- Ramona Bhattacharya
The chemokine receptor, CCR4 is a seven transmembrane G protein-coupled cell surface receptor molecule with selective expression on cells of the hematopoietic system. In adult T cell leukemia (ATL), the cell-surface expression of CCR4 on leukemic cells has been found to be nearly universal. Therefore, a CCR4-directed chimeric antigen receptor (CAR) -cell may provide an effective therapeutic against ATL.
Researchers at the National Cancer Institute (NCI), Lymphoid Malignancies Branch, developed a lentivirus-derived CAR against the CCR4 molecule. The CAR can be directed to either genetically modified autologous or to allogeneic T or natural killer (NK) -cells to develop the ATL therapy. This technology includes a method of identifying lymphoid or solid tumors that produce CCR4 mRNA and then utilizing CD3+ T cells and/or NK cells to generate genetically modified T cells and/or NK cells (autologous or allogeneic) that express the CCR4 directed CAR. The identified malignancy can then be treated with the infusion of genetically modified T/NK cells.
The NCI seeks licensing and/or co-development of an adoptive cellular therapeutic modality that targets CCR4, which is overexpressed in certain lymphoid malignancies as well as solid tumors.
- Identification and treatment of CCR4 mRNA producing lymphoid or solid neoplasms
- CCR4 putative biomarker in lung adenocarcinoma and other cancers
- CCR4 is a more recent target for cell-based immunotherapy
- Allogenic NK cells would enable wider use of cell-based therapies
Liyanage P. Perera Ph.D. (NCI), Thomas A. Waldmann M.D. (NCI), Kevin C. Conlon M.D. (NCI), Pin-Yu Perera DVM, HCLD
- Discovery (Lead Identification)
Perera, LP, et al. Chimeric antigen receptor modified T cells that target chemokine receptor CCR4 as a therapeutic modality for T-cell malignancies. [PMID 28543380]
- PCT: PCT Application Number PCT/US2017/052437, Filed 20 Mar 2019
- Foreign Filed: - Patent Application 17778069.9, Filed 20 Sep 2017
- Foreign Filed: - Patent Application 2017332161, Filed 10 Sep 2017
- Foreign Filed: - Patent Application 3037518, Filed 20 Sep 2017
- U.S. Patent Filed: U.S. Patent Application Number 16/334,724, Filed 19 Mar 2019