MOv19-BBz CAR T Cells in FRa+ Cancers

Inclusion criteria

• Signed informed consent form
• Documentation of tumor FRa expression by IHC at the Hospital of the University of Pennsylvania (≥ 10% of tumor cells). Subjects must have archived tumor tissue available.
• Disease-specific criteria:

a. NSCLC Patients: i. Metastatic or recurrent lung adenocarcinoma with cytologically or pathologically confirmed malignant pleural effusion.

ii. Failure of at least one prior line of standard of care therapy for advanced stage disease.

• Patients must have evidence of active disease as defined by RECIST 1.1 criteria
• Patients with asymptomatic CNS metastases that have been treated (and are off steroids for the treatment of CNS disease) are allowed. They must meet the following criteria

• No concurrent treatment for the CNS disease
• No progression of CNS metastasis on MRI at screening
• No evidence of leptomeningeal disease or cord compression
• Adequate organ function defined as:

• Serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 30 cc/min; Patient must not be on dialysis
• ALT/AST ≤ 3x upper limit of normal range
• Serum total bilirubin ≤ 1.5 mg/dl, unless the subject has Gilbert's syndrome (if so, serum total bilirubin must be ≤ 3.0 mg/dl)
• Must have a minimum level of pulmonary reserve defined as < Grade 1 dyspnea and pulse oxygen > 92% on room air
• Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO or MUGA
• Male or female age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status that is either 0 or 1
• Subjects must be a possible clinical candidate for standard of care treatment with a commercial checkpoint inhibitor, as per physician-investigator assessment.

Exclusion criteria

• Any clinically significant pleural effusion that cannot be drained with standard approaches.
• Patients with significant lung disease as follows:

• Patients with radiographic evidence of greater than lobar lymphangitic pulmonary involvement, greater than lobar bronchial wall thickening suggestive of peribronchial lymphatic disease extension, and/or evidence of extensive bilateral parenchymal metastatic burden.Note: "Greater than lobar" = "in more than 1 lobe".
• Patients with radiographic and/or clinical evidence of active radiation pneumonitis.
• Patients with radiographic evidence of underlying interstitial lung disease, including evidence of unresolved drug toxicity from any agent (e.g. chemotherapy, targeted agents, amiodarone, nitrofurantoin, etc.).
• Patients with radiographic evidence of significant pleural effusion that is not readily amenable to minimally invasive drainage.
• Active hepatitis B or hepatitis C infection
• Any other active, uncontrolled infection
• Class III/IV cardiovascular disability according to the New York Heart Association Classification
• Active invasive cancer, other than the proposed cancer included in this protocol, within 2 years prior to eligibility confirmation by a physician-investigator. [Note: non-invasive cancers treated with curative intent (e.g., non-melanoma skin cancer) may still be eligible].
• Dependence on systemic steroids or immunosuppressant medications.
• Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods
• Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone daily. Patients with autoimmune neurologic diseases (such as MS) will be excluded.
• History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)