On April 23, 2022 Nektar Therapeutics (Nasdaq: NKTR) announced that collaborators from the Cairo Laboratory at New York Medical College reported data from several preclinical studies demonstrating the potential of NKTR-255 to enhance the anti-tumor activities of different CAR-T therapies in a variety of cancer preclinical models (Press release, Nektar Therapeutics, APR 23, 2022, View Source;transplantation–cellular-therapy-meetings-of-astct-and-cibmtr-301531360.html [SID1234612877]). Presentations include an oral presentation by Wen Luo, Ph.D., assistant professor of pediatrics at NYMC, on in vivo and in vitro efficacy of NKTR-255 combined with anti-MCAMa CARb modified Natural Killer (NK) cells in several tumor models, and a poster presentation by Yaya Chu, Ph.D., assistant professor of pediatrics at NYMC, presenting studies of NKTR-255 in combination with ex vivo expanded anti-CD19 CAR NK cells and anti-CD20 or anti-CD79 antibodies in models of Burkitt Lymphoma (BL).

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"Our research builds on the body of knowledge for the role of an agent which activates the full IL-15 biology pathway in the field of cell therapy," said Mitchell S. Cairo, M.D., director of the Cairo Laboratory, chief of pediatric hematology, oncology and stem cell transplantation, director of the Children and Adolescent Cancer and Blood Diseases Center, associate chairman of the Department of Pediatrics and professor of pediatrics, medicine, pathology, microbiology and immunology and cell biology and anatomy at NYMC. "My lab’s findings show that NKTR-255’s ability to expand and proliferate NK cells resulted in the enhancement of the efficacy of two different CAR therapies in our preclinical models."

The oral presentation will be virtually live streamed on Saturday April 23rd, 2022 at 3:00 PM MT and is accessible through the meeting organizer’s website at View Source These presentations are available for download at View Source

Key details and takeaways from the two collaborator presentations include:

Abstract 27: "Targeting Ewing sarcoma, Osteosarcoma and Neuroblastoma with Anti-MCAM Chimeric Antigen Receptor Modified Natural Killer Cells" Luo, W., et al.
Presentation Type: Oral Presentation
Presenting Author: Wen Luo, Ph.D.
Session: Oral Abstract – Session C – Immune and Gene Therapy
Virtual Live Stream of the presentation will begin at 3:00 PM MT on Saturday April 23rd, 2022

NKTR-255 enhances expression of NK cell-activating receptors, stimulates NK cell proliferation and sustains NK cell expansion
NKTR-255 enhances anti-MCAM CAR NK cell cytotoxicity against Ewing sarcoma, osteosarcoma and neuroblastoma in vitro
Anti-MCAM CAR NK alone or in combination with NKTR-255 significantly decrease lung metastasis and prolong animal survival in an Ewing sarcoma orthotopic mouse model
Abstract 201: "Optimizing Chimeric Antigen Receptor (CAR) Engineered NK Cell- Mediated Cytotoxicity Combined with anti-CD20 or anti-CD79 Therapeutic Antibodies and NKTR-255 in Burkitt Lymphoma (BL)" Chu, Y., et al.
Presentation Type: Poster

NKTR-255 + obinutuzumab, a humanized type II anti-CD20 monoclonal antibody (mAb) glycoengineered to enhance Fc receptor affinity, significantly enhanced the in vitro cytotoxicity of anti-CD19 CAR NK compared to controls against multiple Burkitt lymphoma model (Raji) (p<0.0081) as well as release of perforin (p<0.05), IFN-g (p<0.001) and granzyme B (p<0.01)
These results were further confirmed utilizing Raji-2R and Raji-4RH cells
NKTR-255 + polatuzumab vedotin (PV), an anti-CD79 mAb glycoengineered to enhance Fc receptor affinity, significantly enhanced the in vitro cytotoxicity of anti-CD19 CAR NK cells compared to control groups such as expanded NK cells +NKTR-255 + PV against Raji (p<0.0001), Raji-2R (p<0.0003), and Raji-4RH (p<0.0311), as well as enhanced release of Interferon gamma (IFN-γ) and perforin
Posters will be on display Sunday, April 24, 2022 from 11:00 am to 7:15 pm; Monday, April 25, 2022 from 7:00 am to 7:00 pm; Tuesday, April 26, 2022 from 7:00 am to 12:00pm (all times MDT)

Poster Receptions are on Sunday, April 24, 2022 from 6:30 pm to 7:15 pm MDT

About NYMC
Founded in 1860, New York Medical College is one of the oldest and largest health sciences colleges in the country with nearly 1,500 students and 330 residents and clinical fellows, more than 2,600 faculty members and 23,200 living alumni. The College, which joined Touro University in 2011, is located in Westchester County, New York, and offers degrees from the School of Medicine, the Graduate School of Basic Medical Sciences, the School of Health Sciences and Practice, the Touro College of Dental Medicine at NYMC, and the Touro College School of Health Sciences’ nursing program at NYMC. NYMC provides a wide variety of clinical training opportunities for students, residents, and practitioners. For more information, visit www.nymc.edu.

About NKTR-255
NKTR-255 is an investigational IL‐15 receptor agonist designed to boost the immune system’s natural ability to fight cancer. NKTR-255 increases the proliferation and survival of cancer-killing natural killer (NK) cells and memory CD8+ T cells. NKTR-255 engages the entire IL-15 receptor complex (IL‐15Rα/IL‐15Rβγ) to enhance the formation of long-term immunological memory, which may lead to sustained antitumor immune response.

NKTR-255 is specifically engineered using Nektar’s expertise in polymer chemistry to mimic the natural biological activity of the body’s own IL-15, resulting in optimal activation of the IL-15 pathway. NKTR-255 is uniquely designed to overcome the challenges of recombinant IL-15, which has to be given in high doses due to rapid clearance from the body, limiting its utility due to toxicity and lack of convenience and use.