GEMoaB Announces Publication of Pre-Clinical Proof-of-Concept Data on UniCAR-modified Off-the-shelf Natural Killer Cells in 'Nature Scientific Reports'
- Category: DNA RNA and Cells
- Published on Wednesday, 18 March 2020 09:38
- Hits: 764
DRESDEN, Germany I March 17, 2020 I GEMoaB, a biopharmaceutical company focused on the development of next-generation immunotherapies for hard-to-treat cancers, today announced that "Nature Scientific Reports" has published pre-clinical proof-of-concept data on UniCAR-modified off-the-shelf Natural Killer (NK) cells targeting GD2-expressing tumors (Mitwasi et al. 2020, 10:2141). The data generated by researchers of the Helmholtz-Center Dresden-Rossendorf (HZDR) provide further evidence on the unique flexibility of GEMoaB´s proprietary UniCAR platform.
CAR-T cell therapy holds great promise for treating a wide range of malignancies. Nevertheless, the CAR-T approach faces multiple challenges, including the risk of acute and long-term toxicities, a current lack of suitable targets, insufficient engraftment and persistence especially in solid tumors. In addition, currently commercially available CAR-T products can only be derived from individual patients, adding significant complexity and cost to the autologous manufacturing process.
GEMoaB's rapidly switchable universal CAR platform UniCAR promises an improved therapeutic window and increased efficacy and safety over conventional CAR-T therapies in hematological malignancies and solid tumors. As soluble adaptors termed targeting modules (TMs) are used to provide the antigen-specificity to activate UniCAR gene-modified T-cells (UniCAR-T), the manufacturing process is significantly simplified by the ability to use the same UniCAR-T effector cell against multiple antigens and tumor types.
Natural killer (NK) cells genetically engineered to express a CAR (CAR-NK) have recently emerged as promising candidates for effective cancer treatment. Off-the-shelf CAR-NK cells from an allogeneic source, such as cord blood, can be safely administered without the need for full HLA matching, therefore eliminating the need to produce a unique CAR product for each patient. Furthermore, allogeneic CAR-NK cells have a proven track record of safety due to their lack of causing cytokine release syndrome (CRS).
In a recent publication in Nature Scientific Reports (Mitwasi et al. 2020, 10:2141), researchers of the HZDR combined the advantages of the UniCAR approach with the off-the shelf capabilities of NK cells. The publication provides proof-of-concept for a universal off-the-shelf cellular therapeutic based on UniCAR-modified NK-92 cells retargeted to GD2-expressing tumors by GD2-specific TMs. Redirected UniCAR-NK-92 cells induced specific and effective killing of GD2-expressing cells in vitro and in vivo, associated with enhanced interferon-γ production.
"We are very pleased that our co-founder Prof. Michael Bachmann and researchers of the HZDR could demonstrate that GEMoaB's highly flexible UniCAR system can be readily applied to continuously expanding off-the-shelf NK cells, which in combination with GD2-specific TMs efficiently target and lyse GD2-expressing tumor cells such as neuroblastoma and melanoma," said Prof. Gerhard Ehninger, co-founder and CMO of GEMoaB. "UniCAR-NK cells could represent an additional universal and modular off-the-shelf platform that would allow the use of TMs against multiple antigen targets for an effective and safe therapy of cancer."
"As we are progressing with our clinical development plans for UniCAR-T-CD123 in hematological malignancies and UniCAR-T-PSMA in solid tumors, we are developing a deep pipeline of TMs directed against a wide variety of blood and solid tumor cancers," said Dr. Armin Ehninger, Chief Scientific Officer of GEMoaB. "We believe that UniCAR-NK cells could further enhance the unique flexibility of our platform by combining the advantages of UniCAR with the safety and off-the-shelf capabilities of NK cells."
GEMoaB is a privately-owned, clinical-stage biopharmaceutical company that is aiming to become a globally leading biopharmaceutical company. By advancing its proprietary UniCAR, RevCAR and ATAC platforms, the company will discover, develop, manufacture and commercialize next generation immunotherapies for the treatment of cancer patients with a high unmet medical need.
GEMoaB has a broad pipeline of product candidates in pre-clinical and clinical development for the treatment of hematological malignancies as well as solid tumors. Its clinical stage assets GEM333, an Affinity-Tailored Adaptor for T-Cells (ATAC) with binding specificity to CD33 in relapsed/refractory AML, and GEM3PSCA, an ATAC with binding specificity to PSCA for the treatment of castrate-resistant metastatic prostate cancer and other PSCA expressing late-stage solid tumors, are currently investigated in Phase I studies and globally partnered with Bristol-Myers Squibb/Celgene. A Phase IA dose-finding study of the first UniCAR asset, UniCAR-T-CD123 for treatment of relapsed/refractory AML and ALL has been initiated, UniCAR-T-PSMA against CRPC and other PSMA-expressing late-stage solid tumors, is planned to be tested in a Phase I study initiated by H2 2020.
Manufacturing expertise, capability and capacity are key for developing cellular immunotherapies for cancer patients. GEMoaB has established a preferred partnership with its sister company Cellex in Cologne, a world leader in manufacturing hematopoietic blood stem cell products and a leading European CMO for CAR-T cells, co-operating in that area with several large biotech companies.
GEMoaB is developing a rapidly switchable universal CAR-T platform, UniCAR, to improve the therapeutic window and increase efficacy and safety of CAR-T cell therapies in more challenging cancers, including solid tumors. Standard CAR-T cells depend on the presence and direct binding of cancer antigens for activation and proliferation. An inherent key feature of the UniCAR platform is a rapidly switchable on/off mechanism (less than 4 hours after interruption of TM supply) enabled by the short pharmacokinetic half-life and fast internalization of soluble adaptors termed targeting modules (TMs). These TMs provide the antigen-specificity to activate UniCAR gene-modified T-cells (UniCAR-T) and consist of a highly flexible antigen-binding moiety, linked to a small peptide motif recognized by UniCAR-T.
GEMoaB's platform of Affinity-Tailored Adaptors for T-Cells (ATAC) is characterized by high binding affinity to tumor antigens and lower affinity to the CD3 antigen on effector T-cells, preventing T-cell auto-activation in pre-clinical models. Safety and tolerability of the treatment are also increased by the relatively short serum half-life (60 min). The use of fully humanized antibodies reduces the risk of immunogenicity even in case of chronic dosing. Half-life extended ATACs are in pre-clinical development.
More information can be found at www.gemoab.com.