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Cancer Cell‐targeted and Activatable Photoimmunotherapy Spares T Cells in a 3D Coculture Model
Author(s) -
Kercher Eric M.,
Nath Shubhankar,
Rizvi Imran,
Spring Bryan Q.
Publication year - 2019
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/php.13153
Subject(s) - immune system , cancer research , tumor microenvironment , cancer , photodynamic therapy , cancer cell , immunotherapy , t cell , cell , medicine , immunology , chemistry , biochemistry , organic chemistry
Photodynamic therapy ( PDT ) is an established therapeutic modality that uses nonionizing near‐infrared light to activate photocytotoxicity of endogenous or exogenous photosensitizers ( PS s). An ongoing avenue of cancer research involves leveraging PDT to stimulate antitumor immune responses; however, these effects appear to be best elicited in low‐dose regimens that do not provide significant tumor reduction using conventional, nonspecific PS s. The loss of immune enhancement at higher PDT doses may arise in part from indiscriminate damage to local immune cell populations, including tumor‐infiltrating T cells. We previously introduced “tumor‐targeted, activatable photoimmunotherapy” (ta PIT ) using molecular‐targeted and cell‐activatable antibody– PS conjugates to realize precision tumor photodamage with microscale fidelity. Here, we investigate the immune cell sparing effect provided by ta PIT in a 3D model of the tumor immune microenvironment. We report that high‐dose ta PIT spares 25% of the local immune cell population, five times more than the conventional PDT regimen, in a 3D coculture model incorporating epithelial ovarian cancer cells and T cells. These findings suggest that the enhanced selectivity of ta PIT may be utilized to achieve local tumor reduction with sparing of intratumor effector immune cells that would otherwise be lost if treated with conventional PDT .