A Study in Nature Communications Reports that NeoImmuneTech’s NT-I7 Enhances CAR-T Cell Expansion, Persistence and Anti-tumor Activity
NT-I7 enhanced the efficacy of CAR-T therapy against acute myeloid leukemia and B cell lymphoma, significantly prolonging survival in murine models.
NT-I7 significantly increased the expansion and persistence of the CAR-T cells, leading to at least a five-fold reduction in the minimum number of CAR-T cells needed at time of infusion to elicit prolonged survival.
NT-I7 enhanced CAR-T cells irrespectively of the targets or tumor types, demonstrating the broad applicability of NT-I7 for cellular therapy.
ROCKVILLE, Md., June 14, 2022 /PRNewswire/ — NeoImmuneTech, Inc. (NIT or “NeoImmuneTech”), a clinical-stage T cell-focused therapeutics company, reported that Nature Communications (Impact Factor: 14.92) published the results of an in vivo study combining the long-acting human IL-7, NT-I7, with chimeric antigen receptor (CAR) T cells directed against CD19+ B cell lymphoma and acute myeloid leukemia.
The study led by Dr. DiPersio and his team at Washington University investigated the impact of NT-I7 on in vivo CAR-T cell expansion and anti-tumor response employing sophisticated models of B cell lymphoma or acute myeloid leukemia and an immune competent syngeneic model of acute promyelocytic leukemia. Utilizing these tools, the group tested whether NT-I7 could expand a less differentiated CAR-T product with improved durability and tumor killing abilities in multiple models of hematological cancer.
Over the past 10 years, CAR-T cell therapy has become routinely used to treat patients with refractory hematologic malignancies. Despite progress, long-lived memory responses and long-term in vivo persistence of CAR-T cells have yet to be consistently achieved to prevent tumor cell escape and clinical relapse.
In the study reported in Nature Communications, NT-I7 protected CD19-targeting CAR-T cells from cell death, enhancing their viability while promoting their expansion in the presence of CD19+ tumor cells. CAR-T cells expanded in the presence of NT-I7 were less differentiated but with equivalent effector cytokine secreting abilities. Treatment of tumor bearing mice with NT-I7 enhanced in vivo expansion and subsequent anti-tumor effects of CAR-T cells targeting CD19+ B cell lymphoma or CD33+ acute-myeloid leukemia. The combination of NT-I7 and CAR-T cells dramatically extended survival. Impressively, co-treatment of tumor bearing mice with NT-I7 reduced the minimum number of CAR-T cells needed to achieve a survival benefit by imparting increased tumor killing abilities to CAR-T cells on a per cell basis and expanding CAR-T cells in vivo. These studies provide compelling evidence that NT-I7 has the potential to enhance CAR-T therapy for the treatment of hematological diseases by promoting CAR-T anti-tumor activity, expansion and persistence.
Dr. Se Hwan Yang, Ph.D., President and Chief Executive Officer of NeoImmuneTech, Inc. said: “This Nature Communications article highlights the exciting properties of NT-I7 that can increase CAR T cells’ functionality and cytotoxicity. Those results demonstrate the broad applicability of NT-I7 for cellular therapy, in addition to its well-documented benefits as a long-acting human IL-7 that has the potential to amplify T cells across the subsets, boost the immune system, and enhance the anti-tumor response in people with hematologic malignancies and solid tumors.”
This study presented in Nature Communications demonstrates the potential for NT-I7 to support impactful clinical use of multiple CAR-T therapies with improved safety and tolerability. Strategic combination of NT-I7 with CD19-targeting CAR-T cells is currently being tested as part of a multi-site clinical trial (NCT05075603) for the treatment of relapsed/refractory large B-cell lymphoma. At ASCO 2022, poster #239b presented the most advanced updates on this study (NIT-112) that aims to show if NT-I7 may increase expansion and persistence of CAR-T, leading to increased tumor response rate and improved clinical outcomes without safety concerns.
Reference: Kim, M.Y., Jayasinghe, R., Devenport, J.M. et al. A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity. Nat Commun 13, 3296 (2022). https://doi.org/10.1038/s41467-022-30860-0
About chimeric antigen receptor (CAR-T) cells therapies
CAR-T cell therapy is a type of treatment in which a patient’s T cells (a type of immune system cell) are changed in the laboratory so they will attack specific cancer cells. T cells are taken from a patient’s blood. Then the gene for a special receptor that binds to a certain protein on the patient’s cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion. Chimeric antigen receptor T-cell therapy is used to treat certain blood cancers, and it is being studied in the treatment of other types of cancer.
About NT-I7 (efineptakin alfa) (rhIL-7-hyFc)
NT-I7 (efineptakin alfa) is the only clinical-stage long-acting human IL-7, and is being developed in oncologic and immunologic indications, where T cell amplification and increased functionality may provide clinical benefit. IL-7 is a fundamental cytokine for naïve and memory T cell development and for sustaining immune response to chronic antigens (as in cancer) or foreign antigens (as in infectious diseases). NT-I7 exhibits favorable PK/PD and safety profiles, making it an ideal combination partner. NT-I7 is being studied in multiple clinical trials in solid tumors and as vaccine adjuvant. Studies are being planned for testing in hematologic malignancies, additional solid tumors and other immunology-focused indications.
About NeoImmuneTech, Inc.
NeoImmuneTech, Inc. (NIT) is a clinical-stage T cell-focused biopharmaceutical company, dedicated to expanding the horizon of immuno-oncology and enhancing immunity to infectious diseases. NIT is led by the scientific founder and inventor of NT-I7 (efineptakin alfa) and has a strong executive team with rich industry experience. NIT is expanding rapidly in personnel and operations, as well as partnering with industry and academic leaders to investigate NT-I7 as monotherapy and in combination with various immunotherapeutics. For more information, please visit www.neoimmunetech.com.
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