Autologous T Cells Expressing MET scFv CAR (RNA CART-cMET)

This is a pilot study to evaluate feasibility, safety, and preliminary evidence of efficacy
for intravenously administered, RNA electroporated autologous T cells expressing MET chimeric
antigen receptors with tandem TCRζ and 4-1BB (TCRζ /4-1BB) co-stimulatory domains (referred
to as "RNA CART-cMET") in patients with advanced melanoma or breast carcinoma. Subjects will
be treated with IV administration of the RNA transduced anti-cMET CAR T cells for a total of
up to six doses over a 2 week period.

Each dose is 1x108 total T cells modified with RNA anti-cMET CAR. All subjects in both the
melanoma and breast carcinoma arms will receive up to 6 doses of RNA CART-cMET cells, with no
lymphodepleting chemotherapy administered prior to cell infusion Cell numbers are based on
total cells with a portion of them having CAR expression depending on transduction efficiency
and determined by flow cytometry Based on the product release criteria, at least 20% of the
total cells will express the anti-cMET CAR. Treatment limiting toxicity (TLT). Adverse event
reporting will begin at the start of the first dose of RNA CART-cMET and will continue until
4 months after the first infusion, or until another alternative therapy is initiated,
whichever occurs earlier. Subjects will be continually reassessed for evidence of acute and
cumulative toxicity.

Inclusion Criteria:

- Unresectable histologically confirmed stage III/IV melanoma or metastatic or locally
advanced unresectable ER and PR negative, HER2 neu nonamplified by IHC and/or FISH
breast carcinoma

- cMET expression in ≥ 30% tumor cells as demonstrated on immunohistochemistry analysis
at the University of Pennsylvania. MET IHC may be performed on tissue from screening
biopsy, or archival slides of a metastatic deposit or primary tumor. Punch biopsy or
percutaneous core biopsy will be offered to obtain tissue as required for this
purpose.

- Patients must have measureable disease as defined by RECIST 1.1 criteria; must have CT
scan of chest, abdomen, pelvis within 1 month of enrollment that demonstrates
measurable disease by RECIST 1.1 criteria in a tumor other than the one being
potentially biopsied and resected for correlative studies

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

- If previously treated with any form of immunotherapy (including agents targeting PD1
or CTLA4, oncolytic viruses) the last administered treatment must be at least 2 weeks
prior to enrollment

- Males or female patients age > 18 years old

- Eastern Cooperative Oncology Group (ECOG) Clinical Performance Status 0 or 1

- Adequate hematologic and organ function as defined by:

- WBC > 3.0 and ANC >1500

- Plt > 75,000 (no transfusion permitted within 2 weeks to achieve this goal)

- Hgb > 9 g/dl (transfusions are permitted to achieve this goal)

- serum creatinine ≤ 1.5 times upper limit of normal

- Total bilirubin ≤ 2times upper limit of normal

- ALT and AST ≤ 2 times upper limit of normal

- Cardiac ejection fraction of >40% as measured by resting echocardiogram

- Women of child bearing potential must have a negative serum or urine pregnancy test
and agree to use appropriate contraception from enrollment through the duration of the
trial. Men must agree to use appropriate contraception from enrollment through the
duration of the trial.

- Patients must provide written informed consent.

Exclusion Criteria:

- Known metastatic tumor encasing a great vessel or at risk for imminently causing
spinal cord compression

- Known HIV-1/HIV-2 infection

- Known active infection with Hepatitis B virus or Hepatitis C virus

- Received an experimental therapy within 30 days of enrollment

- Pregnant women or lactating women

- History of alcohol abuse or illicit drug use within 12 months of enrollment

- Clinically significant comorbid disease or other underlying condition, including
significant active infection, in the opinion of the PI or sub-investigators, would
contraindicate study therapy or interfere with interpretation of study results

- Significant psychiatric disorder and/or any other reason in the Investigator's opinion
that would jeopardize protocol compliance or compromise the patient's ability to give
informed consent.

- Patients with known allergy or hypersensitivity to study product excipients (human
serum albumin, DMSO, and Dextran 40).

- Patients with clinically apparent arrhythmia, or arrhythmias that are not stable on
medical management within 2 weeks of the Screening/Enrollment visit.

- Having received prior genetically manipulated T-cells in prior clinical trial

- History of autoimmune disease (including but not limited to: systemic lupus
erythematosis, Sjogren syndrome, rheumatoid arthritis, psoriasis multiple sclerosis,
inflammatory bowel disease etc).

- History of immune related adverse event with previous immunotherapy.

- Chronic use of therapeutic anti-coagulants such as coumadin, heparin, or lovenox

- Symptomatic or untreated CNS metastases. Pts with previously treated CNS metastases
are eligible if lesions are radiographically/clinically stable without requirement of
steroids within 4 weeks prior to treatment