises a molecule selected from the group consisting of: a) an interleukin; b) a chemokine; c) a growth factor; d) a secreted protease; and e) a secreted insoluble molecule.

19. The method of Claim 1, wherein the immune response against senescent cells in the subject is directed against a molecule selected from the group consisting of: a) a member of the BCL-2 family of proteins; b) a Heat Shock protein; c) Bromodomain containing 4 (BRD4); d) Na / K ATPase; e) Oxidation resistance 1 (0XR1); f) IL-6; g) IL-8; h) IL-1; and i) TNF-alpha.

20. The method of Claim 1, wherein the senescent cell used to generate lysate expresses a biomarker or antigen selected from the group consisting of: a) Senescence-associated beta-galactosidase (SA-Pgal); b) DEC1 / DEC2; c) ARF; d) p 15; e) Senescence-associated heterochromatin foci (SAHF); f) IL-6; g) IL-8; h) TNF-alpha; p53; and i) telomere-induced foci.

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