Reducing The Adverse Side Effects Of Using Native T-Cells To Destroy Cancer Cells

A Switchable Bispecific T-Cell Nanoengager (sBiTNE) to link T cells with cancer cells that can be reversed if off-tumor toxicity is detected.
Problem:
Compounds which link native T-cells with the surface antigens found on cancer cells have emerged as an effective treatment for blood malignancies and are currently being developed for solid tumors. However, many antigens are not only expressed on cancer cells, but also on healthy tissue, which can result in detrimental and even lethal toxicity when the T cells engage with and destroy healthy cells.
Solution:
This switchable bispecific T-cell Nanoengager (sBiTNE) is not only effective at engaging T-cells to cancer cells to facilitate their destruction, but upon discovery of adverse off-tumor toxicity, a small molecule amantadine (ADM) can be infused to destroy the sBITNEs and limit the damage.
Technology:
The sBiTNE contains regions which bind to CD3, a surface antigen found in T-cells and to HER-2 a surface antigen overexpressed 40 to 100-fold in tumor cells. This links the patient’s native T-cells to tumor cells and facilitates the latter’s destruction. Importantly, if the T-cells have been found to target healthy cells leading to an adverse reaction, the small molecule amantadine (ADM) can be infused which destroys the sBiTNEs, markedly increasing the safety of the treatment.
Advantages:

Engages both T-cells and tumor cells in a dose-dependent manner leading to tumor cell lysis
Binds effectively to CD3 on T-cells and HER-2 on tumor cells
Can be eliminated with introduction of amantadine (ADM), leading to T-cell disengagement, and sizably reduced off-tumor toxicity
Reversibility allows for a higher initial dose of sBiTNEs, leading to more efficient cancer cell destruction while limiting toxicity

Stage of Development:

Target Identified
Preclinical Discovery

A switchable bispecific T cell nanoengager (sBiTNE) for cancer immunotherapy. The sBiTNE engages T cells and tumor cells to induce toxicity to tumor cells effectively. If detrimental off-tumor toxicity is detected, amantadine (ADM) can be infused to destroy the SBiTNEs.
Intellectual Property: