Immunotherapy Based on Antigen-specific Immune Effector Cells Targeting Neurofibromatosis or Schwannomatosis

Prior treatment

• Participation in any other cell therapy protocols within one year.
• Current or recent treatment (within the 28-day period prior to Day 0) with another investigational drug.
• Patients who have had a major surgery or significant traumatic injury within 4 weeks of start of study.

Other illness

• Subject infected with HIV (HIV antibody positive), Treponema pallidum antibody positive or TB culture positive.

Lab values

• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
  • Symptomatic congestive heart failure of New York heart Association Class III or IV
  • unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
  • severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air
  • uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN (Note: Optimal glycemic control should be achieved before starting trial therapy.)
  • active (acute or chronic) or uncontrolled severe infections
  • liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C).
• Inadequate bone marrow function:
  • Absolute neutrophil count < 1.0 x 10e9/L.• Platelet count < 100 x 10e9/L.
  • Hb < 9 g/dL.
• Inadequate liver and renal function:
  • Serum (total) bilirubin > 1.5 x ULN.
  • AST \& ALT > 2.5 x ULN (> 5 x ULN in patients with liver metastases).
  • Alkaline phosphatase > 2.5 x ULN (or > 5 x ULN in case of liver metastases or > 10 x ULN in case of bone metastases).
  • Serum creatinine >2.0 mg/dl (> 177 μmol/L).
  • Urine dipstick for protein uria should be < 2+. Patients with ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo 24 hour urine collection and must demonstrate < 1 g of protein/24 hr.

Other

• The results of immune staining of the patient's tumor-associated antigens are all negative.
• Pregnant or lactating females.
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.

• Written, informed consent obtained prior to any study-specific procedures.
• Diagnosis of neurofibromatosis, or schwannomatosis
• The results of immune staining of the patient's cancer specimens positive for any one or more of a list of tumor-associated antigens.
• Age ≥ 1 years
• At least one volumetrically measurable and ≥ 0.5 cc NF-related tumor (schwannoma, ependymoma, meningioma - histological confirmation not required) with radiographic evidence of progression (either as unequivocal progression on conventional MRI, or a >10% volume increase by 3D volumetrics) over the past ≤12 months, designated as the primary target tumor OR Volumetrically measurable and ≥ 0.5 cc VS with ipsilateral progressive hearing loss over the past ≤12 months, designated as the primary target tumor.
• Progressive Hearing Loss Criteria for Enrollment: Audiogram showing drop in pure tone average (PTA) of 10dB HL at ≥ 2 nonconsecutive or consecutive frequencies or drop in speech discrimination score (SDS) below the 95% critical difference threshold, compared to previous audiogram ≤ 1 year prior.
• Karnofsky/Lansky performance status (PS) 50-100%. Note: Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Any neurologic deficits must be stable for ≥ 1 week.
• Adequate bone marrow reserve with
  • absolute neutrophil count (ANC) ≥ 1000/mm3.
  • Platelets ≥100,000/mm3.
• Adequate renal and hepatic function with
  • Serum creatinine ≤ 2 x upper limit of normal (ULN).
  • Serum bilirubin ≤ 2 x ULN.
  • aspartate aminotransferase (AST)/ALT ≤ 2 x ULN.
  • Alkaline phosphatase ≤ 5 x ULN.
  • Serum bilirubin 2.0 is acceptable in the setting of known Gilbert's syndrome.