The main objective of this clinical study is to evaluate the safety and tolerability of NK-92/5.28.z and to determine the maximum tolerated dose or maximum feasible dose (MFD). Recommended phase 2 doses both for intraoperative injections only (RP2Diio) and repetitive injections (RP2Dri) will be determined. Frequent side effects and target organs of toxicity and their severity, duration and reversibility will be determined. Furthermore, pharmacokinetics and pharmacodynamics will be examined. In addition, potential signs of anti-tumor activity of NK-92/5.28.z cells will be analyzed. In the separate "CAR2BRAIN-Check" cohort, combination therapy of NK-92/5.28.z with the anti-PD-1 antibody Ezabenlimab (BI 754091) will be tested.

Start Date01 Dec 2017

Sponsor / Collaborator

Hospital of the Johann Wolfgang Goethe University

[+3]

100 Clinical Results associated with HER2.taNK(NantKwest)

100 Translational Medicine associated with HER2.taNK(NantKwest)

100 Patents (Medical) associated with HER2.taNK(NantKwest)

Literatures (Medical) associated with HER2.taNK(NantKwest)

01 Jun 2024·Molecular Therapy: Oncology

Bortezomib promotes the TRAIL-mediated killing of resistant rhabdomyosarcoma by ErbB2/Her2-targeted CAR-NK-92 cells via DR5 upregulation

Article

Author: Hartig, Leonie ; Salzmann-Manrique, Emilia ; Merker, Michael ; Wels, Winfried S ; Weinelt, Nadine ; Heim, Catrin ; Moser, Laura M ; van Wijk, Sjoerd J L ; Rettinger, Eva ; Klusmann, Jan-Henning ; Tonn, Torsten ; Bader, Peter

Treatment resistance and immune escape are hallmarks of metastatic rhabdomyosarcoma (RMS), underscoring the urgent medical need for therapeutic agents against this disease entity as a key challenge in pediatric oncology. Chimeric antigen receptor (CAR)-based immunotherapies, such as the ErbB2 (Her2)-CAR-engineered natural killer (NK) cell line NK-92/5.28.z, provide antitumor cytotoxicity primarily through CAR-mediated cytotoxic granule release and thereafter-even in cases with low surface antigen expression or tumor escape-by triggering intrinsic NK cell-mediated apoptosis induction via additional ligand/receptors. In this study, we showed that bortezomib increased susceptibility toward apoptosis in clinically relevant RMS cell lines RH30 and RH41, and patient-derived RMS tumor organoid RMS335, by upregulation of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor DR5 in these metastatic, relapsed/refractory (r/r) RMS tumors. Subsequent administration of NK-92/5.28.z cells significantly enhanced antitumor activity in vitro. Applying recombinant TRAIL instead of NK-92/5.28.z cells confirmed that the synergistic antitumor effects of the combination treatment were mediated via TRAIL. Western blot analyses indicated that the combination treatment with bortezomib and NK-92/5.28.z cells increased apoptosis by interacting with the nuclear factor κB, JNK, and caspase pathways. Overall, bortezomib pretreatment can sensitize r/r RMS tumors to CAR- and, by upregulating DR5, TRAIL-mediated cytotoxicity of NK-92/5.28.z cells.

01 Dec 2023·Archivum Immunologiae et Therapiae Experimentalis

In Situ Programming of CAR-T Cells: A Pressing Need in Modern Immunotherapy

Review

Author: Śledź, Marta ; Wojciechowska, Alicja ; Zagożdżon, Radosław ; Kaleta, Beata

AbstractChimeric antigen receptor-T (CAR-T) cell-based therapy has become a successful option for treatment of numerous hematological malignancies, but also raises hope in a range of non-malignant diseases. However, in a traditional approach, generation of CAR-T cells is associated with the separation of patient’s lymphocytes, their in vitro modification, and expansion and infusion back into patient’s bloodstream. This classical protocol is complex, time-consuming, and expensive. Those problems could be solved by successful protocols to produce CAR-T cells, but also CAR-natural killer cells or CAR macrophages, in situ, using viral platforms or non-viral delivery systems. Moreover, it was demonstrated that in situ CAR-T induction may be associated with reduced risk of the most common toxicities associated with CAR-T therapy, such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and “on-target, off-tumor” toxicity. This review aims to summarize the current state-of-the-art and future perspectives for the in situ-produced CAR-T cells. Indeed, preclinical work in this area, including animal studies, raises hope for prospective translational development and validation in practical medicine of strategies for in situ generation of CAR-bearing immune effector cells.

20 Nov 2023·Chinese Medical Journal

Targeting the HIV reservoir: chimeric antigen receptor therapy for HIV cure

Review

Author: Wang, Hu ; Guo, Na ; Su, Bin ; Zhang, Tong ; Lambotte, Olivier ; Li, Shuang

AbstractAlthough antiretroviral therapy (ART) can reduce the viral load in the plasma to undetectable levels in human immunodeficiency virus (HIV)-infected individuals, ART alone cannot completely eliminate HIV due to its integration into the host cell genome to form viral reservoirs. To achieve a functional cure for HIV infection, numerous preclinical and clinical studies are underway to develop innovative immunotherapies to eliminate HIV reservoirs in the absence of ART. Early studies have tested adoptive T-cell therapies in HIV-infected individuals, but their effectiveness was limited. In recent years, with the technological progress and great success of chimeric antigen receptor (CAR) therapy in the treatment of hematological malignancies, CAR therapy has gradually shown its advantages in the field of HIV infection. Many studies have identified a variety of HIV-specific CAR structures and types of cytolytic effector cells. Therefore, CAR therapy may be beneficial for enhancing HIV immunity, achieving HIV control, and eliminating HIV reservoirs, gradually becoming a promising strategy for achieving a functional HIV cure. In this review, we provide an overview of the design of anti-HIV CAR proteins, the cell types of anti-HIV CAR (including CAR T cells, CAR natural killer cells, and CAR-encoding hematopoietic stem/progenitor cells), the clinical application of CAR therapy in HIV infection, and the prospects and challenges in anti-HIV CAR therapy for maintaining viral suppression and eliminating HIV reservoirs.

100 Deals associated with HER2.taNK(NantKwest)

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Indication	Highest Phase	Country/Location	Organization	Date
Glioblastoma	Phase 1	DE	NantKwest, Inc.	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EHA2015	Not Applicable	Neoplasms	17	NKIL15	(kkczlxxwbn) = vaybvyqhwv wwcqtutilk (gmjygzcwxw ) View more	-	21 May 2015
				CLINICAL GRADE ACTIVATED NATURAL KILLER PRODUCTS (NKAE)	(xphsfzyknb) = ehzptqrutz lxpyjtxeit (rgwabdmmia, 28 - 1547) View more

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