CRISPR-enhanced engineering of therapy-sensitive cancer cells for self-targeting of primary and metastatic tumors.

Tumor cells engineered to express therapeutic agents have shown promise to treat cancer. However, their potential to target cell surface receptors specific to the tumor site and their posttreatment fate have not been explored. We created therapeutic tumor cells expressing ligands specific to primary and recurrent tumor sites (receptor self-targeted tumor cells) and extensively characterized two different approaches using (i) therapy-resistant cancer cells, engineered with secretable death receptor-targeting ligands for "off-the-shelf" therapy in primary tumor settings, and (ii) therapy-sensitive cancer cells, which were CRISPR-engineered to knock out therapy-specific cell surface receptors before engineering with receptor self-targeted ligands and reapplied in autologous models of recurrent or metastatic disease. We show that both approaches allow high expression of targeted ligands that induce tumor cell killing and translate into marked survival benefits in mouse models of multiple cancer types. Safe elimination of therapeutic cancer cells after treatment was achieved by co-engineering with a prodrug-converting suicide system, which also allowed for real-time in vivo positron emission tomography imaging of therapeutic tumor cell fate. This study demonstrates self-tumor tropism of engineered cancer cells and their therapeutic potential when engineered with receptor self-targeted molecules, and it establishes a roadmap toward a safe clinical translation for different cancer types in primary, recurrent, and metastatic settings.

A clinical and statistical survey of cutaneous changes in the first 120 hours of life.

BACKGROUND: The spectrum of dermatological manifestations during neonatal period varies from transient self-limiting conditions to serious dermatoses; the latter, fortunately few, are disproportionately stressful to the parents, who due to lack of specialized pediatric dermatology clinics frequently get tossed between a dermatologist and a pediatrician. OBJECTIVES: This study was formulated to record cutaneous changes over the first five postnatal days of life and to statistically correlate those changes occurring in ≥ 11 neonates with three (parity, associated illnesses, and mode of delivery) maternal and three (sex, birth weight, and gestational age) neonatal factors. METHODS: This descriptive, cross-sectional study at a tertiary care hospital entailed recording detailed dermatological examination of 300 neonates having some (physiological and/or pathological) cutaneous changes and their statistical evaluation using the Chi-square test and significance (P < 0.05) as above. RESULTS: Superficial cutaneous desquamation (SCD), Mongolian spots (MS), and erythema toxicum neonatorum (ETN) were the first three common changes among a total of 15 conditions observed overall; these three, as also milia and icterus, revealed statistical significance with both maternal as well as neonatal factors. Lanugo and napkin dermatitis (ND) were statistically significant with respect to two neonatal factors and cradle cap (CC), a single maternal factor. Gestational age was of statistical significance regarding five cutaneous changes, associated maternal illness during pregnancy regarding four, birth weight as well as parity regarding three each, and sex of the neonate as well as mode of delivery regarding two each. CONCLUSION: Despite observing a statistically significant correlation of eight cutaneous changes with three maternal and/or three neonatal factors, more extensive studies in neonatal dermatology are required for validation of these unique statistical correlations.