A First-in-Human Study of the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-88549968, a T-cell Redirecting Bispecific Antibody for CALR-mutated Myeloproliferative Neoplasms

The purpose of this study is to characterize safety and to determine the Recommended Phase 2 Dose (RP2D[s]) and optimal dosing schedule(s) of JNJ-88549968, in part 1 (Dose Escalation); to characterize the safety of JNJ- 88549968 at RP2D(s), in part 2 (Cohort Expansion).

Start Date20 Dec 2023

Sponsor / Collaborator

Janssen Research & Development LLC

100 Clinical Results associated with CALR x CD3

100 Translational Medicine associated with CALR x CD3

0 Patents (Medical) associated with CALR x CD3

113

Literatures (Medical) associated with CALR x CD3

01 Mar 2025·Biomaterials

Reprogramming tumor microenvironment with precise photothermal therapy by calreticulin nanobody-engineered probiotics

Article

Author: Long, Ying ; Shi, Guangwei ; Jiang, Yuke ; Li, Zhijie ; Zhong, Xiaoru ; Huang, Zhenhui ; Yang, Runwei ; Dong, Zhiyu ; Li, Jiexuan ; Wang, Jigang ; Bai, Chongzhi ; Jia, Lin ; Chen, Chunbo ; Wang, Huifang ; Zheng, Liuhai ; Wei, Jinxi ; Dai, Lingyun

Targeted therapies have revolutionized traditional cancer treatments by precisely targeting tumor cells, enhancing efficacy and safety. Despite this advancement, the proportion of cancer patients eligible for such therapies remains low due to the absence of suitable targets. Here, we investigate whether the translocation of the immunogenic cell death (ICD) marker calreticulin (CALR) from the endoplasmic reticulum (ER) to the cell surface following ICD induction can serve as a target for targeted therapies. To target CALR, a nanobody Nb215 identified from a naïve VHH phage library with high binding affinity to both human and mouse CALR was employed to engineer probiotic EcN 1917. Our results demonstrated that CALR nanobody-modified EcN-215 coupled with the photothermal dye indocyanine green (ICG) was able to exert NIR-II imaging-guide photothermal therapy (PTT). Moreover, PTT with EcN-215/ICG can reshape the tumor microenvironment by enhancing the infiltration of CD45⁺CD3⁺ T cells and CD11b⁺F4/80⁺ macrophages. Furthermore, the antitumor activity of CALR-targeted EcN-215/ICG is synergistically enhanced by blocking CD47-SIRPα axis. Collectively, our study provides a proof of concept for CALR-targeted therapy. Given that CALR translocation can be induced by various anticancer therapies across numerous tumor cell lines, CALR-targeted therapies hold promise as a novel approach for treating multiple types of cancers.

01 Jul 2024·Cytotherapy

Safety and Efficacy of High-Dose Memory CD45RO+ Donor Lymphocyte Infusion in Pediatric Recipients after Hematopoietic Stem Cell Transplantation

Article

Author: Echecopar, Carlos ; Pérez-Martínez, Antonio ; Mozo, Yasmina ; Corral, Dolores ; Yuste, Víctor Jiménez ; Marcos, Antonio ; Aguirre-Portolés, Cristina ; Galán, Victor ; De Paz, Raquel ; Romero, Ana Belén ; Li, Ying ; Sisinni, Luisa ; Triplett, Brandon ; Al-Akioui-Sanz, Karima ; Talleur, Aimee ; Gasior Kabat, Mercedes ; Bueno-Sánchez, David ; Naik, Swati

Memory T selected cells (CD45RA^-/RO⁺) as donor lymphocyte infusion are less capable of producing alloreactivity and graft versus host disease (GvHD) compared with naïve T cells. The objective of this study was to evaluate the safety and efficacy of high-dose memory (CD45RA^-/RO⁺) donor lymphocyte infusion (mDLI) after allogeneic hematopoietic cell transplantation (HCT). Indications for mDLI were "as needed" and "as prophylactic regimen." Sixty-one children diagnosed with malignant (82%) and non-malignant diseases (18%) received 241 mDLIs. Patients received a median of three infusions (range 1‒13) of mDLI with a median infused dose of 1.35 × 10⁷/kg CD45RO⁺ containing 8.96 × 10⁶/kg CD3⁺CD45RO⁺ and 3.81 × 10³/kg CD3⁺CD45RA⁺. De novo GvHD developed in 7 patients following 4% of the mDLI infusions. Among patients with GvHD before mDLI, this condition worsened following 6 infusions (11%) in the 3 patients with grade II-IV acute GvHD. A decrease in cytomegalovirus viral load followed 65% of mDLI infusions. Two-year overall survival (OS) for the total cohort was 64% (95% CI 57%‒72%). For patients receiving prophylactic mDLI, the two-year non-relapse mortality was 10% (95% CI 9%‒11%). In summary, high-dose mDLI is feasible and safe, with a relatively low risk of severe GvHD even in patients with active GvHD. Importantly, mDLI was associated with positive effects, including enhanced control of CMV viremia.

01 Apr 2024·Oral Diseases

Carbon quantum dots as immune modulatory therapy in a Sjögren's syndrome mouse model

Article

Author: Ge, Xuejun ; Ding, Chong ; Fu, Cuicui ; Jiang, Nan ; Bikker, Floris J ; Qin, Xiaoyun ; Zhang, Jin ; Zhang, Ting ; Song, Yeqing ; Shao, Wenlong ; Wu, Gang ; Yang, Jiaqi

AbstractObjectivesThe objective of the study was to evaluate the therapeutic effects of carbon quantum dots (CQDs) in immunomodulation on non‐obese diabetic (NOD) mice, as the model for Sjögren's syndrome (SS).MethodsCarbon quantum dots were generated from Setaria viridis via a hydrothermal process. Their toxic effects were tested by cell viability and blood chemistry analysis, meanwhile therapeutic effects were investigated in NOD mice in the aspects of saliva flow, histology, and immune cell distribution.ResultsCarbon quantum dots, with rich surface chemistry and unique optical properties, showed non‐cytotoxicity in vitro or no damage in vivo. Intravenously applied CQDs alleviated inflammation in the submandibular glands in NOD mice after 6‐week treatments. The inflammatory area index and focus score were significantly decreased in CQD‐treated mice. Besides, the levels of anti‐SSA and anti‐SSB were decreased in the presence of CQDs. The stimulated saliva flow rates and weight of submandibular glands were significantly increased in CQD‐treated mice by reducing the apoptosis of cells. The CD3+ and CD4+ T cells distributed around the ducts of submandibular glands were significantly decreased, while the percentage of Foxp3+ cells was higher in CQD‐treated mice than that in the control group.ConclusionsOur findings suggest that CQDs may ameliorate the dysregulated immune processes in NOD mice.

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