Justina X. Caushi
A5085068204- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cancer Genomics and Diagnostics
- Immune Cell Function and Interaction
- Immune cells in cancer
- Monoclonal and Polyclonal Antibodies Research
- Cancer Cells and Metastasis
- Advanced biosensing and bioanalysis techniques
- SARS-CoV-2 and COVID-19 Research
- vaccines and immunoinformatics approaches
- T-cell and B-cell Immunology
- Single-cell and spatial transcriptomics
- COVID-19 Clinical Research Studies
- Cancer Research and Treatments
- Bioinformatics and Genomic Networks
- Gene expression and cancer classification
- Protein Degradation and Inhibitors
- Ferroptosis and cancer prognosis
- Genetics, Bioinformatics, and Biomedical Research
- CRISPR and Genetic Engineering
- Cytomegalovirus and herpesvirus research
- Lung Cancer Diagnosis and Treatment
- Lung Cancer Treatments and Mutations
- Lymphoma Diagnosis and Treatment
Johns Hopkins University
2017-2023
Sidney Kimmel Comprehensive Cancer Center
2017-2023
Bloomberg (United States)
2018-2023
Johns Hopkins Medicine
2019-2022
University of Baltimore
2019-2022
Sidney Kimmel Cancer Center
2019
Novartis (Switzerland)
2017
Novartis Institutes for BioMedical Research
2017
Antibodies that block programmed death 1 (PD-1) protein improve survival in patients with advanced non-small-cell lung cancer (NSCLC) but have not been tested resectable NSCLC, a condition which little progress has made during the past decade.In this pilot study, we administered two preoperative doses of PD-1 inhibitor nivolumab adults untreated, surgically early (stage I, II, or IIIA) NSCLC. Nivolumab (at dose 3 mg per kilogram body weight) was intravenously every 2 weeks, surgery planned...
Abstract PD-1 blockade unleashes CD8 T cells 1 , including those specific for mutation-associated neoantigens (MANA), but factors in the tumour microenvironment can inhibit these cell responses. Single-cell transcriptomics have revealed global dysfunction programs tumour-infiltrating lymphocytes (TIL). However, majority of TIL do not recognize antigens 2 and little is known about transcriptional MANA-specific TIL. Here, we identify clones using MANA functional expansion assay 3 neoadjuvant...
Abstract Mutation-associated neoantigens (MANA) are a target of antitumor T-cell immunity. Sensitive, simple, and standardized assays needed to assess the repertoire functional MANA-specific T cells in oncology. Assays analyzing vitro cytokine production such as ELISpot intracellular staining have been useful but limited sensitivity assessing tumor-specific responses do not analyze antigen-specific repertoires. The FEST (Functional Expansion Specific cells) assay described herein integrates...
BACKGROUND. Recent studies have reported T cell immunity to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in unexposed donors, possibly due crossrecognition by cells specific for common cold coronaviruses (CCCs). True crossreactivity, defined as recognition a single TCR of more than one distinct peptide-MHC ligand, has never been shown context SARS-CoV-2.
Regulatory T cells (T reg ) are conventionally viewed as suppressors of endogenous and therapy-induced antitumor immunity; however, their role in modulating responses to immune checkpoint blockade (ICB) is unclear. In this study, we integrated single-cell RNA-seq/T cell receptor sequencing (TCRseq) >73,000 tumor-infiltrating (TIL-T from anti–PD-1–treated treatment-naive non–small lung cancers (NSCLC) with analysis tumor-associated antigen (TAA)–specific derived a murine tumor model. We...
Transcription factors ThPOK and Runx3 regulate the differentiation of “helper” CD4+ “cytotoxic” CD8+ T cell lineages respectively, inducing single positive (SP) cells that enter periphery with expression either CD4 or CD8 co-receptor. Despite expectation these fates are mutually exclusive mature CD4+CD8+ double (DP) present in healthy individuals augmented context disease, yet their molecular features pathophysiologic role disputed. Here, we show DP murine human tumors as a heterogenous...
