CD47 inhibitors(Cluster of differentiation 47 inhibitors), ICAM-1 inhibitors(Intercellular adhesion molecule-1 inhibitors), ADCC(Antibody-dependent cell-mediated cytotoxicity (ADCC) effects)

Therapeutic Areas

NeoplasmsHemic and Lymphatic Diseases

Active Indication

Hematologic NeoplasmsSolid tumor

Inactive Indication-

Originator Organization

Virtuoso Therapeutics, Inc.

Active Organization

Virtuoso Therapeutics, Inc.

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

100 Clinical Results associated with Anti-CD47/ICAM-1 bispecific antibody (Virtuoso Therapeutics)

100 Translational Medicine associated with Anti-CD47/ICAM-1 bispecific antibody (Virtuoso Therapeutics)

100 Patents (Medical) associated with Anti-CD47/ICAM-1 bispecific antibody (Virtuoso Therapeutics)

Literatures (Medical) associated with Anti-CD47/ICAM-1 bispecific antibody (Virtuoso Therapeutics)

01 May 2024·Drug Resistance Updates

Development and evaluation of a human CD47/HER2 bispecific antibody for Trastuzumab-resistant breast cancer immunotherapy

Article

Author: Ji, Zhenyu ; Gao, Le ; Li, Song ; Xu, Linping ; Fan, Dandan ; Wang, Fang ; Song, Yongping ; Tian, Wenzhi ; Bian, Zhilei ; Jin, Shuiling ; Liu, Mengmeng ; Shi, Jianxiang ; Zheng, Yichao ; Shi, Xiaojing ; Li, Wei ; Xu, Xiaolu ; Zhang, Binglei ; Zhou, Jian ; Gao, Mengya

The treatment for trastuzumab-resistant breast cancer (BC) remains a challenge in clinical settings. It was known that CD47 is preferentially upregulated in HER2⁺ BC cells, which is correlated with drug resistance to trastuzumab. Here, we developed a novel anti-CD47/HER2 bispecific antibody (BsAb) against trastuzumab-resistant BC, named IMM2902. IMM2902 demonstrated high binding affinity, blocking activity, antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and internalization degradation effects against both trastuzumab-sensitive and trastuzumab-resistant BC cells in vitro. The in vivo experimental data indicated that IMM2902 was more effective than their respective controls in inhibiting tumor growth in a trastuzumab-sensitive BT474 mouse model, a trastuzumab-resistant HCC1954 mouse model, two trastuzumab-resistant patient-derived xenograft (PDX) mouse models and a cord blood (CB)-humanized HCC1954 mouse model. Through spatial transcriptome assays, multiplex immunofluorescence (mIFC) and in vitro assays, our findings provided evidence that IMM2902 effectively stimulates macrophages to generate C-X-C motif chemokine ligand (CXCL) 9 and CXCL10, thereby facilitating the recruitment of T cells and NK cells to the tumor site. Moreover, IMM2902 demonstrated a high safety profile regarding anemia and non-specific cytokines release. Collectively, our results highlighted a novel therapeutic approach for the treatment of HER2⁺ BCs and this approach exhibits significant anti-tumor efficacy without causing off-target toxicity in trastuzumab-resistant BC cells.

01 Dec 2022·Journal of Translational MedicineQ2 · MEDICINE

SIRPα and PD1 expression on tumor-associated macrophage predict prognosis of intrahepatic cholangiocarcinoma

Q2 · MEDICINE

ArticleOA

Author: Xu, Linping ; Yang, Hui ; Yan, Meimei ; Li, Wei

AbstractBackgroundThe phagocytosis checkpoints of CD47/SIRPα, PD1/PDL1, CD24/SIGLEC10, and MHC/LILRB1 have shown inhibited phagocytosis of macrophages in distinct tumors. However, phagocytosis checkpoints and their therapeutic significance remain largely unknown in intrahepatic cholangiocarcinoma (ICC) patients.MethodsWe analyzed sequencing data from the Cancer Genome Atlas (TCGA) and identified differently expressed genes between tumors and para‐tumors. Then, we investigated the expression of CD68, SIRPα, PD1, and SIGLEC10 by IHC in 81 ICC patients, and the clinical significance of these markers with different risk factors was also measured.ResultsTumor infiltration immune cells analysis from the TCGA data revealed that macrophages significantly increased. Further analysis showed that M0 macrophages were significantly higher and M2 macrophages were significantly lower in ICC compared with paracancerous tissues, while there was no significant difference in M1 macrophages. We then examined some of M1 and M2 markers, and we found that M1 markers (iNOS, TNF, IL12A, and B) increased, while M2 markers (ARG1 and CD206) decreased in ICCs compared with paracancerous tissues. Furthermore, the expression of CD68, SIRPα, PD1, and SIGLEC10 increased significantly, but LILRB1 expression did not. We also examined the expression of CD68, SIRPα, PD1, and SIGLEC10 in 81 ICC patients by IHC, which revealed a similar expression pattern to that which emerged from the TCGA data. Upon analyzing the correlation between these markers and the progression of ICC patients, we found that the high expression of CD68, SIRPα, and PD1 are correlated with poor progression among ICC patients, while SIGLEC10 shows no correlation. More SIRPα+ or PD1+ TAMs were observed in the tumor tissues of ICC patients with HBV infections compared to non‐HBV‐infected patients. Multivariate analysis indicated that SIRPα and PD1 expression are independent indicators of ICC patient prognosis.ConclusionHyperactivated CD47/SIRPα and PD1/PD‐L1 signals in CD68+ TAMs in tumor tissues are negative prognostic markers for ICCs after resection. Furthermore, anti-CD47 in combination with anti-PD1 or CD47/PD1 bispecific antibody (BsAb) may represent promising treatments for ICC. Further studies are also required in the future to confirmed our findings.

