Indiana Patent of the Month – October 2023

Immunotherapy based on adoptive transfer of lymphocytes into a patient is a valuable therapy in the treatment of cancer and other diseases. One promising avenue of immunotherapy is Chimeric Antigen Receptor T cell (CAR T cell) therapy. This innovative approach utilizes genetically engineered T cells to target specific cancer cells effectively. However, despite its potential, CAR T cell therapy faces challenges like cytokine release syndrome (CRS) and off-target toxicity.

Endocyte, Inc., which was acquired by Novartis in 2018 and remains a prominent figure in the field of cancer research, has introduced a novel method to enhance the precision and safety of CAR T cell therapy. Their approach involves a compound comprising a folate linked to fluorescein isothiocyanate (FITC), which is administered to the patient. This compound serves as a bridge between cancer cells and CAR T cells, facilitating targeted treatment.

The treatment begins with the administration of a compound that includes a small molecule ligand linked to a targeting moiety by a linker. This compound specifically binds to cancer cells, minimizing off-target effects.

Next, a composition of CAR T cells is administered to the patient. These CAR T cells have a unique chimeric antigen receptor (CAR) designed to recognize the targeting moiety present in the compound. This recognition is crucial for directing the CAR T cells to the cancer cells.

To address the challenge of CRS, a rescue agent comprising fluoresceinamine, FITC, or fluorescein (or their salted forms) is administered to the patient. This rescue agent helps prevent or reduce cytokine release syndrome, a potentially life-threatening side effect of CAR T cell therapy.

The method specifically targets folate receptor-expressing cancers, offering a tailored approach to treatment. By controlling CAR T cell activation and minimizing off-target effects, this approach promises a more effective and safer treatment for cancer patients.

The treatment can be adapted based on the patient’s condition. For instance, if the patient shows signs of CRS before step three, the rescue agent can be administered to reduce its severity. The method is designed to decrease tumor volume, contributing to better treatment outcomes.

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