Abstract 4244
Background
We recently conducted an open- label, single-center, prospective randomized Phase II clinical trial for HLA-A2+ patients with advanced-stage melanoma (NCT01876212) at the University of Pittsburgh Hillman Cancer Center. Patients received ID injections of Type-1-polarized, autologous DC loaded with a mixture of peptides derived from six tumor-associated vascular antigens (DLK1, EPHA2, HBB, NRP1, RGS5, TEM1) combined +/- daily oral administration of dasatinib (70 mg BID) as an immune adjuvant/conditioning agent. Here we report an exploratory analysis of T cell repertoire profiling of longitudinally-sampled peripheral blood leukocytes (PBL) to define potential pharmacodynamic and response biomarkers.
Methods
Total RNA was extracted from pre- and post-treatment PBL from 13 therapy recipients (6 responders, 7 non-Responders) including extended longitudinal samples for four responders. TCRB sequencing was performed via the Oncomine TCRB-LR assay using 25ng total RNA as input. We evaluated T cell clonal expansion and TCR convergence as potential biomarkers of response.
Results
TCR convergence values were elevated in pretreatment PBL of responders compared to non-responders (mean frequency .012 vs .006; p=.01, Wilcoxon), and remained elevated in responders up to 25 weeks post treatment. TCR evenness (normalized Shannon entropy) decreased at week 5 compared to baseline (p=.01, one-sided student’s t-test), indicating increased clonal expansion following treatment.
Conclusions
These data suggest that peripheral blood TCRB convergence may serve as a predictive or prognostic biomarker for response to dendritic cell-based immunotherapy. Our finding of increased T cell clonal expansion at week 5 of treatment supports the notion that TCR sequencing may serve as a tool for the measurement of pharmacodynamic markers of therapeutic agent activity. Ongoing and future studies will further clarify the utility of TCR convergence and clonal expansion as immune repertoire biomarkers.
Clinical trial identification
NCT01876212.
Editorial acknowledgement
Legal entity responsible for the study
University of Pittsburgh School of Medicine & Hillman Cancer Center.
Funding
Thermo Fisher Scientific.
Disclosure
L. Quagliata: Full / Part-time employment: Thermo Fisher Scientific. T. Looney: Full / Part-time employment: Thermo Fisher Scientific. D. Topacio-Hall: Full / Part-time employment: Thermo Fisher Scientific. G. Lowman: Full / Part-time employment: Thermo Fisher Scientific. All other authors have declared no conflicts of interest.
Resources from the same session
5368 - Durvalumab and Paclitaxel Combination for treatment of metastatic triple negative breast cancer is safe with very promising efficacy
Presenter: Hazem Ghebeh
Session: Poster Display session 3
Resources:
Abstract
1520 - A prospective cohort study on the pharmacokinetics of nivolumab in metastatic non-small cell lung cancer, melanoma, and renal cell cancer patients
Presenter: Daan Hurkmans
Session: Poster Display session 3
Resources:
Abstract
1603 - Safety and clinical activity of subcutaneously (SC) administered anti-PD-1 antibody PF-06801591 in phase I dose-expansion cohorts of locally advanced or metastatic non-small-cell lung cancer (NSCLC) and urothelial carcinoma (UC)
Presenter: Byoung Cho
Session: Poster Display session 3
Resources:
Abstract
3922 - Development of the Functional Assessment of Cancer Therapy-Immune Checkpoint Modulator (FACT-ICM): A scale to measure quality of life in cancer patients treated with ICMs
Presenter: Aaron Hansen
Session: Poster Display session 3
Resources:
Abstract
2408 - Immune checkpoint inhibitors (ICIs) as “chemotherapy (Ctx) sensitization” strategy in advanced solid tumors
Presenter: Francisco Javier Ros Montana
Session: Poster Display session 3
Resources:
Abstract
3612 - Validation of progression-free survival (PFS) as surrogate endpoint in randomised trials of immune checkpoint inhibitors in advanced solid cancers
Presenter: Peey Sei Kok
Session: Poster Display session 3
Resources:
Abstract
3827 - Pharmacokinetic (PK) analysis of weight-based and fixed dose cemiplimab in patients (pts) with advanced malignancies
Presenter: Michael Migden
Session: Poster Display session 3
Resources:
Abstract
2120 - A burst of highly differentiated CD4 TL identifies a subset of fast progressors, and correlates with hyperprogressive disease in NSCLC patients treated with ICI
Presenter: Hugo Arasanz
Session: Poster Display session 3
Resources:
Abstract
4254 - Nivolumab treatment in advanced non-small cell lung cancer (aNSCLC): a French nationwide retrospective cohort (UNIVOC Study)
Presenter: Christos Chouaid
Session: Poster Display session 3
Resources:
Abstract
1084 - Dissociated responses in patients with metastatic solid tumors treated with immunotherapy
Presenter: Pauline Vaflard
Session: Poster Display session 3
Resources:
Abstract