IGL CAR

IGL CAR (S. Wälchli):

Chimeric Antigen Receptor (CAR) therapy is a promising treatment for cancer. The FDA and the EU approved a commercialized treatment of B-cell malignancies targeting CD19 antigen. However, targeting CD19 can result in B-cell aplasia, which leads to increased susceptibility to infections that can be fatal. Since B cell receptors (BCR) have a bi-allelic restriction of Immunoglobulin (Ig) light chain expression, Ig-Kappa (Igκ) or Ig-Lambda (Igλ), targeting one allele will protect healthy cells from the other. To date only two anti-IGK have been reported (Vera et al. 2006 and Köksal et al. 2019). We have identified the sequence encoding the antigen-binding parts of an anti-Igλ antibody from our collection and designed a second-generation CAR construct (IGL CAR). IGL CAR redirected peripheral blood T cells were tested in various in vitro assays with target cells and compared with the clinical CD19 CAR (clone fmc63). IGL CAR T cells demonstrated specific killing and cytokine release against Igλ+ cells, such as MAVER-1, while no response was detected against Igκ+ cell lines such as BL-41. We are presently developing a combinatorial construct to avoid serum IgL to interfere with IGLCAR-Tc.