Advances in the study of <scp>CD47</scp>‐based bispecific antibody in cancer immunotherapy

Zhang, Binglei; Li, Wei; Fan, Dandan; Tian, Wenzhi; Zhou, Jingming; Ji, Zhenyu; Song, Yongping

doi:10.1111/imm.13498

Cited by 18 publications

(14 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The China Drug Clinical Trial and Information Disclosure Platform ( http://www.chinadrugtrials.org.cn/ ) presents more than 80 BsAbs, while a clinical trial website platform ( https://clinical.trials.gov/ ) showcases more than 200. Among them, BsAbs targeting the CD47/SIRPα axis are the main research focus [ 154 ]. Anti-CD47/SIRPα BsAbs are classified according to the antigen that they target; thus, they can be classified as BsAbs targeting tumor antigens (PD-L1, CD20, CD19, mesothelin [MSLN], Claudin18.2, and Her2), BsAbs targeting immune cells (PD-1, CD40, and 41BB), BsAbs targeting cytokines or receptors (CSF-2 receptor/VEGF), and BsAbs targeting cytokines or receptors (CSF-2 receptor/VEGF) among others.…”

Section: Strategies For Targeting Macrophages In the Treatment Of Sol...mentioning

confidence: 99%

Targeting macrophages: a novel treatment strategy in solid tumors

Liu

Song

et al. 2022

J Transl Med

Self Cite

View full text Add to dashboard Cite

In the tumor microenvironment (TME), tumor-associated macrophages (TAMs) are the most abundant immune cells, which act as a key regulator in tumorigenesis and progression. Increasing evidence have demonstrated that the TME alters the nature of macrophages to maintain dynamic tissue homeostasis, allowing TAMs to acquire the ability to stimulate angiogenesis, promote tumor metastasis and recurrence, and suppress anti-tumor immune responses. Furthermore, tumors with high TAM infiltration have poor prognoses and are resistant to treatment. In the field of solid tumor, the exploration of tumor-promoting mechanisms of TAMs has attracted much attention and targeting TAMs has emerged as a promising immunotherapeutic strategy. Currently, the most common therapeutic options for targeting TAMs are as follows: the deletion of TAMs, the inhibition of TAMs recruitment, the release of phagocytosis by TAMs, and the reprogramming of macrophages to remodel their anti-tumor capacity. Promisingly, the study of chimeric antigen receptor macrophages (CAR-Ms) may provide even greater benefit for patients with solid tumors. In this review, we discuss how TAMs promote the progression of solid tumors as well as summarize emerging immunotherapeutic strategies that targeting macrophages.

show abstract

Section: Strategies For Targeting Macrophages In the Treatment Of Sol...mentioning

confidence: 99%

Targeting macrophages: a novel treatment strategy in solid tumors

Liu

Song

et al. 2022

J Transl Med

Self Cite

View full text Add to dashboard Cite

show abstract

“…Because of its specificity and bi-function, it has become a research hotspot in the field of antibody engineering and has a broad application prospect in the fields of tumor therapy and autoimmune diseases (34)(35)(36). Compared with the monoclonal antibody, the bispecific antibody has an additional specific antigen-binding site (37), which makes them more specific, more accurate in targeting tumor cells, and less toxic to off-target cells, there are four major advantages of BsAb including (1) BsAb has two antigen-binding sites, which allows them to bridge the tumor cells and immune cells, reorient immune cells, and recruit immune cells to the periphery of tumor cells and enhance the anti-tumor effect (37)(38)(39); (2) BsAb can block/activate two different immune signal pathways downstream at the same time to enhance the cytotoxicity of tumor cells (39); (3) BsAb can bind to two different cell surface antigens and may potentially increase binding specificity and reduce side effects such as off-target (40)(41)(42)(43). ( 4) BsAb offers several benefits in terms of manufacture, preparation, and drug declaration, and it is less expensive than antibody combinations (44,45).…”

Section: Discussionmentioning

confidence: 99%

PD-1/LAG-3 bispecific antibody potentiates T cell activation and increases antitumor efficacy

