Gregor B Adams
Chimeric antigen receptor (CAR)-modified T-cell therapies have shown immense promise for the treatment of patients with B-cell malignancies, prompting their exploration across various other blood disorders. These agents have primarily targeted CD19, with 2 currently being evaluated for approval by the FDA for types of non-Hodgkin lymphoma.
Overall, treatment with KITE-585 led to a near eradication of the tumors in the mouse models as compared with untransfused mice. Mice were treated at day 6, when their approximate tumor volume was 100 mm3
. Those in the experimental arm had a rapid decline and elimination of the tumor whereas untreated mice continued to have rapidly growing tumors that eventually surpassed 500 mm3
"When we infuse KITE-585 cells into these animals, we get complete ablation of these tumors cells," Adams said.
CAR T cells were found to be persistent in the study, with an initial spike that plateaued by week 2. The persistence of KITE-585 in the peripheral blood was similar to what was seen with a single copy of the human gene RPP30, showing that there was not a reduction in the cell's ability to proliferate normally.
Following these early preclinical findings, Kite plans to initiate a phase I study to explore the CAR T-cell therapy in patients with multiple myeloma. This study is anticipated to begin enrolling in 2017, according to the company.
- Adams GB, Feng J, Ghogha A, et al. Development of KITE-585: A fully human BCMA CAR T-cell therapy for the treatment of multiple myeloma. In: Proceedings from the 2017 AACR Annual Meeting; Washington DC, April 1-5, 2017. Abstract 4979.
- Adams GB, Feng J, Ghogha A, et al. Selectivity and specificity of engineered T cells expressing KITE‑585, a chimeric antigen receptor targeting B cell maturation antigen (BCMA). In: Proceedings from the 2017 AACR Annual Meeting; Washington DC, April 1-5, 2017. Abstract 2135.
- Rossi J, Paczkowski P, Shen Y-W, et al. Polyfunctional anti-CD19 CAR T cells determined by single-cell multiplex proteomics associated with clinical activity in patients with advanced non-Hodgkin’s lymphoma. In: Proceedings from the 2017 AACR Annual Meeting; April 1-5, 2017; Washington, DC. Abstract 2990.