5th World Congress on Cancer Therapy
North Shore University Hospital, USA
Title: Monoclonal antibodies that target pancreatic and colorectal cancer for both diagnosis and therapy
Biography: Myron Arlen
The use of monoclonal antibodies has become an important aspect in planning for the treatment of the cancer patient and in particular those with metastatic pancreatic and colorectal cancer. It does require that the antibody be specifi c for an immunogenic target in the tumor cell. In the overall scheme, such an antibody should fi t into Lee Hartwells (Fred Hutchinson Cancer Center) description of a product (mAb) that can both detect specifi c tumor proteins with a high degree of accuracy for diagnosis and when confi rmed, be used as a therapeutic agent to target and destroy the malignancy. Antibodies for a large array of neoplasms are now in development at Precision Biologics. All are based on having been able to defi ne the immunogenic protein expressed by the tumor. Such proteins have been now been characterized for Pancreatic and Colon Cancer. Th ey have been shown in most instances to be oncofetal in origin. Th e primary immunogen, seen for the most part in both tumors, appears to be a post translational modifi cation of MUC5ac. Th e gene is turned on in thr fetus to produce needed intestinal mucin, and later prior to full fetal matur\\\\ation, the gene is remethylated. Failure to shut down this process induces the appearance of cytic fi brosis. In the adult, an oncogenic transformation modifi es the MUC5ac gene and the protein that is expressed, induces malignant transformation. Th e protein that is expressed as TAA, appears in the earliest phases of transformation to malignancy acting as a target for immunogenic diagnosis and therapeutic targeting. Th roughout progression of the lesion to the metastatic state, this TAA is not modifi ed and as such, that antibody targeting the primary tumor remains eff ective in addressing the metastatic lesion. In treating pancreatic and colorectal Ca we have shown that when the specifi c TAA is employed, enhancement in immune reactivity is essentially mediated via the humoral immune system. Cell mediated immunity takes a minor position. Th e antibody that we have employed for identifying the tumor target, that is Neo 102, has been shown to not only have a high rate of ADCC but induces apoptosis secondary to favtors defi ned by Annexin V binding. In our treatment of metastatic pancreatic cancer patients having failed Gemcitabine therapy, the addition of Abraxane has been shown to increase survival by approximately 8 wks. When monoclonal Neo 102 is delivered IV following Gemcitabine failure the average improvement in survival is approximately 26-30 wks. Realizing that many immunotherapeutic agents require removal or diminution of inhibitory serum factors that can be eff ected by chemotherapy, . new studies are being initiated. Th ese have been designed to compare Gemzar Abraxane vs. Gemzar Abraxane plus monolonal antibody (Neo 102). Later we will be initiating studies where patients have undergone surgery for pancreatic Ca. Following the eff ective removal of a primary pancreatic Ca by the Whipple procedure, the recurrence rate by 2 years post surgery can reach more than 90%. We have designed a peptide vaccine using the eiptope binding site defi ned by Phage Display which targets the mutated MUC5ac protein. Th e study is designed to provide vaccine one month post surgery and it is hoped to illustrate that the vaccine which produces the needed level of antibody by 4-6 months can prevent the high rate of recurrence that has been noted.