A Phase II Trial Assessing Autologous, Tumor-Pulsed Dendritic Cells as a Tumor Vaccine Administered With IL-2 in Patients With Metastatic Colorectal Cancer

Pretreatment screening: If a subject decides to participate in this study they will first be presented the informed consent document to read and review with the Principal Investigator (or his designee) to go over each aspect of the study and answer any questions. Once the patient has consented, they will first be screened to make sure they meet the eligibility criteria. The screening process is done to make sure that it is appropriate for the subject to participate in this study. This process will include a review of their medical history, a complete physical examination, standard blood tests, an EKG (an electrocardiogram), a chest x-ray and if it is possible for them to become pregnant, a pregnancy test. These tests are normally performed on patients prior to receiving chemotherapy for cancer. In addition to these tests which are normally performed, blood will be obtained for tests which are specific for this investigational study.

These study specific tests include a blood test to determine whether a subject may be infected with the hepatitis B virus or the AIDS virus, and blood tests to determine the ability of their immune system to respond to normal stimulation. A doctor will also order CT scans or nuclear medicine scans to measure the extent of the subject's cancer because the study therapy has a possibility of shrinking the tumor and this will be determined by measuring each subject's disease before and after therapy.

At the time of this initial evaluation subjects will have skin tests that will determine their ability to mount an immune response to infectious agents (such as tetanus, measles, mumps) that they have been exposed to or vaccinated against. If a subject fails to demonstrate a response to all the skin tests, they will not be allowed to participate in this study because such lack of response indicates that their immune system may not respond to the therapy planned in this study.

Vaccine therapy: In order to make a vaccine from a subject's tumor they must have surgical removal of some tumor in order to provide tumor cells. The doctor will determine if a subject has colorectal cancer cells that are easily obtainable. However, if a subject already has an available frozen tumor specimen at the University of Michigan, that may be used for the vaccine preparation instead of undergoing another surgical procedure. This surgery may be done solely for the purpose of participating in this research and may not otherwise benefit a subject. A separate consent form will be required for any surgery a subject undergoes.

The cancer cells obtained from each subject will be taken to the laboratory where they will be separated into single cells, disrupted to make cell fragments, radiated to kill the cells and then mixed with your dendritic cells. The dendritic cells will be obtained from the peripheral blood. Subjects will undergo a procedure called leukapheresis that involves placing a large needle (central line) in a vein in each of their arms. These central lines will be inserted under local anesthesia (subjects will remain awake...only the site of the insertion will be "frozen"). Blood exits from one needle and is processed through a machine that selectively removes one kind of white blood cell and then returns the other elements of the blood back to their body. The leukapheresis procedure generally lasts three to four hours. Following the procedure, the dendritic cells will be cultured in the laboratory to increase the number of dendritic cells. This procedure takes about 2 days.