Trial Information

VACCINE THERAPY WITH TUMOR SPECIFIC MUTATED P53 OR RAS PEPTIDES ALONE OR IN COMBINATION WITH CELLULAR IMMUNOTHERAPY WITH PEPTIDE ACTIVATED LYMPHOCYTES (PAL CELLS) ALONG WITH SUBCUTANEOUS IL-2

OBJECTIVES: I. Determine whether endogenous cellular immunity to a particular tumor-specific
mutated p53 or ras protein is present in patients with tumors expressing mutant p53 or ras.
II. Determine whether vaccination with antigen-presenting cells pulsed in vitro with
synthetic peptide corresponding to the tumor's p53 or ras mutation in the presence of
sargramostim (GM-CSF) can induce or boost patient cellular immunity to the mutated peptide
in this patient population. III. Assess the type and characteristics of the cellular
immunity generated. IV. Determine whether in vivo-primed T-cells generated against the p53
or ras mutation, expanded in vitro with corresponding peptide, and infused with subcutaneous
interleukin-2 can enhance the activity of specific cytotoxic T-lymphocyte immune response
and/or tumor response in these patients.

OUTLINE: Patients are assigned to 1 of 2 treatment regimens. The first 5 patients accrued
are assigned to Regimen A. Three weeks after all 5 patients are enrolled, additional
patients are accrued and assigned to Regimen B. All patients undergo peptide
hypersensitivity testing with the peptide they will be treated with prior to each
vaccination. Regimen A: Two days prior to each vaccination, peripheral blood mononuclear
cells (PBMC) are harvested. PBMC are incubated for 48 hours with either patient-specific
mutant p53 or ras peptide fragments and sargramostim (GM-CSF). The antigen-presenting cells
(APC) are irradiated prior to use. APC are reinfused on day 0. Treatment repeats after 3
weeks and then every 6 weeks for a total of 4 vaccinations. Regimen B: Patients are
vaccinated with APC as in Regimen A. PBMC are harvested prior to the first APC vaccination
and 1 week after the second, third, and fourth APC vaccinations. PBMC are incubated for 7
days with either peptide the patient was vaccinated with (mutant p53 or ras peptide
fragments) and interleukin-2 (IL-2). The peptide-activated lymphocytes (PAL) are reinfused
over 1 hour 2 weeks after each APC vaccination. Patients receive IL-2 subcutaneously 5 days
a week for 2 weeks beginning 4 hours after each PAL infusion. Patients in both regimens with
stable or responding disease continue treatment every 6 weeks. Patients achieving complete
response continue treatment for up to 1 additional year. Patients are followed at 1 and 2
months.

PROJECTED ACCRUAL: A maximum of 70 patients (5 per Regimen A, 28-65 per Regimen B) will be
accrued for this study.