NKTR-214 is a CD122-biased agonist designed to grow specific cancer-killing T cells and natural killer (NK) cell populations in the body which fight cancer, which are known as endogenous tumor-infiltrating lymphocytes (TILs). NKTR-214 stimulates these cancer-killing immune cells in the body by targeting CD122 specific receptors found on the surface of these cancer-killing immune cells, known as CD8+ effector T cells and Natural Killer (NK) cells. NKTR-214 is currently in Phase 1/2 clinical development.
NKTR-255 is a memory T cell stimulating cytokine designed to engage the IL-15 pathway to induce long-term T cell activation and improve the quality of T cell memory response to treat cancer. Through optimal engagement of the IL-15Rα/IL-2Rγ receptor complex, NKTR-255 stimulates proliferation and survival of CD8+ T cells, natural killer (NK) cells and enhances formation of long-term immunological memory which may lead to sustained anti-tumor immune response.
Details of the five preclinical presentations made at AACR are as follows:
Presenter:
Abstract 1598/Poster 6: "Single agent NKTR-214, an engineered IL2 pathway agonist, localizes in tumor tissue, increases immune infiltrates and prolongs survival in rodent (rattus) glioblastoma (GBM)"
Session: Cytokines: The First Modern Immunotherapies
- NKTR-214 single agent provides durable responses as a single agent in an aggressive orthotopic rat brain tumor model.
- Treatment of even very large tumors is effective with NKTR-214, prolonging survival in a significant proportion of animals; CD8+ T cells infiltrate into the brain tumors after NKTR-214 therapy.
- The marked increase in survival in this aggressive rodent brain tumor model after treatment with single agent NKTR-214 suggests its potential benefit for the treatment of human malignant glioma.
Presenter:
Abstract 1604/Poster 12: "NKTR-214 Synergizes with Radiotherapy to Drive Tumor Regression"
Session: Cytokines: The First Modern Immunotherapies
- NKTR-214 combines positively with radiation therapy which is a standard of care for multiple tumor types and is a readily available therapy.
- Gene expression patterns reveal a strong T cell activation signature including up-regulation of tumor-killing granzymes and perforins.
- Combined therapy increased the frequency of tumor-reactive CD8 T cells in the target (irradiated) tumors as measured by increased TCR ligation (Nur77-GFP+) and AH1-A5 tetramer staining.
Presenter:
Abstract 2671/Poster 30: "Antitumor activity of NKTR-214 in combination with Adopted Cell Transfer (ACT) in an aggressive murine melanoma"
Session: Immune Response to Hematopoietic Tumors:
- NKTR-214 improves the antitumor activity of adoptive cellular therapy in an aggressive murine melanoma model.
- Treatment with NKTR-214 + ACT robustly mobilizes T cells into the tumor where they durably persist.
- The robust and long-lasting effect of NKTR-214 supports its potential use in combination with cell-based therapeutics.
Presenter:
Abstract 1617/Poster 25: "Mechanistic modeling of the pharmacokinetics, pharmacodynamics and receptor pharmacology of NKTR-214: A kinetically-controlled CD122 agonist for cancer immunotherapy"
Session: Cytokines: The First Modern Immunotherapies
- NKTR-214 significantly favors occupancy at IL-2 receptor βγ compared to the IL-2 receptor αβγ.
- NKTR-214 delivers a controlled, sustained, and biased signal through the IL-2 receptor complex.
Presenter:
Abstract 1603/Poster 11: "NKTR-255 engages the IL-15 pathway driving CD8 T cell survival and CD8 memory T cell proliferation"
Session: Cytokines: The First Modern Immunotherapies
- NKTR-255 induces multiple memory CD8+ T cell subtypes, including effector, central and stem memory populations.
- Single dose NKTR-255 results in sustained IL-15-mediated activity not achievable with conventional IL-15.
- NKTR-255 has single agent efficacy in the CT-26 lung metastatic model, demonstrating significant lung nodule inhibition.
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