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Antibody therapies

Antibody coating cancer cells.PNG

A cancer-targeting antibody (green) binding to the surface of malignant T cells. The lysosomes are shown as red and nucleus shown as blue.  

image credit: Paul Lab, Johns Hopkins University

Cancer-targeting antibodies are designed to specifically recognize and attack cancer cells while sparing healthy ones. These antibodies are engineered to target unique surface markers or antigens present on cancer cells. By binding to these markers, cancer-targeting antibodies can trigger various anti-tumor mechanisms, such as immune system activation (e.g. Bispecific antibodies),  and delivery of a toxic payload (e.g. Antibody-drug conjugates or ADCs) into the cancer cell, resulting in cancer cell death. As research and development in this field continue to advance, cancer-targeting antibodies hold the promise of revolutionizing cancer treatment and improving the lives of patients worldwide. Our cancer-targeting antibodies utilize the format of bispecific antibodies and ADCs to kill the cancer cells. 

Bispecific antibodies (BsAbs)

Bispecific antibodies are engineered to simultaneously bind two different antigens. This is unlike the traditional monoclonal/monospecific antibodies that bind to a single antigen. This unique characteristic enables bispecific antibodies to bridge immune cells such as T cells, directing them towards a specific target cell such as a cancer cells. 

Thus bispecific antibodies help activate the T cells and enhance their ability to recognize and eliminate cancer cells. As research and technology in this field advance, bispecific antibodies are likely to play a pivotal role in shaping the future of precision medicine.

 

 

Antibody drug conjugates (ADCs)

An ADC combines the specificity of antibodies with the potency of cytotoxic drugs. ADCs are designed to selectively target cancer cells while minimizing damage to healthy tissues. The structure of an ADC typically consists of two components: a monoclonal antibody that recognizes a specific antigen on cancer cells and the cytotoxic drug, which is a potent cell-killing agent.

 

 

 

 

Once the ADC binds to the cancer cell's surface antigen, it is internalized, and the cytotoxic drug is released inside the cell, leading to its destruction. This targeted approach allows for higher concentrations of the cytotoxic drug to be delivered directly to cancer cells, improving the efficacy of treatment while reducing systemic toxicity. As research advances, the development of more sophisticated ADCs holds the potential to revolutionize cancer treatment and improve patient outcomes even further.

 

Watch antibodies enter cancer cells

We use ADCs to deliver drugs inside cancer cells. Our live cell imaging method allows us to track the antibody entering cancer cells. The cancer-targeting antibody is attached to a dye that emits red fluorescence under acidic pH. When the antibody is added to a culture of cancer cells, the antibody is endocytosed into the lysosome within the cancer cells. The acidic pH inside the lysosome induces the antibody to emit red fluorescence and the cancer cells turn red over time. 

video credit: Paul Lab, Johns Hopkins University

Read about our work on antibody therapies:

Cancer therapy with antibodies

Nature Reviews Cancer, accepted 2024 

TRBC1-targeting antibody-drug conjugate for the treatment of T-cell cancer

Nature, 2024

Hydrophobic interactions dominate the recognition of a KRAS G12V neoantigen

Nature Communications, 2023 

TCR β chain–directed bispecific antibodies for the treatment of T cell cancers

Science Translational Medicine, 2021

Targeting a neoantigen derived from a common TP53 mutation

Science, 2021

Bispecific antibodies targeting mutant RAS neoantigens

Science Immunology, 2021

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