Håkan Mellstedt, M.D., Ph.D. Karolinska University Hospital (Sweden)

NEW ANTIBODIES AND MRD

The tyrosine kinase receptor ROR1 - a potential target for Mab Therapy of CLL

Update:

We have identified a new potential target for CLL therapy - the tyrosine kinase receptor ROR1. During the last year, 13 different mouse monoclonal antibodies against the external part of ROR1 have been produced and tested for specificity and their capability to induce specific cell death of CLL cells.

Three of the antibodies are excellent in inducing a specific leukemia cell death alone (comparable to rituximab but targeting another receptor). The antibodies induce cleavage of the apoptotic protein, PARP, indicating activation of an apoptotic pathway and supporting the produced antibodies in killing the leukemic cells. We have also identified a few small molecule TK inhibitors specific for ROR1 kinase activity.

In summary, three very promising CLL specific antibodies and a few small molecules have been produced which will be further explored and developed with the aim of bringing them to clinical testing for therapy. These unique antibodies and molecules against ROR1 may result in novel targeted therapeutics in CLL.