CART-meso in Mesothelin Expressing Cancers

Inclusion Criteria:

- Histologically confirmed cancer (one of the following):

- Metastatic pancreatic adenocarcinoma.

- Persistent or recurrent serous epithelial ovarian cancer or primary peritoneal
carcinoma

- Malignant pleural mesothelioma (histologically confirmed epithelial)

- Failure of at least one prior standard of care chemotherapy for advanced stage
disease.

- Subjects must have measureable disease as defined by RECIST 1.1 criteria or modified
RECIST criteria.

- Patients > 18 years of age.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

- Life expectancy > 3 months.

- Satisfactory organ and bone marrow function as defined by the following (of note, the
minimal blood counts should be in the absence of transfusion or cytokine support):

i. Absolute neutrophil count > 1,000/μl ii. Platelets >75,000/μl iii. Hemoglobin > 9
g/dL iv. Bilirubin < 2.0x the institutional normal upper limit unless secondary to
bile duct obstruction by tumor v. Creatinine < 1.5x the institutional normal upper
limit vi. Albumin ≥2 vii. Serum alanine aminotransferase (ALT) or aspartate
aminotransferase (AST) < 5x the institutional normal upper limit viii. Cardiac
ejection fraction of >55% as measured by resting echocardiogram, with no significant
pericardial effusion.

- Blood coagulation parameters: PT such that international normalized ratio (INR) is ≤
1.5 and a PTT < 1.2 time the upper limit of normal unless the patient is
therapeutically anti-coagulated for history of cancer-related thrombosis and has
stable coagulation parameters.

- Ability to understand and the willingness to provide written informed consent.

- Male and Female subjects of reproductive potential agree to use approved contraceptive
methods (e.g. birth control pills, barrier device, intrauterine device, abstinence)
and abstain from other methods of conception during the study and for 6 months
following the study cell infusion or proof of sterility.

Exclusion Criteria

- Sarcomatoid MPM histology which is known in the literature to not express mesothelin;
biphasic MPM is also excluded.

- Participated in any other trial in which receipt of an investigational study drug
occurred within 28 days prior to enrollment and anticipated treatment with another
investigational product while on study. This refers to non-commercially approved
investigational drugs different than those used in this protocol.

- Anticipated need for systemic chemotherapy within 2 weeks before apheresis and
infusion of CART-meso cells.

- Active invasive cancer other than the one of the three cancers in this study. Patients
with active non-invasive cancers (such as non-melanoma skin cancer, superficial
cervical and bladder and prostate cancer with PSA level < 1.0) are not
excluded.CART-meso in mesothelin expressing cancers

- HIV, HCV, or HBV infections

- Active autoimmune disease (including but not limited to: systemic lupus
erythromatosis, Sjogren's syndrome, rheumatoid arthritis, psoriasis, multiple
sclerosis, inflammatory bowel disease, etc.) requiring immunosuppressive therapy
within the past 4 weeks, with exception of thyroid replacement.

- Patients with ongoing or active infection.

- Planned concurrent treatment with systemic high dose corticosteroids. Patients may be
on a stable low dose of steroids (<10mg equivalent of prednisone) for chronic
respiratory conditions.

- Patients requiring supplemental oxygen therapy.

- Prior therapy with gene modified cells.

- Previous experimental therapy with SS1 moiety, murine or chimeric antibodies (human
and humanized antibodies are allowed).

- History of allergy to murine proteins

- History of allergy or hypersensitivity to study product excipients (human serum
albumin, DMSO, and Dextran 40)

- Any clinically significant pericardial effusion; CHF (NY Heart Association Grade
II-IV) or cardiovascular condition that would preclude assessment of mesothelin
induced pericarditis or that may worsen as a result of toxicities expected for this
study. This determination will be made by a cardiologist.

- Any clinically significant pleural or peritoneal effusion that cannot be drained with
standard approaches. An indwelling drainage device placed prior to enrollment is
acceptable.

- Pregnant or breastfeeding women. Female study participants of reproductive potential
must have a negative urine pregnancy test of enrollment. A serum pregnancy test will
be performed within 2 weeks before infusion.