Humanized Anti-GD2 Antibody Hu3F8 and Allogeneic Natural Killer Cells for High-Risk Neuroblastoma

Inclusion Criteria:

- Diagnosis of NB as defined by international criteria,.e., histopathology (confirmed by
the MSKCC Department of Pathology) or bone marrow metastases plus high urine
catecholamine levels.

- High-risk NB as defined by risk-related treatment guidelines1 and the International NB
Staging System, i.e., stage 4 with (any age) or without (>365 days of age) MYCN
amplification, MYCN-amplified stage 3 (unresectable; any age), or MYCN-amplified stage
4S.

- Patients must have a history of tumor progression or persistent disease or failure to
achieve complete response following standard therapy.

- Patients must have evaluable (microscopic marrow metastasis, elevated tumor markers,
positive MIBG or PET scans) or measurable (CT, MRI) disease documented after
completion of prior systemic therapy.

- Disease staging approximately within one month of treatment

- Prior treatment with murine and hu3F8 is allowed. Patients with prior m3F8, hu3F8,
ch14.18 or hu14.18 treatment must have HAHA antibody titer ≤1300 Elisa units/ml. Human
anti-mouse antibody positivity is allowed.

- Eligible NK donor

- Children and adults are eligible

- Signed informed consent indicating awareness of the investigational nature of this
program.

Donor Inclusion Criteria

- Donor is blood-related and HLA-haploidentical to the recipient.

- Donor has undergone serologic testing for transmissible diseases as per blood banking
guidelines for organ and tissue donors. Tests include but are not limited to:
Hepatitis B Surface Antigen, Hepatitis B Surface Antibody, Hepatitis B Core Antibody,
Hepatitis C antibody, Epstein-Barr Virus Antibody, HIV, HTLV I and II, Varicella
Zoster (Herpes Zoster), Herpes Simplex Antibody, Cytomegalovirus Antibodies, Syphilis
(RPR profile) for adolescents and adults, measles for pediatric patients, West Nile
Virus, Chagas screen, and Toxoplasma antibodies. Donor must have normal negative test
results for HIV, HTLV I and II, and West Nile Virus. Donor exposure to other viral
pathogens will be discussed on a case-by-case basis by investigators.

- Donor must be able to undergo leukopheresis for total volume of 10-15 liters.

- There is no age restriction for the donor.

Exclusion Criteria:

- Patients with CR/VGPR disease

- Existing severe major organ dysfunction, i.e., renal, cardiac, hepatic, neurologic,
pulmonary, or gastrointestinal toxicity > grade 3 except for hearing loss, alopecia,
anorexia, nausea, hyperbilirubinemia and hypomagnesemia from TPN, which may be grade 3

- ANC should be >500/uL

- Platelet count >75K/uL.

- History of allergy to mouse proteins

- Active life-threatening infection

- Inability to comply with protocol requirements

- Women who are pregnant or breast-feeding

Donor Exclusion Criteria:

- Cardiac risk factors precluding ability to undergo leukopheresis

- Concurrent malignancy or autoimmune disease

- Donor is pregnant