Session: 711. Cell Collection and Manufacturing of HSPCs, CAR-T Cells, and Other Cellular Therapy Products: Poster II
Hematology Disease Topics & Pathways:
Fundamental Science, Research
Methods: Using a bicistronic lentiviral vector and healthy human donor T cells, we generated rapid manufactured anti-CD19/CD20 CAR-T cells (KITE-753). The bicistronic lentiviral vector encodes for an anti-CD19 CAR, containing the FMC63 binder and CD28 costimulatory domain, and anti-CD20 CAR, containing a novel CD20 binder and 41BB costimulatory domain. Anti-CD19/CD20 CAR-T cells manufactured in a more traditional process (KITE-363) served as the benchmark comparator. The final products were characterized via immunophenotyping and functionally assessed in vitro and in vivo.
Results: KITE-753 exhibited high expression of both CARs and increased proportion of juvenile T cells compared to the KITE-363 benchmark. In vitro, both CAR-T products produced cytokines, upregulated activation markers and proliferated in response to antigen-positive target cells. However, KITE-753 showed a higher frequency of activated cells and greater antigen-dependent proliferation compared to the KITE-363 benchmark. In an in vivo disseminated tumor model of B-cell acute lymphoblastic leukemia (Nalm6 tumor cell line), KITE-753 demonstrated antitumor activity at a dose more than 25-fold lower than that of the KITE-363 benchmark. Moreover, KITE-753 expansion in the peripheral blood of mice was more than 5-fold higher compared to the KITE-363 benchmark.
Conclusion: The results of these preclinical studies of KITE-753 highlight that rapid manufacturing enriches for a more juvenile, less differentiated T-cell population, resulting in superior antitumor efficacy and potency with enhanced CAR-T expansion. In addition to the potential to prevent and rescue CD19 negative relapses, the improved product potency of the rapid manufactured KITE-753 may enable the use of lower CAR-T doses in the clinic. A Phase 1, first-in-human, open-label, multicenter study is currently ongoing to evaluate the safety and efficacy of KITE-753 in patients with relapsed/refractory B-cell lymphomas (NCT04989803).
Disclosures: Murakami: Kite, a Gilead company: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties. Guevara: Kite, a Gilead company: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties; Astellas: Patents & Royalties. Cai: Kite, a Gilead company: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties. Tsai: Kite, a Gilead company: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties. Banerjee: Kite, a Gilead company: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties. Ou: Kite, a Gilead company: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties. Yoder: Kite, a Gilead company: Current Employment, Current equity holder in publicly-traded company. Viaud: Calibr: Patents & Royalties; Gustave Roussy Institute: Patents & Royalties; Kite, a Gilead company: Current Employment, Current equity holder in publicly-traded company. Walker: Kite, a Gilead company: Current Employment, Current equity holder in publicly-traded company. Kumar: Kite, a Gilead company: Current Employment, Current equity holder in publicly-traded company. Berent-Maoz: Kite, a Gilead company: Current Employment, Current equity holder in publicly-traded company, Honoraria, Patents & Royalties; UCLA: Patents & Royalties. Cinay: Kite, a Gilead company: Current Employment, Current equity holder in publicly-traded company. Vincent: Kite, a Gilead company: Current Employment, Current equity holder in publicly-traded company; Takeda: Current equity holder in publicly-traded company, Patents & Royalties. Langowski: Kite, a Gilead company: Current Employment, Current equity holder in publicly-traded company. Barrett: Kite, a Gilead company: Current Employment, Current equity holder in publicly-traded company.
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