Mechanisms of antigen escape from BCMA- or GPRC5D-targeted immunotherapies in multiple myeloma.

"modeling of wild-type versus p arg27pro mutant bcma using the publicly deposited crystal structure representing the interaction between bcma and j22 9-xi demonstrated that p arg27pro disrupts all contacts between the bcma and the light chain of j22 9-xi (fig 4a ) (protein data bank (pdb) accession no 4zfo ) - .; fig 4 a publicly deposited crystal structure (pdb accession no 4zfo ) by marino et al representing the interaction between wild-type or p arg27pro bcma and j22 9-xi light chain.; human tnfrsf17 cdna sequence was taken from the ccds sequence data available from the national center for biotechnology information (ncbi) ccds database (ccds id: ccds10552 1 ) .; data availability sccnv-seq and scrna-seq datasets are available at the ncbi's gene expression omnibus (which automatically makes a sequence read archive deposit) under the following accession no: gse226336 . for cnv data analysis hdf5 matrices (cnv_data h5) and cn files (node_unmerged_cnv_calls bed) generated by the cellranger-dna suite v 1 1 0 as well as heatmap cn data-generated loupe scdna (v 1 1 0) were processed with customized r scripts (available in the github repository: https://github com/nbahlis/myeloma_immunotherapy_antigen_escape ). supplementary data 1 source data for supplementary fig 2d. data availability sccnv-seq and scrna-seq datasets are available at the ncbi's gene expression omnibus (which automatically makes a sequence read archive deposit) under the following accession no: gse226336"

"for cnv data analysis hdf5 matrices (cnv_data h5) and cn files (node_unmerged_cnv_calls bed) generated by the cellranger-dna suite v 1 1 0 as well as heatmap cn data-generated loupe scdna (v 1 1 0) were processed with customized r scripts (available in the github repository: https://github com/nbahlis/myeloma_immunotherapy_antigen_escape ).; raw scripts to generate sccnv-seq analysis figures included in this paper are available under the github repository ( https://github com/nbahlis/myeloma_immunotherapy_antigen_escape )."

"Competing interests N.J.B. has received research funding from Pfizer and speaker’s bureau honoraria from Amgen, BMS, Sanofi, Pfizer and Janssen; he is a consultant/advisory board member for BMS, Janssen and Pfizer. P.N. received speaker’s bureau honoraria from BMS, Janssen and Sanofi, and is a consultant/advisory board member for BMS and Janssen. C.H. and T.H. have equity ownership of MLL Munich Leukemia Laboratory. O.L. has received research funding from: the National Institutes of Health (NIH), NCI, US Food and Drug Administration, MMRF, International Myeloma Foundation, Leukemia and Lymphoma Society, the Paula and Rodger Riney Myeloma Foundation, Perelman Family Foundation, Rising Tide Foundation, Amgen, Celgene, Janssen, Takeda, Glenmark, Seattle Genetics and Karyopharm; received honoraria and is on advisory boards for Adaptive, Amgen, Binding Site, BMS, Celgene, Cellectis, Glenmark, Janssen, Juno and Pfizer; and serves on independent data monitoring committees for clinical trials led by Takeda, Merck, Janssen and Theradex. J.J.K has received research funding from Amgen, Genentech and Janssen, and has received honoraria and is on advisory boards for Janssen. The other authors declare no competing interests."

"H.L., P.N. and N.J.B. are supported by grants from the Terry Fox Foundation, International Myeloma Society, Myeloma Canada and Leukemia Lymphoma Society of Canada. F.M. and O.L. are supported by the Paula and Rodger Riney Multiple Myeloma Research Program Fund, the Multiple Myeloma Research Foundation (MMRF), the Perelman Family Foundation and a Sylvester Comprehensive Cancer Center National Cancer Institute (NCI) core grant (no. P30 CA 240139). F.M. is supported by the American Society of Hematology. L.R. was supported by the German Cancer Aid and the Paula and Rodger Riney Foundation. J.J.K. and A.K. are supported by the Judy and Bernard Briskin Center for Multiple Myeloma Research at City of Hope, the MMRF and the City of Hope Comprehensive Cancer Center NCI core grant (no. P30 CA 033572). The CoMMpass dataset was generated by the MMRF in collaboration with the Multiple Myeloma Research Consortium."