The purpose of this study is assess the safety of administering repeated doses of IMF-001, a vaccine, to patients with solid tumors that express NY-ESO-1 antigen. If the vaccine is therapeutically useful, a second goal is to establish the maximum therapeutic dose to treat patients with NY-ESO-1 positive cancers.
NY-ESO-1 was isolated by serological analysis of recombinant cDNA expression libraries (SEREX), using tumor mRNA and autologous serum from an esophageal cancer patient. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that NY-ESO-1 displayed the typical expression pattern of cancer testis antigens (CT antigens). NY-ESO-1 mRNA was expressed only in testis of normal tissues tested and in various types of cancer, including lung cancer, breast cancer, malignant melanoma and bladder cancer. Since testis is an immune privileged organ where HLA molecules are not expressed, these antigens can be considered tumor-specific. IMF-001 is a CHP-NY-ESO-1 complex consisting of recombinant NY-ESO-1 protein and cholesteryl hydrophobized pullulan (CHP). CHP forms colloidally stable nanoparticles in water and complexes with substrate such as NY-ESO-1 protein. It is well known that exogenous antigen proteins can induce specific CD4+ T cells but not specific CD8+ T cell. Dendritic cells pulsed with IMF-001 induced NY-ESO-1 specific CD8+ T cells in blood samples of 4 healthy volunteers. These data suggest that immunization of patients with IMF-001 can evoke not only specific CD4+ T cells responses but also specific CD8+ T cell response to NY-ESO-1 more effectively than NY-ESO-1 protein alone. Similar results for both cellular and humoral immunity in response to NY-ESO-1 protein were observed in previous clinical investigational studies with IMF-001.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
23
subcutaneous injection of fixed dose IMF-001 (100 or 200 mcg) every 2 weeks.
Roswell Park Cancer Institute
Buffalo, New York, United States
New York University (NYU) Cancer Center
New York, New York, United States
Number of patients with adverse events as a measure of safety and tolerability of repeat doses.
Time frame: Date of first dose until 30 days after off-study, or until resolution of related AEs
Tumor response using RECIST 1.1
Scans will be performed each cycle after the 4th and 6th injections (approximately Weeks 7 and 11). Scans will be performed; or, for patients with prostate cancer, response will be based on PSA levels.
Time frame: Each cycle at weeks 7 and 11 (appx.)
Humoral and cellular immune response as indication of IMF-001 biologic activity
Humoral response (NY-ESO-1 antibody titre) Cellular response (NY-ESO-1 specific CD4 and CD8 T-cells)
Time frame: Starting from first dose, samples taken within 72hrs of the 1st, 3rd, and 5th doses of each cycle until off-study
Optimal dose based on number of patients with adverse events at that dose
Time frame: Date of first dose until 30 days after off-study, or until resolution of related AEs
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