NHS-IL12 for Solid Tumors

* INCLUSION CRITERIA: Participants must meet the following criteria for participation: * Participants must have histologically confirmed malignancy that is metastatic or unresectable locally advanced solid tumors. * Participants must have completed or had disease progression on at least one prior line of disease-appropriate therapy for unresectable locally advanced or metastatic disease, or not be a candidate for therapy of proven efficacy for their disease due to an underlying physical condition. * Participants may have disease that is measurable or non-measurable but evaluable disease (e.g. present on bone scan, rising tumor markers, non-measurable by RECIST but visible on CT scan). Participants with third space fluid (for example pleural effusions) as only site of disease will not be eligible. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 at study entry. * Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of NHS-IL12 in participants \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials. * Participants must have normal organ and marrow function as defined below: 1. Hematological eligibility parameters (within 16 days of starting therapy): * Absolute granulocyte count greater than or equal to 1,500/mcL * Absolute lymphocyte count greater than or equal to 500/mcL * Platelet count greater than or equal to 100,000/mcL * hemoglobin greater than or equal to 9 g/dL 2. Adequate hepatic function defined by a * total bilirubin level less than or equal to 1.5 times ULN or in participants with Gilbert s syndrome, a total bilirubin less than or equal to 3.0, and * aspartate aminotransferase (AST) and alanine-aminotransferase (ALT) levels less than or equal to 2.5 times ULN or, for participants with documented metastatic disease to the liver, AST and ALT levels less than or equal to 5 times ULN. 3. Adequate renal function defined by an estimated creatinine clearance greater than 60 mL/min determined by 24-hour urine sampling or by the Cockcroft-Gault formula: Ccr = (140 age) (weight, kg) (constant)/\[72 times Crserum (mg/100 mL). The constant is 1 for men and 0.85 for women OR Ccr = (140 age) (weight, kg) (constant)/Crserum (micro mol/L). The constant is 1.23 for men and 1.04 for women. CD4 lymphocyte count or other T lymphocyte subset count will not be used to determine eligibility. * Participants must agree to practice effective contraception (both male and female subjects, if the risk of conception exists). The effects of NHS-IL12 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and for 30 days after the last dose. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. * A minimum of 4 weeks will be required from any prior therapy, including chemotherapy, immunotherapy and/or radiation. In addition, recovery to Grade 1 or less from reversible all reversible toxicities related to prior therapy is required at study entry. Prior immune therapy (e.g. related vaccinia and fowlpox vaccines or antigen-specific peptides) is allowed. * Subject must sign a written informed consent document. EXCLUSION CRITERIA: Participants with any of the following will not be eligible for participation in this study: * Participants who are receiving any other investigational concurrent anticancer treatment (chemotherapy, radiotherapy, immunotherapy, cytokine therapy except erythropoietin) at the time of enrollment except for disease specific appropriate hormonal therapies (e.g., ADT for prostate cancer, anti-estrogen for breast cancer, somatostatin analogue for neuroendocrine cancer) * Concurrent use of systemic steroids (within 10 days of enrollment) will be excluded, except for physiologic doses of systemic steroid replacement or local (topical, nasal, or inhaled) steroid use. Limited doses of systemic steroids (e.g., in participants with exacerations of reactive airway disease) must have completed at least 10 days prior to enrollment. Steroid use to prevent IV contrast allergic reaction or anaphylaxis in participants who have known contrast allergies is allowed at any time prior to enrollment. * Participants who have previously received rIL-12 * Acquired immune defects such as HIV or innate immunodeficiency because this agent requires an intact immune system. In addition, these participants are at increased risk of lethal infections when treated with marrow-altering therapy. * Systemic autoimmune disease (e.g., lupus erythematosus, rheumatoid arthritis, Addison s disease, autoimmune disease associated with lymphoma). * History of organ transplant. * History of or active inflammatory bowel disease (e.g., Crohn s disease, ulcerative colitis). * Chronic infections (e.g., hepatitis B or C, tuberculosis). * Known hypersensitivity or allergic reactions attributed to any compounds of similar chemical or biologic composition to the study medication, such as recombinant IL-12 or other monoclonal antibodies * Known hypersensitivity to methotrexate * History of brain metastases because of the poor prognosis of participants with brain metastases and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. * Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke \< 6 months prior to enrollment, myocardial infarction \< 6 months prior to enrollment, unstable angina, congestive heart failure (greater than or equal to NYHA III) or serious cardiac arrhythmia requiring medication. * Pulmonary disease which, in the opinion of the investigator, may impair the patient s respiratory tolerance to moderate pulmonary fluid overload (e.g., interstitial lung disease, severe chronic obstructive pulmonary disease). * All conditions associated with significant necrosis of nontumor-bearing tissues: esophageal or gastroduodenal ulcers \< 6 months prior to enrollment, organ infarction \< 6 months prior to enrollment, or active ischemic bowel disease. * Presence of medically significant third space fluid (symptomatic pericardial effusion, ascites or pleural effusion requiring repetitive paracentesis). * History of active alcohol or drug abuse. * Any significant disease that, in the opinion of the investigator, may impair the patient s tolerance of study treatment. * Significant dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent. * Pregnancy (absence to be confirmed by beta-human chorionic gonadotropin test) or lactation. * Pleural effusion as the only evidence of metastatic disease. * Expansion Cohorts only * Participants must have measurable disease, defined as at least one lesion that can be accurately measured as greater than or equal to 5 times 5 mm.