Nesfrotamig  (Synonyms: YH32367; ABL105)

Nesfrotamig (YH32367; ABL105) is a bispecific activator targeting HER2 and 4-1BB. The K_d values of Nesfrotamig for human HER2 and human 4-1BB are 0.48 nM and 3.36 nM, respectively. By blocking tumor cell growth signals, activating HER2-dependent local 4-1BB in tumors to maintain T cell survival, and inducing NK cell-mediated antibody-dependent cellular cytotoxicity, Nesfrotamig enhances the cytotoxicity and tumor infiltration ability of immune cells. Nesfrotamig promotes the generation of tumor-specific memory T cells, drives T cell-mediated tumor lysis, exhibits significant anti-tumor efficacy against both HER2-positive and HER2-low-expressing tumors, and shows synergistic activity when combined with anti-PD-1 antibodies. In cynomolgus monkey studies, Nesfrotamig demonstrates good safety and is suitable for research related to HER2-positive and HER2-low-expressing tumors^[1][2][3].

IgG1-kappa-[scFv]2-lambda-heavy

Human IgG1 kappa, Isotype Control

Human

ERBB2 & TNFRSF9

Nesfrotamig binds to 4-1BB-expressing Jurkat cells and HER2-expressing HCC1954 cells in a dose-dependent manner^[1].
Nesfrotamig induces 4-1BB activation in a HER2 expression-dependent manner across multiple human cancer cell lines, with higher induction fold observed in cell lines with higher normalized HER2 expression levels^[1].
Nesfrotamig (0.01 μg/mL-10 μg/mL) inhibits the proliferation of BT-474 cells in a dose-dependent manner, and its potency is comparable to that of Trastuzumab (HY-P9907)^[1].
ABL105 potently activates the 4-1BB signaling pathway in three HER2-expressing tumor cell lines, NCI-N87, JIMT-1 and HCC1954^[2].
ABL105 induces IFN-γ secretion and subsequent tumor cell lysis in a co-culture system of hPBMC and HER2-expressing tumor cells^[2].
YH32367 induces IFN-γ secretion and subsequent tumor cell death in a co-culture system of hPBMC and HER2-expressing tumor cells^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Nesfrotamig (ABL105) (10 mg/kg; i.v.; twice weekly; 4 weeks) delivers potent tumor growth inhibition (~90% reduction in mean tumor volume vs control) and enhances tumor-specific immune cell infiltration while limiting systemic immune activation in humanized HCC1954 breast cancer-bearing mice^[1].
Nesfrotamig (ABL105) (10 mg/kg; i.p.; twice weekly; 4 weeks) induces complete tumor regression in h4-1BB KI mice bearing hHER2/MC38 colorectal tumors and establishes durable, tumor-specific memory T cell immunity that prevents tumor re-challenge^[1].
Nesfrotamig exhibits superior tumor-eradicating efficacy and induces long-term anti-tumor immunity in MC38/hHER2-bearing h4-1BB KI mice compared to benchmark HER2-targeted and 4-1BB/HER2-bispecific agents^[3].
Nesfrotamig demonstrates greater monotherapy efficacy than a benchmark 4-1BB/HER2-bispecific agent in HER2-low tumor-bearing h4-1BB KI mice, and exhibits synergistic anti-tumor activity when combined with anti-PD-1 antibody^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

2064  [NCBI] & 3604  [NCBI]

P04626 & Q07011

ELISA, FACS, Functional assay

Unconjugated

The product can be reconstituted/diluted with sterile PBS or saline.

2966936-23-0

Liquid

Colorless to light yellow

N/A

Shipping with dry ice.

Please refer to the lot-specific COA for specific buffer information.

Please store the product under the recommended conditions in the Certificate of Analysis.

• 
  IgG1-kappa-[scFv]2-lambda-heavy

• [1]. Song M Y, et al. A novel HER2/4-1BB bispecific antibody, YH32367 (ABL105) shows potent anti-tumor effect through tumor-directed T cell activation[J]. Cancer Res, 2020, 80(16_Supplement): 6524-6524.

  [2]. Lee E, et al. 544P a novel HER2/4-1BB bispecific antibody, YH32367 (ABL105) exerts significant anti-tumor effects through tumor-directed T cell activation[J]. Annals of Oncology, 2021, 32: S607-S608.

  [3]. Lee E, et al. The HER2/4-1BB bispecific antibody, YH32367 (ABL105) demonstrates optimal efficacy and safety for HER2-expressing tumors and exhibits synergistic efficacy when combined with anti-PD-L1[J]. Cancer Research, 2024, 84(6_Supplement): 6354-6354.