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Whole-cell therapy is a therapeutic modality where entire living cells are administered to a patient to achieve a medicinal effect, rather than targeting a single molecule or pathway. This approach is often categorized as 'Not Applicable' in traditional target databases because the therapy's efficacy stems from a broad array of paracrine signals and direct cell-to-cell interactions rather than a single lock-and-key molecular mechanism (American Society of Gene & Cell Therapy, 2023). For example, mesenchymal stem cells (MSCs) release a complex secretome of growth factors and anti-inflammatory cytokines to promote tissue healing and suppress pathological inflammation (NIH, 2022). Similarly, adoptive immunotherapies like CAR-T cells involve the infusion of engineered lymphocytes that navigate to and interact with the tumor microenvironment through multiple contact-dependent pathways. Because these 'living drugs' can sense and respond to their environment, they offer a dynamic therapeutic profile that traditional small molecules or biologics cannot replicate. However, this complexity also introduces significant safety challenges, such as the risk of systemic inflammatory responses like cytokine release syndrome and the potential for long-term persistence or transformation of the infused cells (StatPearls, 2023).
Whole-cell therapies function through multi-modal mechanisms including the secretion of paracrine factors such as cytokines, chemokines, and extracellular vesicles (exosomes), as well as direct contact-dependent signaling via surface receptors to modulate the host microenvironment (Galipeau & Sensébé, 2018, Nature Biomedical Engineering). In the case of regenerative cells like MSCs, they may also differentiate into specific cell types or provide a scaffold for tissue repair, while engineered immune cells like CAR-T cells utilize synthetic receptors to recognize and kill target cells directly (June et al., 2018, NEJM).
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