CD37 CAR

CD37 CAR (S. Wälchli/B. Caulier):

We design novel CARs that target B-cell malignancies. CD37 is a tetraspanin that is widely expressed on the surface of mature B cells. Due to its high level expression across all subtypes of B-cell non-Hodgkin lymphoma (B-cell NHL), CD37 is one of many potential antibody targets for B-cell malignancies. Since adoptive immunotherapy using CAR gene-modified T-cells has generated impressive clinical responses in B-cell malignancies, we designed a novel second-generation CAR that redirects T-cell specificity towards CD37. Initial testing showed that CD37-directed human peripheral blood CAR T cells potently killed CD37⁺ B-cell NHL cell lines such as SU-DHL-4, BL-41, Mino and U-2932. We compared the anti-lymphoma activity of CD37-specific CAR T cells with that of CD19-specific CAR T cells and found no difference except for U-2932 cells which were more susceptible to CD37-specific CAR T cells, in concordance with high CD37 expression and low CD19 expression in these cells. The cell line U-2932 was originally derived from a patient with ABC-type of diffuse large B-cell lymphoma (DLBCL), who suffered from many relapses after multiple chemo- and radiotherapy regimens. Assessment of expression of CD19 and CD37 as well as other B-cell antigens such as CD20, CD22 and CD23 demonstrated a dramatic variation in their expression across the B-cell NHL cell lines. Genetic heterogeneity is common in B-cell NHLs and loss of or reduced expression of CD19 has already been reported in some B-cell NHLs. Moreover, extensive chemo- and radiotherapy regimens could potentially contribute to the loss of or reduced CD19 expression. Therefore, we are now in the process of screening B-cell NHL patient tumors for loss of or reduced expression of particular B-cell antigens, including CD19, CD20 and CD37.  This type of screening can help us to identify the patient groups that are likely to benefit from CD19-, CD20- or CD37-targeted therapies. In summary, our findings suggest that CD37-directed CAR T cells can be used as an alternative to CD19-targeted CAR T cells, especially when CD19 expression is lost or reduced in patients’ tumor cells.

If you want to learn more about our CAR CD37 and its potential commercial applications, make sure to visit our Technical Transfer Office INVEN2 as well as this short presentation.