Dr. Smith, a Baltimore, MD native, completed her doctoral work at the University of Pittsburgh School of Medicine under the direction of Dr. Charles R. Rinaldo with a focus on T cell immunology and immunotherapy. During her fellowship training at Johns Hopkins, she worked under the mentorship of Dr. Drew M. Pardoll identifying the correlates of response to anti-PD-1 immunotherapy in patients with multiple tumor histologies with a specific emphasis on early and advanced-stage non-small cell lung cancer. She joined the faculty in early 2016 and has since collaborated with many clinicians within Johns Hopkins and at outside institutions on immunotherapy clinical trials aimed at improving treatment options, preventing disease recurrence, and understanding the predictors of response to treatment in both early and advanced-stage disease.
Dr. Smith’s group has developed a novel patent-pending technique to detect and monitor anti-tumor T cells using a simple liquid biopsy approach. This technique, termed MANAFEST (mutation associated neoantigen functional expansion of specific T-cells), is being used in 8 clinical trials and at 5 different research institutions and biotech companies to monitor responses to mutation associated neoantigens, endogenous retroviruses, tumor associated antigens, and viral antigens. This approach has been used to identify neoantigen-specific responses in lung cancer patients with acquired resistance to checkpoint blockade and in colorectal cancer patients with durable clinical benefit to anti-PD-1. More recently, this approach was able to show for the first time that neoantigen-specific T cells are amplified in the periphery following neoadjuvant PD-1 blockade and that these responses may facilitate tumor regression and prevent relapse after surgical resection. Ongoing work includes linking the MANAFEST assay with single cell sequencing technologies to ascertain the intratumoral phenotype of anti-tumor T cells, with a specific interest in how checkpoint blockade treatment regimens augment anti-tumor immunity. This work will elucidate prognostic biomarkers of response and resistance to checkpoint blockade and will help stratify patients most likely to benefit from these treatments.