This is a single site, open label, Phase 1 study using a 3 + 3 dose escalation design in two cohorts of adults with recurrent, platinum-resistant ovarian tumors.

Inclusion Criteria:

1. Disease: Histologically or cytologically confirmed diagnosis of ovarian cancer including serous, endometrioid, clear cell, mucinous, mixed epithelial, or undifferentiated. The study does not include pure sarcoma, stromal, or germ-cell tumors. Tumors that are substantially high-grade carcinoma and have focal elements of lower grade tumors or sarcomatous elements (e.g., carcinosarcoma) are eligible.

2. Have measurable disease. Measurable disease is defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded). Each lesion must be ≥10 mm when measured by CT, MRI, or caliper measurement at clinical examination or ≥20 mm when measured by chest x-ray. Lymph nodes must be ≥15 mm in short axis when measured by CT or MRI.

3. B7-H3 positive expression on malignant cells is NOT required but archival tissue must be available, or the subject must be willing to undergo tissue biopsy for expression analysis.

4. Age: ≥ 18 years of age

5. Prior Therapies: Subjects must have had at least 1 prior platinum-based chemotherapeutic regimen for the management of ovarian carcinoma.

   Patients should be considered platinum- refractory (progression while on a prior platinum chemotherapy) or resistant (persistence or recurrence within 6 months after a prior platinum-based chemotherapy) after all available curative standard therapies. There is no limit to the number of prior therapies.

   At least 3 weeks post chemotherapy or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy, except for systemic inhibitory/stimulatory immune checkpoint therapy that requires 3 months.

   Must have recovered from prior therapy toxicities to grade 1 or baseline, except for peripheral neuropathies, alopecia, etc.

6. Performance Status: ECOG status of 2 or better (or Karnofsky Performance Status score of ≥60%) (See Section 11.1)

7. Life expectancy at least 3 months, in the investigator's clinical judgement.

8. Adequate bone marrow and major organ function.

   • Hgb ≥ 10 g/dL
   • ANC ≥ 1500/uL
   • Platelet count ≥ 100,000/uL
   • Absolute lymphocyte count ≥150/uL
   • Creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 50 mL/min
   • Serum ALT and AST ≤ 5x ULN (Grade 2)
   • Total bilirubin ≤ 1.5x ULN (subjects with Gilbert's syndrome allowed if direct bilirubin within normal limits)
   • PT or PTT ≤ 1.25 X ULN (not receiving therapeutic anticoagulation)
   • Cardiac ejection fraction ≥ 45%
   • No evidence of physiologically significant pericardial effusion
   • No clinically significant ECG findings
   • Baseline oxygen saturation > 92% on room air

9. Pregnancy: Females of childbearing potential (defined as women ≤50 years of age, or >50 years of age with a history of amenorrhea for ≤12 months prior to study entry) must have a negative blood or urine pregnancy test.

Subjects of child bearing potential must be willing to use an effective method of contraception (hormonal or two barrier methods) from the time of enrollment on this study and for at least four (4) months after receiving last dose of B7-H3CART cells or until CAR T cells are undetectable in peripheral blood.

10. Consent: Must be able to understand and be willing to personally sign the written IRB approved informed consent document.

Exclusion Criteria:

• 1. Active infection or uncontrollable infection requiring systemic treatment within 1 week before screening. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.

  2. Requirement for systemic corticosteroid therapy at doses higher than physiologic maintenance dosing (must be < 5 mg/day of prednisone (or equivalent doses of other corticosteroids). Topical, inhaled or ocular steroids are allowed.

  3. Presence of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess.

  4. Malignant tumors other than the target tumor within 2 years prior to screening, except for the following: malignant tumors that have received radical treatment and no known active disease within ≥ 2 years prior to enrollment; or adequately treated non-melanoma skin cancers with no evidence of disease.

  5. Have any of the following heart conditions:

  • New York Heart Association (NYHA) stage III or IV congestive heart failure;

  • Myocardial infarction or coronary artery bypass grafting (CABG) within 6 months before enrollment;

  • Clinically significant ventricular arrhythmia, or a history of unexplained syncope (except those caused by vasovagal or dehydration);

  • History of severe nonischemic cardiomyopathy. 6. Known to have active or uncontrolled autoimmune diseases, such as Crohns disease, rheumatoid arthritis, systemic lupus erythematosus, systemic vasculitis, etc.

    7. Ongoing HIV, HBV, or HCV infection. History of HBV or HCV is permitted if viral load is undetectable by qPCR and/or nucleic acid testing.

    8. Known or suspected untreated brain metastases. Patients with radiographically stable, asymptomatic previously irradiated lesions are eligible provided patient is >4 weeks beyond completion of cranial irradiation and >3 weeks off of corticosteroid therapy at the time of study intervention.

    9. Known sensitivities to any of the agents used in this study or their reagents including steroids, tocilizumab, DSMO, cyclophosphamide, fludarabine, etc.

    10. Prior history of clinically significant seizure disorder (e.g., not including childhood febrile seizures).

    11. Any other issue which, in the opinion of the treating physician or principal investigator, would make the patient ineligible for the study.