Creative Biolabs has earned unparalleled expertise and great reputation after years of commitment to antibody developing and engineering field. Currently, we proudly present our professional service of apoptosis and programmed cell death assessment as part of our integrated antibody function characterization portfolio.

Apoptosis is a type of programmed cell death (PCD), which is defined as a highly regulated process of cell elimination. Key events of apoptotic cells involve cell shrinking, nuclear and chromosomal fragmentation, PARP cleavage, etc. Two major pathways can elicit cell apoptosis, the intrinsic (or mitochondrial) pathway, and extrinsic (or death receptor) pathway. Given its crucial role in the individual development and homeostasis maintenance of all multicellular organisms, many of the widely-used drugs are intended to interfere with apoptosis process to deliver clinical effects, especially antibodies. Therapeutic antibodies can specifically bind to target cells, either triggering direct killing by apoptosis (e.g. anti-cancer agents) or inhibiting aberrant apoptosis (e.g. neurodegenerative or autoimmune disease therapies). Since apoptosis is a complex, highly dynamic process involving a variety of parameters that overlap with other mechanisms of action, one major key of determining the participation of apoptosis by either intrinsic or extrinsic pathway is to integrate the results of multiple assays. In that effort, Creative Biolabs has established a panel of well-validated assay formats to help our clients better outline the apoptosis MOA of their antibody candidates.

Fig. 1 Morphological and molecular events in apoptosis. (Nössing & Kevin, 2023)Fig. 1 Morphological and molecular events in apoptosis.1

Determine the Exact Mechanism of Cell Death

For exactly what reason that lead to the eventual death of your target cells? Routine proliferation assays cannot provide accurate information of cell death in response to certain antibodies. Creative Biolabs combines three individual assays and builds up a novel analysis system. This triple-endpoint assay is capable of simultaneously evaluate cell viability, cytotoxicity, and apoptosis characteristics, thus allowing more comprehensive data to uncover the exact mechanism.

Apoptosis Screening & Profiling

Extrinsic apoptosis is a complicated process involving various signal transduction pathways and cellular molecules. By interactions with cell surface receptors, antibodies can lead to cell death through activation of a series of compounds, especially caspase family, which is known as the predominant apoptosis factor, and Bcl proteins that directly or indirectly activate the former.

Creative Biolabs has brought together a full range of screening assays to detect and assess apoptosis factors. We can provide standard caspase enzymatic cleavage test by fluorescent or luminescent assays, as well as dose formulation analysis to determine the accurate IC50 value. Our simple, ready-for-use assay system is well-adapted for automated high-throughput format, which covers a bulk of the common apoptosis-related key molecules.

The apoptosis targets we are able to analyze in Creative Biolabs including but not restricted to:

  • Caspase 2
  • Caspase 3/7
  • Caspase 6
  • Caspase 8
  • Caspase 9
  • Bcl-2
  • Bcl-XL

Antibodies can elicit direct cell death, either through apoptosis, or non-apoptotic programmed cell death, such as homotopic cell aggregation, changes in actin reorganization, and lysosomal disruption. One example is the Fc-independent direct killing of B cells by Type II mAbs, such as tositumomab and GA-101. We can also conduct special tests, i.e. FACS staining, to detect similar mechanisms.

PathSpecific™ Apoptosis Assay Service

To keep cancer cells and tumors from multiplying, our bodies have an essential defensive process called apoptosis. A critical way to determine the efficacy of anti-cancer drugs against cancer cells is to measure the activation of apoptosis. Creative Biolabs offers a high-quality, low-cost PathSpecific™ apoptosis assay service that focuses on a number of apoptosis targets, such as caspase, Bcl, cIAP, and others. In addition, we incorporate several approaches into this service, i.e. flow cytometry detection assay, to comprehensively measure apoptosis to meet global customers' drug discovery needs.

With state-of-the-art technical platforms and exceptional expertise in this field, Creative Biolabs guarantees our customers with fast turnaround, high-quality, cost-effectiveness of apoptosis and cell death analysis service. For more detailed information, please feel free to contact us or directly sent us an inquiry.

Reference

  1. Nössing, Christoph, and Kevin M. Ryan. "50 years on and still very much alive:'Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics'." British Journal of Cancer 128.3 (2023): 426-431.

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