Kiadis announces pub­li­ca­tion in Blood high­light­ing proof-of-con­cept to enhance poten­cy of anti-CD38 anti­bod­ies with Kiadis’ K-NK004, recent­ly licensed by Sanofi

CD38KO NK cell ther­a­py has the poten­tial to max­i­mize the effi­ca­cy of anti-CD38 against mul­ti­ple myelo­ma

Amsterdam, The Netherlands, July 22, 2020 – Kiadis Pharma N.V. (“Kiadis” or the “Company”) (Euronext Amsterdam and Brussels: KDS), a clin­i­cal stage bio­phar­ma­ceu­ti­cal com­pa­ny devel­op­ing inno­v­a­tive cell ther­a­peu­tics for life-threat­en­ing dis­eases, today announces pub­li­ca­tion of an arti­cle in Blood, Journal of the American Society of Hematology. The arti­cle describes the syn­er­gy of mbIL21 expand­ed NK cells (FC21-NK) mod­i­fied with a CD38 gene knock­out togeth­er with an anti-CD38 mon­o­clon­al anti­body (mAb) for enhanced killing of mul­ti­ple myelo­ma cells.

The pub­li­ca­tion describes the use of the CRISPR/Cas9 sys­tem to delete CD38 (CD38KO) in ex vivo expand­ed periph­er­al blood K-NK cells, with 82% knock out effi­cien­cy. These CD38KO K-NK cells were com­plete­ly resis­tant to anti-CD38 anti­body-induced frat­ri­cide. In addi­tion, as com­pared to wild type NK cells, the CD38KO K-NK cells showed supe­ri­or per­sis­tence in immune defi­cient mice pre-treat­ed with anti-CD38 anti­body, and enhanced ADCC activ­i­ty against CD38-express­ing mul­ti­ple myelo­ma cell lines and pri­ma­ry mul­ti­ple myelo­ma cells. Additionally, analy­sis demon­strat­ed that CD38KO K-NK cells have unique meta­bol­ic repro­gram­ming with high­er mito­chon­dr­i­al res­pi­ra­to­ry capac­i­ty, impor­tant in a hypox­ic tumor micro-envi­ron­ment. Taken togeth­er, these find­ings pro­vide proof-of-con­cept that adop­tive immunother­a­py using ex vivo expand­ed CD38KO K-NK cells has the poten­tial to boost anti-CD38 anti­body activ­i­ty in mul­ti­ple myelo­ma.

Dean Lee, MD, PhD, co-author of the arti­cle, Director of the Cellular Therapy and Cancer Immunology Program at Nationwide Children’s Hospital and The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard Solove Research Institute com­ment­ed, “This work was a great oppor­tu­ni­ty to col­lab­o­rate with Gabriel Ghiaur, MD, PhD, co-author of the arti­cle and Assistant Professor of Oncology at The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University. By com­bin­ing the CRISPR/Cas9 tech­nol­o­gy with the FC21-NK cell plat­form we were able to pro­duce and test an engi­neered NK cell ther­a­peu­tic to address a rec­og­nized hur­dle in immunother­a­py of mul­ti­ple myelo­ma. The ease and effi­cien­cy of this approach increas­es its poten­tial to be trans­lat­ed to the clin­ic.”

Robert Friesen, chief sci­en­tif­ic offi­cer of Kiadis com­ment­ed, “We are excit­ed to see the pub­lished results of this sci­en­tif­ic study, the proof-of-con­cept that tar­get­ed knock­out of CD38 in high­ly stim­u­lat­ed NK cells can be syn­er­gis­ti­cal­ly applied to anti­body treat­ments for the poten­tial ben­e­fit of patients with mul­ti­ple myelo­ma.”

Arthur Lahr, chief exec­u­tive offi­cer of Kiadis, added “This pub­li­ca­tion demon­strates that CD38KO K-NK cells are resis­tant to killing by anti-CD38 anti­bod­ies, and demon­strates how CD38KO K-NK cells improve poten­cy of anti-CD38 anti­bod­ies. This data drove Sanofi’s excite­ment to license KNK004 for com­bi­na­tion with Sarclisa®, to pro­vide bet­ter treat­ment options for mul­ti­ple myelo­ma patients. This data show­cas­es the sci­en­tif­ic ratio­nale under­pin­ning the col­lab­o­ra­tion with Sanofi, and should enhance the under­stand­ing of the poten­tial of this com­bi­na­tion.”

Leave a Reply

Your email address will not be published. Required fields are marked *