Invented by David Scheinberg, Tao Dao, Cheng Liu, Su Yan, Memorial Sloan Kettering Cancer Center, Eureka Therapeutics Inc

The Market Potential of T-cell Receptor-Like Antibodies Specific for a WTI Peptide Presented to HLA-A2 In recent years, there has been a significant surge in the development of immunotherapies for various diseases, particularly cancer. Among these, T-cell receptor (TCR)-like antibodies have emerged as a promising avenue for targeted therapies. Specifically, TCR-like antibodies that are specific for a WTI peptide presented to HLA-A2 have shown great potential in the field of cancer immunotherapy. This article explores the market potential of these antibodies and their implications for the future of personalized medicine. To understand the market potential, it is crucial to first comprehend the significance of TCR-like antibodies specific for a WTI peptide presented to HLA-A2. HLA-A2 is a major histocompatibility complex (MHC) class I molecule that plays a critical role in presenting antigens to cytotoxic T cells. The WTI peptide, derived from a tumor-associated antigen, is presented by HLA-A2 on the surface of cancer cells. TCR-like antibodies that specifically recognize this complex can effectively target and eliminate cancer cells, making them a valuable tool in cancer immunotherapy. The market for TCR-like antibodies specific for a WTI peptide presented to HLA-A2 is primarily driven by the increasing prevalence of cancer worldwide. According to the World Health Organization (WHO), cancer is one of the leading causes of death globally, with an estimated 9.6 million deaths in 2018 alone. Traditional cancer treatments, such as chemotherapy and radiation therapy, often have limited efficacy and can cause severe side effects. Therefore, there is a growing demand for more targeted and personalized therapies that can effectively combat cancer while minimizing adverse effects. TCR-like antibodies offer several advantages over traditional therapies. Firstly, they can specifically recognize and bind to cancer cells presenting the WTI peptide-HLA-A2 complex, leading to targeted destruction of cancer cells while sparing healthy cells. This selectivity reduces the risk of off-target effects and enhances the overall safety profile of the therapy. Secondly, TCR-like antibodies can be engineered to have increased affinity and potency, further improving their therapeutic potential. Additionally, these antibodies can be combined with other immunotherapies, such as immune checkpoint inhibitors, to enhance their efficacy. The market potential of TCR-like antibodies specific for a WTI peptide presented to HLA-A2 is further bolstered by advancements in antibody engineering and manufacturing technologies. The development of novel antibody formats, such as bispecific antibodies and antibody-drug conjugates, has expanded the therapeutic possibilities of these antibodies. Furthermore, improvements in antibody production processes, such as cell line development and purification techniques, have increased the scalability and cost-effectiveness of manufacturing these antibodies. However, there are several challenges that need to be addressed for the successful commercialization of TCR-like antibodies specific for a WTI peptide presented to HLA-A2. One of the major hurdles is the identification and validation of suitable WTI peptides that are presented by HLA-A2 in various cancer types. Additionally, the complex nature of TCR-like antibody development and the need for personalized medicine approaches pose logistical and regulatory challenges. Overcoming these obstacles will require collaboration between academia, industry, and regulatory bodies to streamline the development and approval processes. In conclusion, the market potential of TCR-like antibodies specific for a WTI peptide presented to HLA-A2 is significant, driven by the increasing prevalence of cancer and the need for more targeted and personalized therapies. These antibodies offer a promising avenue for cancer immunotherapy, with the potential to revolutionize the treatment landscape. However, further research, development, and collaboration are essential to overcome the challenges associated with their commercialization. With continued advancements in antibody engineering and manufacturing technologies, TCR-like antibodies specific for a WTI peptide presented to HLA-A2 have the potential to transform the field of personalized medicine and improve patient outcomes.

The Memorial Sloan Kettering Cancer Center, Eureka Therapeutics Inc invention works as follows

The present invention provides antigen-binding proteins that specifically bind Wilms tumor protein (WT1) including humanized, fully human and chimeric antibodies against WT1, as well as antibody fragments, CARs, fusion proteins and conjugates thereof. These antigen-binding proteins and antibodies bind HLA-A0201 restricted WT1 peptide. These antibodies, fragments and fusion proteins, as well as conjugates, are useful in the treatment of WT1-associated cancers. For example, breast, prostate, ovarian, and multiple myeloma cancers. Anti-WT1/A antibody may include one or more amino acid substitutions in the framework region to enhance protein stability, binding, and/or expression.

Background for T-cell receptor-like antibodies that are specific for a WTI peptide presented to hla-a2

Selecting High Affinity ScFV against a WT1 peptide

Materials

Methods

Engineering full length mAb using the selected ScFv fragments.

Example 1

Selection for ScFv Specific to WT1p/A2 complex Using a Fully Human Phage Library.

Example 2

Generation Of Full-Length Human IgG1.

Example 3

Specificity and binding avidity of IgG1 mAb

Binding Human Cell Lines.

Example 4

Epitope Mapping.

Example 5

Quantitation of WT1 Ab1 Binding sites on Cells.

Example 6

WT1 ab1 Binding Leukemic Samples.

Example 7

WT1 mediates ADCC against tumor cells

Example 8

WT1 AB1 eliminates human leukemia cells in NSG mice

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