- VANUDIS - Biotech Company
- SkyAngle Building
- Max-Jarecki-Str. 21
- 69115 Heidelberg
- office@vanudis.net
- +49 6221 3919 0
CAR-T cell therapeutics
Development of highly effective and well tolerable cell therapeutics
Antigen escape mechanisms, such as antigen-loss and downregulation of cell-surface densities, have emerged as major issues limiting the efficacy and durability of CAR-T cell therapy. Relapses due to the outgrowth of antigen-low tumor cells after high initial response rates have been observed in multiple clinical studies, for example using anti-CD22 and anti-BCMA CAR-T cells. Antigen-low escape may be an even greater barrier to success in solid tumors, which show greater heterogeneity in target antigen expression compared to hematological tumors.
Current CAR-T cell therapeutics show limited efficacy when the specific target antigen recognized by the CAR is expressed at low densities, i.e. a few thousands of molecules per cell. Initially, tumor cells often express high amounts of tumor-associated antigens, but under the pressure of the therapeutic intervention, tumor cells frequently downregulate the amount of the target antigen expressed on their surface, resulting in the inability of CARs to sufficiently activate T cells and subsequent killing of tumor cells.
At VANUDIS, we developed a technology platform for generating CAR-T cell products being capable of destroying tumor target cells with even ultralow target antigen densities, i.e. less than 100 molecules per cell, which are far below the activation limit for current CAR-T cell therapeutics. Human T cells expressing this novel CAR system have a boosted capacity to induce signaling, proliferation and persistence in response to antigen binding, thereby providing the basis for significantly improved long-term efficacy in patients with lower rates of relapses because of reduced antigen expression on tumor cells.
In our endeavor to improve treatment outcomes for cancer patients, we further explore new CAR cell entities by developing novel CAR-NK and CAR-Macrophage therapeutics to overcome current limitations of CAR-T cells especially for the treatment of solid tumors.