Shi

Zhou

Liu³

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

Several clinical studies demonstrate that there exist other immune checkpoints overexpressed in some PD-1 inhibitor-resistant tumor patients. Among them, Lymphocyte-activation gene 3 (LAG-3) is one of the important immune checkpoint molecules and has been clinically demonstrated to have synergistic anti-tumor effects in combination with PD-1 antibody. In this study, we designed a novel ‘knob-in-hole’ PD-1/LAG-3 bispecific antibody (BsAb) YG-003D3. In conclusion, the BsAb maintained the similar affinity and thermal stability to the parental antibody, and the BsAb structure can be independent of each other in the process of double-target recognition, and the recognition activity will not be affected. Moreover, the BsAb can not only target PD-1 and LAG-3 on single cell simultaneously, but also bridge the two kinds of cells expressing PD-1 and LAG-3, so as to release the ‘brake system of immune checkpoints’ and activate immune cells to exert anti-tumor effects more effectively. Especially in the PBMCs activation assay, YG-003D3 induced stronger IFN-γ, IL-6, and TNF-α secretion compared to anti-PD-1 or anti-LAG-3 single drug group or even combined drug group. In the tumor killing experiment of PBMC in vitro, YG-003D3 has a better ability to activate PBMC to kill tumor cells than anti-PD-1 or anti-LAG-3 single drug group or even combined drug group, and the killing rate is as high as 20%. In a humanized PD-1/LAG-3 transgenic mouse subcutaneous tumor-bearing model, YG-003D3 showed good anti-tumor activity, even better than that of the combination group at the same molar concentration. Further studies have shown that YG-003D3 could significantly alter the proportion of immune cells in the tumor microenvironment. In particular, the proportion of CD45+, CD3+ T, CD8+ T cells in tumor tissue and the proportion of CD3+ T, CD8+ T, CD4+ T cells in peripheral blood were significantly increased. These results suggest that YG-003D3 exerts a potent antitumor effect by activating the body ‘s immune system. In summary, the BsAb YG-003D3 has good anti-tumor activity, which is expected to become a novel drug candidate for cancer immunotherapy.

show abstract

“…Our group summarized the targeting of macrophage-based BsAbs for cancer therapy. [44,66] In this section, we focus on the use of BsAbs for B-cell lymphoma treatment. The selected ongoing clinical trials of CD47-SIRPα-targeted BsAbs in B-cell lymphoma are presented in Supplementary Table 1, http://links.lww.com/CM9/B795.…”

Section: Targeting Macrophage Bsabsmentioning

confidence: 99%

Immune cells in the B-cell lymphoma microenvironment: From basic research to clinical applications

Zhang,

Liu,

et al. 2024

Chinese Medical Journal

Self Cite

View full text Add to dashboard Cite

B-cell lymphoma is a group of hematological malignancies characterized by variable genetic and biological features and clinical behaviors. The tumor microenvironment (TME) is a complex network in tumors, which consists of surrounding blood vessels, extracellular matrix, immune and non-immune cells, and signaling molecules. Increasing evidence has shown that the TME, especially immune cells within, is a double-edged sword, acting either as a tumor killer or as a promoter of tumor progression. These pro-tumor activities are driven by subpopulations of immune cells that express typical markers but have unique transcriptional characteristics, making tumor-associated immune cells good targets for human anti-cancer therapy by ablating immunosuppressive cells or enhancing immune-activated cells. Thus, exploring the role of immune cells in the TME provides distinct insights for immunotherapy in B-cell lymphoma. In this review, we elucidated the interaction between immune cells and tumor cells and their function in the initiation, progression, and prognosis of B-cell lymphoma, from preclinical experiments to clinical trials. Furthermore, we outlined potential therapeutic approaches and discussed the potential clinical value and future perspectives of targeting immune cells in patients with B-cell lymphoma.

show abstract

Advances in the study of CD47‐based bispecific antibody in cancer immunotherapy

Cited by 18 publications

References 80 publications

Targeting macrophages: a novel treatment strategy in solid tumors

Targeting macrophages: a novel treatment strategy in solid tumors

PD-1/LAG-3 bispecific antibody potentiates T cell activation and increases antitumor efficacy

Immune cells in the B-cell lymphoma microenvironment: From basic research to clinical applications

Contact Info

Product

Resources

About