Inclusion Criteria:
Cohorts 1 and 2, Part A:
* Age ≥ 18 years old.
* Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
* Have histologically confirmed locally advanced, unresectable, or metastatic solid tumor.
* For subjects with genetic mutations or alterations in solid tumors (e.g. NSCLC, pancreatic cancer, melanoma), the subjects must have received prior appropriate disease specific targeted therapy and have progressed.
* Have at least 1 measurable lesion and/or non-measurable disease evaluable in accordance with RECIST Version 1.1.
* For subjects with a history of human immunodeficiency virus (HIV)
* Subjects with CD4+ T-cell (CD4+) counts ≥ 350 cells/uL and without a history of AIDS defining opportunistic infections.
* For subjects with a history of hepatitis B virus (HBV)
* Subjects who are chronic carriers of HBV infection (HBsAg-positive, undetectable or low HBV DNA, and normal ALT) who are not on HBV therapy, or in individuals who have serologic evidence of a resolved prior HBV infection (i.e., HBsAg-negative and anti-HBc-positive), anti-HBV prophylaxis should be assessed prior to enrollment.
* Subjects with chronic HBV infection with active disease who meet the criteria for anti HBV therapy should be on a suppressive antiviral therapy prior to enrollment.
* For subjects with a history of hepatitis C virus (HCV)
* Subjects with a history of HCV infection should have completed curative antiviral treatment and have a HCV viral load below the limit of quantification are eligible.
* Subjects who are HCV Ab positive but HCV RNA negative due to prior treatment or natural resolution are eligible.
* Subjects on concurrent HCV treatment and have HCV below the limit of quantification are eligible.
Note: Subjects who have a history of HIV/HBV/HCV or are seropositive will require Infectious Disease Marker (IDM) testing prior to apheresis collection.
* Subjects who currently have non-progressive brain metastasis and were previously treated with surgical resection/debulking, radiation, and stereotactic radiosurgery.
* Able to undergo an Apheresis procedure:
* Have adequate venous access
* Able to sit or recline for 5-6 hours with limited movement
* Hemoglobin must be ≥ 9.0 g/dL
* Platelet count must be ≥ 100,000 cells/mm3
* Vital signs must be within normal range
* Negative serum pregnancy test for females of childbearing potential.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
* Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
* Agreement to practice effective contraception for female subjects of child-bearing potential and non-sterile males. Female subjects of child-bearing potential must agree to use effective contraception for up to 30 days after completion of therapy, and non- sterile male subjects must agree to use a condom for up to 30 days after treatment. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), 2 forms of barrier methods (eg, condom, diaphragm) used with spermicide, and intrauterine devices (IUDs).
Cohort 2, Part B subjects only:
* Have documented progressive disease after receiving treatment with at least 2 prior lines of therapy or not be a candidate for therapy of proven efficacy for their disease. Prior immune therapy and prior treatment with a checkpoint inhibitor as per FDA indication for current standard of care therapy is allowed.
* Subjects cannot receive M-CENK before a 14-day washout period following treatment with an approved chemotherapy and approved or investigational immunotherapy (eg PD-1/PD-L1 inhibitors, CAR NK cells \[PD-L1 t-haNK\], N-803). A repeat lab at least 14 days after completion of the washout period is required.
* Subjects cannot receive M-CENK before a 30-day washout period following treatment with investigational chemotherapy. A repeat lab at least 30 days after completion of the washout period is required.
* Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
* Agreement to practice effective contraception for female subjects of child-bearing potential and nonsterile males. Female subjects of child-bearing potential must agree to use effective contraception for up to 30 days after completion of therapy, and non- sterile male subjects must agree to use a condom for up to 30 days after treatment. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), 2 forms of barrier methods (eg, condom, diaphragm) used with spermicide, and intrauterine devices (IUDs).
Exclusion Criteria (Cohorts 1 and 2, Part A):
There is no exclusion criteria for cohorts 1 and 2, part A.
Exclusion Criteria (Cohort 2, Part B only):
\*Note: All subjects must meet eligibility criteria at the time of enrollment. Additionally, all subjects will be re-evaluated to confirm that they still meet the eligibility criteria specified with an asterisk below once the M-CENK cells are manufactured and prior to to the first administration of M-CENK. The Sponsor will approve the subject's continued eligibility prior to receiving the manufactured M-CENK cells.
* \*Life expectancy \< 16 weeks based on the best judgment of the Investigator.
* \*Involuntary weight loss of \> 10% usual body weight between the time of enrollment and at the time of administration of M-CENK cells
* \*Calorie or protein restrictive dietary regimen.
* \*Serious uncontrolled concomitant disease that would contraindicate the use of the investigational drug used in this study or that would put the subject at high risk for treatment- related complications.
* Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, autoimmune disease associated with lymphoma) requiring medical treatment.
* \*Currently receiving or has received antibiotics since enrolling in the study or documented infection.
* History of organ transplant requiring immunosuppression.
* History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis), unless the inflammation is well controlled.
* \*Inadequate organ function, evidenced by the following laboratory results:
* Absolute neutrophil count (ANC) \< 1000 cells/mm3.
* Platelet count \< 100,000 cells/mm3.
* Hemoglobin \< 9 g/dL.
* Total bilirubin \> 1.5 x the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome).
* AST (SGOT) or ALT (SGPT) \> 2.5 × ULN (\> 5 × ULN in subjects with liver metastases).
* Alkaline phosphatase (ALP) levels \> 2.5 × ULN (\> 5 × ULN in subjects with liver metastases, or \>10 × ULN in subjects with bone metastases).
* Serum creatinine \> 2.0 mg/dL or 177 μmol/L.
* Albumin \< 2.8 g/dL. Note: Each site should use its own institution's upper limit of normal (ULN) to determine eligibility.
* \*Subjects with ascites requiring paracentesis or pleural effusion requiring thoracentesis.
* \*Uncontrolled hypertension (systolic \> 160 mm Hg and/or diastolic \> 110 mm Hg) or clinically significant (ie, active) cardiovascular disease, cerebrovascular accident/stroke, or myocardial infarction within 6 months prior to first study medication; unstable angina; congestive heart failure of New York Heart Association grade 2 or higher; or serious cardiac arrhythmia requiring medication.
* \*Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy. Oxygen therapy on an as needed or intermittent basis is allowed.
* \*Current chronic daily treatment (since enrolling in the study) with systemic corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled steroids. Short-term steroid use to prevent IV contrast allergic reaction or anaphylaxis in subjects who have known contrast allergies is allowed.
* \*Known hypersensitivity to any component of the study medication(s).
* \*Participation in an investigational drug study or history of receiving any investigational treatment or cytotoxic chemotherapy within 14 days prior to dosing for this study, except for hormone-lowering therapy in subjects with hormone-sensitive cancer.
* \*Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
* \*Concurrent participation in any interventional clinical trial since enrolling.
* \*Pregnant and nursing women. A negative serum pregnancy test during screening and a negative pregnancy test within 24 hours prior to the first dose must be documented before M-CENK is administered to a female subject of childbearing potential.