01 Dec 2020·Journal of NanobiotechnologyQ2 · ENGINEERING & TECHNOLOGY

Preclinical development of a novel CD47 nanobody with less toxicity and enhanced anti-cancer therapeutic potential

Q2 · ENGINEERING & TECHNOLOGY

ArticleOA

Author: Zhang, Siyuan ; Ma, Linlin ; Wan, Yakun ; Chang, Qing ; Li, Guanghui ; Cao, Longlong ; Qiao, Peng ; Zhu, Min ; Chen, Wanqing ; Gai, Junwei

AbstractBackgroundCD47, the integrin-related protein, plays an important role in immune resistance and escape of tumor cells. Antibodies blocking the CD47/SIRPα signal pathway can effectively stimulate macrophage-mediated phagocytosis of tumor cells, which becomes a promising approach for tumor immunotherapy. Nanobodies (Nbs) derived from camelid animals are emerging as a new force in antibody therapy.ResultsHuNb1-IgG4, an innovative anti-CD47 nanobody, was developed with high affinity and specificity. It effectively enhanced macrophage-mediated phagocytosis of tumor cells in vitro and showed potent anti-ovarian and anti-lymphoma activity in vivo. Importantly, HuNb1-IgG4 did not induce the agglutination of human red blood cells (RBCs) in vitro and exhibited high safety for hematopoietic system in cynomolgus monkey. In addition, HuNb1-IgG4 could be produced on a large scale in CHO-S cells with high activity and good stability. Also, we established anti-CD47/CD20 bispecific antibody (BsAb) consisted of HuNb1 and Rituximab, showing more preference binding to tumor cells and more potent anti-lymphoma activity compared to HuNb1-IgG4.ConclusionsBoth of HuNb1-IgG4 and anti-CD47/CD20 BsAb are potent antagonists of CD47/SIRPα pathway and promising candidates for clinical trials.

News (Medical) associated with Anti-CD47/ICAM-1 bispecific antibody (Virtuoso Therapeutics)

11 Apr 2023

·www.prnewswire.com

Virtuoso Therapeutics to Present Preclinical Findings on Three Best-in-Class Bispecific and ADC Programs at the 2023 American Association for Cancer Research (AACR) Annual Meeting

SAN MATEO, Calif., April 11, 2023 /PRNewswire/ -- Virtuoso Therapeutics, Inc., a private oncology-focused company developing novel bispecific antibodies today announced that it will present three posters highlighting the preclinical data from leading bispecific antibody and ADC programs at the American Associate for Cancer Research (AACR) 2023 Annual Meeting. The details of the Company's presentations at the AACR are as follows: Poster Presentation #1870: Title: VBI–003, a CD47xEpCAM bispecific antibody as a potential treatment for colorectal and small cell lung cancers Session Category: Immunology Session Title: Therapeutic Antibodies 1 Presenting Author: Oi Kwan Wong, Ph.D., Senior Director, Translational Biology Date/Time: April 17th 9:00AM-12:30PM Location: Section 25 Poster Presentation #6334: Title: VBI-002, a CD47xICAM-1 bispecific antibody for the treatment of hepatocellular carcinoma, melanoma and non-small cell lung cancers Session Category: Immunology Session Title: Anticancer Immunotherapeutics Presenting Author: Oi Kwan Wong, Ph.D., Senior Director, Translational Biology Date/Time: April 19th 9:00AM-12:30PM L ocation: Section 22 Poster Presentation #6298: Title: A novel topoisomerase I inhibitor based anti-ICAM–1 antibody drug conjugate for the treatment of hematologic malignancies and solid tumors Session Category: Experimental and Molecular Therapeutics Session Title: Growth Factor Receptors as Therapeutic Targets Presenting Author: Oi Kwan Wong, Ph.D., Senior Director, Translational Biology Date/Time: April 19th 9:00AM-12:30PM L ocation: Section 21 "We believe that our best-in-class CD47 bispecific antibodies confer greater tumor selectivity without sacrificing potency and efficacy. They have been optimized and are ready to begin IND enabling studies," said Sofie Qiao, PhD, President and CEO of Virtuoso Therapeutics. Posters will be available at after the meeting. About Virtuoso Therapeutics, Inc. Virtuoso Therapeutics is an oncology-focused company developing novel bispecific antibodies. The team's expertise and insights could address some of the fundamental challenges of these modalities, such as efficacy and therapeutic window. By applying Virtuoso's technology and know-how, the bispecific programs are highly differentiated and have the potential to achieve a unique product profile. For more information, please visit . Contact Information Sofie Qiao, Ph.D. President and CEO [email protected] 650.666.2753 SOURCE Virtuoso Therapeutics

AACRImmunotherapy

100 Deals associated with Anti-CD47/ICAM-1 bispecific antibody (Virtuoso Therapeutics)

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Hematologic Neoplasms	Preclinical	US	Virtuoso Therapeutics, Inc.	23 Mar 2022
Solid tumor	Preclinical	US	Virtuoso Therapeutics, Inc.	23 Mar 2022

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Anti-CD47/ICAM-1 bispecific antibody (Virtuoso Therapeutics)

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