Abstract
The recent emergence of engineered cellular therapies, such as Chimeric antigen receptor (CAR) CAR T and T cell receptor (TCR) engineered T cells, has shown great promise in the treatment of various cancers. These agents aggregate and expand exponentially at the tumor site, resulting in potent immune activation and tumor clearance. Moreover, the ability to elaborate these cells with therapeutic agents, such as antibodies, enzymes, and immunostimulatory molecules, presents an unprecedented opportunity to specifically modulate the tumor microenvironment through cell-mediated drug delivery. This unique pharmacology, combined with significant advances in synthetic biology and cell engineering, has established a new paradigm for cells as vectors for drug delivery. Targeted cellular micropharmacies (TCMs) are a revolutionary new class of living drugs, which we envision will play an important role in cancer medicine and beyond. Here, we review important advances and considerations underway in developing this promising advancement in biological therapeutics.
Highlights
A central aim of modern pharmacology is to selectively treat disease while avoiding harmful effects to normal cells, tissues, and systems
Adoptive cell therapy with cytokine-engineered tumor-infiltrating lymphocyte (TIL) could be used to prolong the in vivo survival of transferred cells and minimize the toxicity associated with exogenous cytokine administration [11,12]
Natural killer (NK) cells may be pre-activated with cytokines or engineered with Chimeric antigen receptor (CAR) and are relatively easy to generate from umbilical cord blood, induced pluripotent stem cells, and the NK-92 cell line [34,57,58,59,60,61,62,63,64]
Summary
A central aim of modern pharmacology is to selectively treat disease while avoiding harmful effects to normal cells, tissues, and systems This is an inherently difficult challenge as traditional therapeutic agents are distributed systemically throughout the body and can act indiscriminately. Certain cell types have been evolutionarily optimized to possess several pharmacokinetic properties that pharmacologists still strive to achieve in drug design, such as precise tissue localization, temporal control of action when needed, and rheostats to control activity levels locally. These cells are smarter than current systemically administered agents. Bacteria, exosomes, and other nanoparticles have been described elsewhere and are beyond the scope of this review [7,8,9,10]
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