Cell therapies have emerged as a promising therapeutic modality with the potential to treat and even cure a diverse array of diseases. Cell therapies offer unique clinical and therapeutic advantages over conventional small molecules and the growing number of biologics. Particularly, living cells can simultaneously and dynamically perform complex biological functions in ways that conventional drugs cannot; cell therapies have expanded the spectrum of available therapeutic options to include key cellular functions and processes. As such, cell therapies are currently one of the most investigated therapeutic modalities in both preclinical and clinical settings, with many products having been approved and many more under active clinical investigation. Here, we highlight the diversity and key advantages of cell therapies and discuss their current clinical advances. In particular, we review 28 globally approved cell therapy products and their clinical use. We also analyze >1700 current active clinical trials of cell therapies, with an emphasis on discussing their therapeutic applications. Finally, we critically discuss the major biological, manufacturing, and regulatory challenges associated with the clinical translation of cell therapies.

Skin cancer is one of the most common types of cancer in the United States and worldwide. Topical products are effective for treating cancerous skin lesions when surgery is not feasible. However, current topical products induce severe irritation, light-sensitivity, burning, scaling, and inflammation. Using hyaluronic acid (HA), we engineered clinically translatable polymer-drug conjugates of doxorubicin and camptothecin termed, DOxorubicin and Camptothecin Tailored at Optimal Ratios (DOCTOR) for topical treatment of skin cancers. When compared to the clinical standard, Efudex, DOCTOR exhibited high cancer-cell killing specificity with superior safety to healthy skin cells. In vivo studies confirmed its efficacy in treating cancerous lesions without irritation or systemic absorption. When tested on patient-derived primary cells and live-skin explants, DOCTOR killed the cancer with a selectivity as high as 21-fold over healthy skin tissue from the same donor. Collectively, DOCTOR provides a safe and potent option for treating skin cancer in the clinic.

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Skin cancer is the most common class of malignancies in humans with increasing incidence worldwide. Although surgery remains the most common treatment approach, relapses after surgery necessitate other treatment options. There is an increasing clinical demand for topical treatments for skin cancer that can improve the drug's cutaneous localization while limiting systemic absorption. In this study, hyaluronic acid (HA) conjugates are successfully synthesized by attaching a third-generation retinoid (bexarotene) and a histone deacetylase inhibitor (vorinostat) to HA via ester bonds. The conjugates are characterized to ensure identity and quantify total drug loading. HA-BEX and HA-VOR exhibit a synergistic anticancer effect against human squamous cell carcinoma (A431) and human cutaneous T cell lymphoma cell lines (HUT 78) at specific ratios with minimal adverse effect on primary human keratinocytes and fibroblasts. Confocal microscopy demonstrates localization of the conjugates inside the cancer cells. Ex vivo skin permeation studies on human skin explants confirm their ability to penetrate the stratum corneum and reach the deep dermis. Biodistribution studies in the skin reveal the presence of both drugs in the epidermis and dermis in amounts sufficient to exert inhibitory effect on cancer cells. HA-bexarotene-vorinostat conjugates offer an excellent therapeutic option to treat skin cancers.