A prominent research team from the University of Pittsburgh Center for Antibody Therapeutics have identified a wide range of fully human antibodies and antigen binding fragments (Fabs) with the potential to treat a vast array of human cancers and other diseases.
Description
The use of antibodies, including Fabs, as a therapeutic approach for cancers and viruses is a growing area of interest. The therapeutic benefits come from several mechanisms of action.
One approach is through identification of key proteins overexpressed by individual cancers; antibodies can be designed to specifically target these key proteins, disrupting the life cycle of the diseased cells, reducing cell proliferation, or leading to cell death.
Another mechanism uses antibodies to target surface proteins on cells as a carrier for drug compounds specific to cancer or virus cells – antibody drug conjugates. A third approach where tailored antibodies can lead to cell death is through initiation of a patient’s immune response to the diseased cell. Using bivalent antibodies (Fabs), T cells can bind to previous immune evading cells and promote an immune response leading to cell death.
Additional research on some of these novel antibodies demonstrated how chimeric antigen receptor (CAR)-modified T cells express some of these antibodies promoting T cell recognition of diseased cells, leading to an immune response and associated cell death.
The innovations presented here are a series of antibodies designed to target individual cancer and virus cells to provide personalized treatment to cancer patients, improving outcomes.
Applications
The novel human antibodies, or Fabs, presented here have the potential to be used in the treatment of the following conditions (not an exhaustive list):
· Acute lymphoblastic leukemia
· Mesothelioma
· Acute Respiratory Distress
· Neuroblastoma
· Alzheimer’s disease
· Osteosarcoma
· Brain cancer
· Ovarian cancers
· Breast cancers
· Pediatric medulloblastoma
· Chronic and acute myeloid leukemias
· Pancreatic cancer
· Colorectal cancer
· Parkinson’s disease
· Diffuse intrinsic pontine glioma
· Prostate cancer
· Ewing’s sarcoma
· Renal cell carcinoma
· Gastric adenocarcinoma
· Rhabdomyosarcoma
· Glioblastoma
· Squamous cell cancer of the head and neck
· HIV
· Urothelial cell carcinoma
· Lung cancers
Advantages
• Fully human, unlike mice derived Fabs currently being investigated reducing immunogenicity risk.
• Highly selective to diseased cells or surround environments, reducing risk of side effects.
• Identified through a comprehensive discovery technique that could be easily applied to other identifiable targets, allowing for efficient discovery of treatment for a wide variety of conditions.
• Antibodies can be engineered to specific targets and efficacy can be enhanced through incorporation into other therapeutic approaches, including antibody drug conjugates, bispecific killer cell engager (BiKE), bispecific T-cell engager (BiTE) and CAR-modified T cells to initiate immunotherapy.
• These novel Fabs have much lower molecular weight than some traditionally used antibodies, likely to lead to better tumor penetration, further improving patient outcomes.
• These novel Fabs have been found to be stable at body temperature, reducing the risk of aggregation previously observed with some earlier developed antibodies.
Invention Readiness
All the novel Fabs developed within the University of Pittsburgh have been tested in vitro and shown to be affective against the targeted cancer cells, highlighting the potential of these antibodies to be further developed and progressed to in vivo and human studies.
One Fab, targeting follistatin is currently undergoing in vivo analysis.
IP Status
https://patents.google.com/patent/US20240417485A1
