PROSTATE CANCER VACCINE BY SUPPRESSING Ii PROTEIN
DESCRIPTION: Suppressing the Ii protein by anti-sense oligonucleotides in MHC
class Il-positive cancer cells creates a potent cancer cell vaccine.
Presumably, additional determinants which are normally excluded in the ER by
the Ii protein from the MHC class II antigenic peptide binding site, stimulate
a potent and long lasting T helper cell response which guarantees (through
dendritic cell 'licensing') a tumor-clearing T killer cell response. We have
proved this point in two murine cancer models and identified the most active
lead drug. We now focus on prostate cancer because there are no life savings
therapies once tumor recurs in patients with an otherwise healthy immune
system. Adequate tumor is available in 50 percent of patients at primary
resection, and in all early during recurrence. Tumor is also then accessible to
injection in situ with liposomes and immunoliposomes containing the lead drug.
First, we have begun to validate Ii protein suppression methods in human
prostate cancer cell lines (in anticipation of preparing cancer cell vaccines
under Phase II). Second, we will optimize cell vaccine dose and dosing schedule
in the murine RM-9 prostate cancer model, as we have done in two previous
murine tumor models. Third, we will use the optimized cell vaccine regimen plus
GM-CSF (and subsequently lL-2) to treat mice with established subcutaneous and
orthotopic RM-9 tumors. Subsequent studies in Phase II will focus on the use of
fresh human tissues, the inclusion of radiation in the treatment of advanced
RM-9 tumors and a pre-IND conference with the FDA.
PROPOSED COMMERCIAL APPLICATION:
Tumor cell vaccine for prostate, breast, ovarian and colon cancer. In situ
immunotherapy of metastates enhancement or dendritic cell immunotherapies
Small Business Information at Submission:
Principal Investigator:Robert E. Humphreys
ANTIGEN EXPRESS, INC.
1 INNOVATION DR WORCESTER, MA 01605
Number of Employees: