Nektar Therapeutics (Nasdaq: NKTR) today announced the publication of preclinical data in Blood Advances, the open-access journal of the American Society of Hematology, highlighting the effects of NKTR-255, a novel polymer-conjugated human IL-15, on the efficacy of human CD19 CAR-T cells in a xenogeneic lymphoma model and on CD8+ T effector cell (Tcell) and natural killer (NK) cell proliferation in non-human primates.
“The findings published today reinforce the foundational rationale behind the clinical development program we’re pursuing of NKTR-255 enhancing CAR-T cell therapies,” said Jonathan Zalevsky, Ph.D., Chief Research & Development Officer at Nektar. “We are looking forward to progressing our research in combination with cell therapies and are excited to launch our Phase 2/3 clinical trial of NKTR-255 following approved CAR-T cell therapies in patients with relapsed or refractory diffuse large B-cell Lymphoma.”
The data from this publication demonstrate that NKTR-255 not only enhanced in vivo proliferation and accumulation of T and NK cells in non-human primates, but also demonstrated enhanced in vivo antitumor efficacy of human CD19 CAR-T in lymphoma-bearing immunodeficient mice.
“In contrast to mice treated with CAR-T alone, those that received CAR-T and NKTR-255 had markedly higher CAR-T counts in blood and marrow that were sustained after tumor clearance, without evidence of persistent proliferation or ongoing activation/exhaustion assessed by Ki-67 and inhibitory receptor co-expression,” said Dr. Cameron Turtle, senior author on the publication and CLEARbridge Chair of Cancer Immunotherapy at Sydney Medical School. “These data support the ongoing clinical research of combined CAR-T and NKTR-255 for B-cell malignancies.”
Key findings are summarized below:
- Serum IL-15 concentration is independently associated with longer CD19 CAR-T persistence in humans
- NKTR-255 promotes CD8+ effector and memory T and NK cell accumulation in non-human primates
- NKTR-255 enhances proliferation and survival of human CD19 CAR-T at low target cell abundance
- NKTR-255 enhances accumulation and efficacy of human CD19 CAR-T in lymphoma bearing immunodeficient mice
The full citation of this article can be accessed here.
NKTR-255 is a biologic that targets the IL-15 pathway in order to activate the body’s innate and adaptive immunity. Through optimal engagement of the IL-15 receptor complex, NKTR-255 is designed to enhance functional NK cell populations and formation of long-term immunological memory, which may lead to sustained and durable anti-tumor immune response.
Preclinical findings suggest NKTR-255 has the potential to synergistically combine with antibody-dependent cellular cytotoxicity molecules as well as to enhance CAR-T therapies.
There are two ongoing investigator sponsor trials evaluating NKTR-255 following treatment with a CAR-T cell therapy. Fred Hutchinson Cancer Center is conducting a Phase 1 study evaluating NKTR-255 in combination with CD19 CAR-T cell therapy in patients with relapsed or refractory large B-cell lymphoma (NCT05359211), and Stanford University is conducting a Phase 1 study evaluating NKTR-255 in combination with CD19/22 CAR-T cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (NCT03233854).
Nektar is also currently designing a Nektar-sponsored Phase 2/3 study combining NKTR-255 with approved CAR-T cell therapies in diffuse large B-cell lymphoma, which it aims to initiate in the first quarter of 2023.