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Immune Cell Engager based Bispecific Antibody (BsAb) Design Services

The immune system is indispensable to human health, playing a vital role in cancer prevention and treatment by naturally orchestrating anti-tumor responses. Exploiting this innate defense, bispecific antibodies (BsAbs) have emerged as a promising therapeutic modality, capable of engaging two or more receptors simultaneously to redirect immune cells toward malignant targets. This retargeting elicits a cascade of events—immune cell activation and proliferation, cytokine secretion, phagocytosis, and ultimately tumor eradication.

Action mechanism of bispecific antibody (bsAb)-based immune-cell engagers (ICEs) in cancers. (OA Literature)Fig.1 Mechanism of BsAb-mediated immune cell engagement in cancer therapy.1, 3

Creative Biolabs, leveraging advanced BsAb engineering and production platforms, delivers bespoke immune cell engager services, including T cell, NK cell, and macrophage targeting constructs, thereby facilitating the rapid development of innovative cancer therapies.

BsAbs for Immune Cell Recruitment

T cells and NK cells represent pivotal cytotoxic lymphocytes integral to immune defense. A range of BsAb formats—including tandem scFv constructs and diabodies—are engineered to enlist these cells by engaging CD3 on T cells or CD16/CD56 on NK cells while simultaneously binding tumor-associated antigens in Creative Biolabs. Moreover, BsAbs harboring an Fc domain facilitate the recruitment of accessory cells such as dendritic cells, NK cells, and macrophages via Fcγ receptor binding. Upon redirection to the tumor milieu, these effector cells unleash cytotoxic and pro-inflammatory cytokines. Meticulous design of these molecules involves selecting antibody affinities that temper Fc-mediated activities while enhancing tumor antigen specificity, thereby optimizing the therapeutic index.

T Cell Engager (TCE) Based BsAb Design Service

Creative Biolabs delivers BsAbs engineered to engage both tumor-associated antigens and the CD3 complex on T cells, thereby reorienting T cells towards malignant targets and initiating cytotoxic responses against cancer cells.

NK Cell Engager (NKCE) Based BsAb Design Service

Creative Biolabs engineers BsAbs that simultaneously engage tumor-associated antigens and NK cell activation receptors, such as CD16A, effectively directing natural killer cells toward malignant cells and initiating NK cell-mediated cytotoxic responses.

Macrophage Engager (ME) Based BsAb Design Service

Engineered BsAbs orient macrophages toward tumor cells by concurrently targeting tumor-associated antigens and activating receptors such as CD32A, thereby promoting macrophage-driven phagocytosis and cytotoxic elimination of malignant cells.

Published Data

Pharmacological properties of T-BsAbs. (OA Literature)Fig.2 Schematic diagram of pharmacological properties of T-cell engaged BsAbs.2, 3

A promising approach to promote T cell infiltration is T cell bispecific antibody (T-BsAb) therapy. These antibodies consist of two antigen-binding domains that recognize a tumor-associated antigen (TAA) on cancer cells and the CD3 subunit associated with the T cell receptor (TCR) on T cells. This dual antigen recognition facilitates the crosslinking of tumor and T cells, enabling T cells to identify cancer cells without MHC involvement. Unlike checkpoint inhibitors that block inhibitory signals to effector T cells, T-BsAbs specifically activate memory T cells, and to a lesser extent, naïve T cells. Consequently, T-BsAbs are believed to redirect host immunity against poorly immunogenic solid tumors, involving T cell recruitment and immunological synapse formation.

Creative Biolabs boasts a highly experienced research team specializing in BsAb technology, underpinned by state‐of‐the‐art antibody engineering platforms. The company delivers personalized services that encompass every aspect of BsAb development—from initial design and engineering through to manufacturing and comprehensive analysis.

References

  1. Shin, Ha Gyeong, et al. "Bispecific antibody-based immune-cell engagers and their emerging therapeutic targets in cancer immunotherapy." International Journal of Molecular Sciences 23.10 (2022): 5686.
  2. Kamakura, Daisuke, Ryutaro Asano, and Masahiro Yasunaga. "T cell bispecific antibodies: an antibody-based delivery system for inducing antitumor immunity." Pharmaceuticals 14.11 (2021): 1172.
  3. Distributed under Open Access license CC BY 4.0, without modification.
Our products and services are for research use only, and not for use in diagnostic or therapeutic procedures.

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