Vaccine Enriched, Autologous, Activated T-Cells Directed to Tumor in Patients With Relapsed/Refractory Melanoma

The rate of progression free survival at one (1) year is < 20% for patients with stage IV
metastatic melanoma, despite aggressive cytotoxic chemotherapy regimens and newly approved
immunomodulatory and targeted therapy. Immunotherapy seems to hold the most promise for
achieving prolonged survival or even cure, therefore,efforts have focused on several
different approaches. Such approaches have used tumor vaccination, adoptive transfer of
tumor infiltrating lymphocytes, and even monoclonal antibodies, unconjugated or conjugated
to cytokines, toxins, or radionucleotides.

The tumor-associated antigen GD2 has been noted on the surface of several tumors, most
notably neuroblastoma, but is expressed on melanoma as well. Clinical studies have shown
activity of a GD2-specific chimeric T-cell receptor expressed on activated, autologous,
T-cells in patients with neuroblastoma. It is the investigators intention to enrich
peripheral blood mononuclear cells (PBMC) of patients with stage IV metastatic melanoma with
vaccine-specific T-cells through pre-harvest/ phlebotomy vaccination with common, well
understood vaccines. The investigators will then modify the T-cells to attack the GD2
antigen. These tumor redirected, vaccine specific, activated T-cells will then be infused
into the patient following revaccination with the common vaccines. The Investigators will
monitor expansion of the modified T-cells through serial polymerase chain reaction (PCR)
assays following vaccination.

The Investigators then intend to re-vaccinate with the selected vaccines one month following
infusion and monitor for expansion of the modified T-cells.

Inclusion Criteria:

- Metastatic, surgically unresectable melanoma or newly diagnosed melanoma of any
stage, where the patient is unable to receive or complete standard therapy

- Life expectancy of at least 12 weeks.

- Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2

- Laboratory Values

- absolute neutrophil count > 500 microliters (mcL)

- platelet > 50,000 mcL

- serum aspartate aminotransferase (AST) < 5 x institutional upper limit of normal
(IULN)

- total bilirubin < 3 x IULN

- serum creatinine < 3 x IULN

- Pulse oximetry of > 95% on room air.

- Must have recovered from the toxic effects of all prior chemotherapy

Exclusion Criteria:

- Patients with rapidly progressive disease.

- Patient is currently receiving any investigational drugs

- Current cardiomegaly or bilateral pulmonary infiltrates on chest radiograph,
pulmonary metastatic lesions are allowed

- Patients must not have tumor in a location where enlargement could cause airway
obstruction

- Patient is pregnant or lactating

- History of hypersensitivity reactions to murine protein-containing products.

- Currently receiving immunosuppressive drugs such as corticosteroids (excluding
topical treatment), tacrolimus or cyclosporin

- Received any tumor vaccines within previous six weeks

- Known hypersensitivity to rat monoclonal antibodies

- History of severe allergic reaction to Hepatitis B vaccine, Polio vaccine or Tetanus,
Diphtheria, Pertussis vaccine (DTP, Tdap, DT or Td).

- Allergy to baker's yeast or other components of the vaccines.

- History of allergy to the antibiotics Neomycin, Streptomycin or Polymyxin B

- History of coma, long/multiple seizures within 7 days after DTP or Tdap, unless a
cause other than the vaccine was indicated.

- Melanoma involvement of the central nervous system

- Chemotherapy given within the last 28 days

- Presence of human anti-mouse antibody (HAMA) prior to enrollment (only patients who
have received prior therapy with murine antibodies)