Gregory P. Adams, PhD
Office Phone: 215-728-4342
Developing Antibodies for the Treatment of Breast and Ovarian CancerKim Boland, Tatiana (Tanya) Karakasheva, Calvin Shaller & Heidi SimonsA Novel, Bispecific Antibody's path from the Lab to clinic This content requires the Adobe Flash Player.
Video: Learn more about the origins of bispecific antibody
research at Fox Chase with Dr. Gregory Adams
and Dr. Matthew Robinson (6 minutes).
For a number of years my group has focused on developing and optimizing antibodies that target the EGFR family of transmembrane proteins, composed of HER2 (HER2/neu or ErbB-2), HER3 (ErbB-3), HER4 (ErbB-4) and EGFR. The members of this growth factor receptor family are overexpressed in a large variety of carcinomas and are often correlated with a poor prognosis. We have created a bispecific scFv molecule, ALM that co-targets HER2 and HER3, leading to selective accumulation in tumors and growth inhibition. This approach was patented and licensed to Merrimack Pharmaceuticals and a modified version of ALM, MM111, is currently in clinical trials at FCCC. We are developing antibody-based agents to target the Müllerian Inhibiting Substance Type II Receptor (MISIIR). MISIIR plays a critical role in the regression of the female reproductive tract in males during fetal development, is expressed on the surface of human ovarian cancer, breast cancer and prostate cancer cells and primary human ovarian cancer cells have been found by others to apoptose in response to treatment with the Müllerian inhibiting substance (MIS). We have produced recombinant MISIIR and have used it to isolate scFv molecules from naïve phage display libraries that specifically target this receptor. We are currently evaluating anti-MISIIR immunoconjugates for in vivo efficacy in mouse models of human ovarian cancer.Top
ImmunoPET Detection of CancerCalvin Shaller, in collaboration with Matthew Robinson
While PET imaging with 18FDG has become commonplace in the diagnosis of patients with cancer, many types of tumors (e.g., Prostate cancer) are not FDG-avid. Recent efforts to develop antibody-based targeting strategies for PET isotopes have been limited due to the short physical half-life of the commonly available PET isotopes (e.g., F-18) and unacceptable retention of the radioisotopes (e.g., Cu-64 and I-124) in the kidneys and liver. To address this, we are employing engineered antibody fragments to specifically deliver PET radioisotopes to tumors. Our lead agent is a non-covalent dimeric single-chain Fv molecule known as the C6.5 Diabody that exhibits first pass renal elimination leading to highly selective tumor localization and minimal retention in normal tissues. We have demonstrated extremely promising tumor targeting in preclinical models and are actively pursuing clinical development of the C6.5 Diabody.Top
AffinityStephen Rudnick, Benjamin Roberts & Kim Boland
Therapeutic antibodies are typically engineered to have the highest possible binding affinity with KD’s in the low nanomolar to picomolar range. However, extremely high affinity has been found to hinder antibody penetration into tumors and promote internalization and catabolism of the antibodies by perivasular tumor cells, potentially limiting their therapeutic efficacy. We are systemically evaluating panels of anti-HER2 and anti-EGFR IgG molecules spanning a wide range of affinity for a given target epitope in immunodeficiant and transgenic mice (expressing human HER2 or human EGFR) with the goal of determining the impact of affinity and antigen expression on normal tissues on tumor targeting, penetration and therapeutic efficacy.
NanobiosensorsLina Loo, in collaboration with Hossein Borghaei
The ability of clinicians to use proteins and cells that are present at low copy numbers in biological samples (e.g., serum) to detect early stage cancer and assess immune activation resulting from novel treatments has been limited by the insensitivity of currently available detection methodologies such as ELISA and ELISPOT assays. The recent development of extremely sensitive piezoelectric cantilever sensors offers the potential to identify the presence of extremely rare proteins at picomolar concentrations and single clones of antigen-specific immune effector cells. We are working with colleagues at Drexel University (Drs. Wei and Wan Shih), Temple University (Dr. Eric Borguet) and the Nanotechnology Institute in Philadelphia to develop antibody/piezoelectric cantilever biosensors and validate their efficacy on blood samples from cancer patients and healthy donors.Top