There are indeed hybridomas producing anti-CXCR4 mAbs. CXCR4, the chemokine receptor for CXCL12, has recently been involved in the metastatic process of several neoplasms.ou need to have a monoclonal antibody (mAb) against CXCR4 receptor and take the genes encoding variable heavy (VH) and light (VL) to form a scFv-encoding gene and make a construct with CD3ζ and a costimulatory molecule, such as CD28 or 4-1BB (CD137) in order to transfect T-cells, so that you make anti-CXCR4 CAR-T cells. There are indeed out there, in the market and some labs, hybridomas producing anti-CXCR4 antibodies.

CXCR4, is a chemokine receptor for CXCL12, and has recently been demonstrated that it is involved in the metastatic process of several neoplasms, and therefore inhibiting CXCR4 may be of therapeutic value by ablating the metastatic process. However, a main concern exists, as CXCR4 is a receptor expressed on hematopoietic stem cells (interacting through CXCR4 with CXCL12/SDF-1 expressed on stromal cells), CAR-T cells with CXCR4 specificity will expand and propagate in the presence of and cause cytotoxicity to hematopoietic stem cells...!!!

Thank you very much.

T cells also has this CXCR4 receptor on their surface. Studies have shown that binding of CXCL12 ligand in the tumor microenvironment(solid tumors) with the CXCR4 T cell receptor stops T cell binding to the tumor cells. When constructing a car T cells against CXCR4 receptor on tumor cells can we replace the original CXCR4 receptor on the T cell with the CAR? Or we can couple to an antigen recognizing receptor(TCR) only? Please advise on this. Thanks

That is absolutely correct. The CXCR4 receptor is indeed expressed on central memory (CM) T-cells which are important in designing CAR-T cell populations. I have found a paper describing conditional deletion of the CXCR4 receptor (J Immunol., 2014; 193: 1013–1016). I do not know to what extend this can be applied in CXCR4-binding CAR-T's without affecting their functionality...! It has rather to be tested...!!! I hope that this helps !

Thank you so much Christos..

Depending on the technical capacities of your lab, you could try to insert the CAR into the endogenous CXCR4 in T-cells using Crispr/Cas9

Thanks for the answer Klaus,could you please explain it bit more on how you are doing this?

For detailed protocols check the paper Roth et al., Nature 2018

Thanks Klaus