A prominent research team from the University of Pittsburgh Center for Antibody Therapeutics has identified a wide range of fully human antibodies and antibody domains with the potential to treat a vast array of human cancers and other diseases.
Description
A prominent research team from the University of Pittsburgh Center for Antibody Therapeutics has identified a wide range of fully human antibodies and antibody domains with the potential to treat a vast array of human cancers and other diseases. The use of antibodies, including antigen binding fragments (Fabs), single-chain variable fragments (scFvs) and single domain antibodies (VHs) 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 bispecific antibodies immune cell engagers), T cells and NK cells can be recruited 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 antibody domains promoting T cell recognition of diseased cells, leading to an immune response and associated cell death.
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):
Cancers:
• Acute lymphoblastic leukemia
• Brain cancer
• Breast cancers
• Chronic and acute myeloid leukemias
• Colorectal cancer
• Ewing’s sarcoma
• Gastric adenocarcinoma
• Glioblastoma
• Lung cancers
• Mesothelioma
• Neuroblastoma
• Osteosarcoma
• Ovarian cancers
• Pediatric medulloblastoma
• Pancreatic cancer
• Prostate cancer
• Renal cell carcinoma
• Rhabdomyosarcoma
• Squamous cell cancer of the head and neck
• Urothelial cell carcinoma
Infectious Diseases:
• Acute Respiratory Distress
• HIV
Neurodegenerative diseases:
• Alzheimer’s disease
• Parkinson’s disease
Advantages
• Unlike many antibodies currently being investigated, which are mice derived, all novel antibodies and domains presented here are fully human, thereby reducing safety concerns around immunogenicity as seen in mice-derived antibodies. Additionally, many of these novel antibodies (and domains) are the first human antibodies in their class ever identified.
• Proteins targeted with these antibodies and domains are over-expressed in diseased cells and either not expressed, or expressed at negligible levels in healthy tissue, allowing for selective targeting of diseased cells and reducing the risk of side effects. Many of the novel antibody domains were developed for the same target but different epitopes, further enhancing the specificity and allowing for combination therapy. Some target proteins are found in the tumor microenvironment and are linked to angiogenesis and metastasis. The use of antibodies and domains has the potential to inhibit the spread of diseased cells to other parts of the body, further improving patient outcomes.
• These novel antibodies have been 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. Additionally, some domains presented here are engineered antibody domains (eAd), based on IgG heavy chain variable domain, with the potential to be further engineered to optimize efficacy, or modified to form other therapeutic approaches including antibody drug conjugates (ADCs), bispecific killer cell engager (BiKE) and bispecific T cell engager (BiTE), enhancing the uses for these Fabs.
• It has been demonstrated how the use of the CAR approach to modify T cells can lead to direct targeting of diseased cells, an approach used successfully in other immunotherapeutic treatments.
• These novel antibody fragments have much lower molecular weight than some traditionally used mouse-derived human monoclonal antibodies, often only 1/10th of full antibodies. This is likely to lead to better tumor penetration, further improving patient outcomes.
• These novel antibody domains 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 antibody domains developed within the University of Pittsburgh have been tested in vitro and shown to be effective against the targeted cancer cells. The results highlight the potential of these antibodies for further progression to in vivo and human studies.
Antibodies targeting the following, IL1RAP, FGFR4, CD135, PSCA, PRTG, and FST, have all undergone in vivo testing successfully.
IP Status
https://patents.google.com/patent/WO2024108163A2