COVID-19 mRNA vaccines elicit strong T and B cell responses to the SARS-CoV-2 spike glycoprotein in both naïve experienced patients. However, it is unknown whether post-vaccine CD4+ seen patients with a history of are due restimulation clonotypes that were first activated during natural infection or if they result new clones by vaccine.
Abstract Oncogenic driver mutations in p53 occur frequently cancer. T cell engagers that specifically target tumor cells harboring have the potential to enable durable efficacy while sparing normal tissue. CLSP-1025 leverages this specificity by targeting tumors express R175H mutant protein HLA-A*02:01 positive patients. The preclinical characterization provides a foundation for advancing first-in-human (FIH) study.CLSP-1025 is half-life extended single-chain diabody IgG4 Fc fusion binds...
8524 Background: Improved therapy is needed for patients (pts) with early-stage non-small cell lung cancer (NSCLC), as the majority relapse after curative resection. Our group reported first trial of neoadjuvant PD-1 blockade in resectable NSCLC, finding to be safe and feasible. Here we report extended clinical follow-up long-term molecular response data from this trial. Methods: IV nivolumab 3 mg/kg was given every 2 weeks doses prior surgery 20 pts NSCLC at Johns Hopkins MSKCC. Blood...
Abstract Background: Programmed death-1 (PD-1) blocking antibodies improve survival in patients with advanced non-small-cell lung cancer (NSCLC) but have not been tested resectable NSCLC, where little progress has made over the last decade. Methods: Adults untreated surgically stage I-IIIA NSCLC received two doses of nivolumab (anti-PD-1) preoperatively. The primary endpoints study were safety and feasibility. Tumor pathologic response, PD-L1 expression, mutation burden mutation-associated...
<h3>Background</h3> CLSP-1025 is a T-cell engager (TCE) designed to treat p53 R175H mutant tumors in patients who are positive for HLA-A*02:01. an asymmetric bispecific single-chain diabody (scDb) Fc fusion protein with monovalent binding specific the p53(R175H)<sub>168–176</sub> peptide bound HLA-A*02:01 on cancer cells and CD3ε T cells. The anti-peptide HLA (pHLA) variable domain of was specifically developed recognize presenting ignore wild-type p53<sub>168–176</sub> peptide.<sup>1</sup>...
<h3>Background</h3> PD-1/PD-L1 pathway blockade has improved survival in patients with advanced NSCLC. Neoadjuvant (pre-operative) anti-PD-1 plus chemotherapy was also recently approved for resectable stage II/III However, among receiving neoadjuvant anti-PD-1-based therapy, only 33–45% achieved a major pathologic response (MPR, ≤10% of residual viable tumor), highlighting the need biomarkers predicting response.<sup>1,3</sup> Based upon recent results melanoma showing that CD8+FoxP3+ cells...
<h3>Background</h3> Mutation-associated neoantigen (MANA)-specific T cells play a key role in tumor control and response to immune checkpoint inhibition (ICI).<sup>1 2</sup> However, the majority of tumor-infiltrating lymphocytes (TIL) are not specific for tumor.<sup>3</sup> Herein, we developed validated MANAscore, bioinformatic scoring algorithm based on transcriptional programs MANA-specific isolate antitumor from bystander lung cancer melanoma. <h3>Methods</h3> Combined single-cell (sc)...
Abstract Recent advances in next-generation sequencing have revealed the presence of genetic heterogeneity and clonal evolution within tumors. Intratumoral has been implicated disease progression, metastasis, therapeutic responses development drug resistance. Although cancer cell line xenograft models extensively used research to test efficacy, it is unknown how much maintained process establishment. In order quantitatively assess complexity models, here we applied a cellular barcoding...
Abstract Targeted therapies, such as erlotinib and imatinib, lead to dramatic clinical responses, but the emergence of resistance presents a significant challenge. Recent studies have revealed intratumoral heterogeneity potential source for therapeutic resistance. However, it is still unclear if relapse/resistance driven predominantly by pre-existing or de novo acquired alterations. To address this question, we developed high-complexity barcode library, ClonTracer, which contains over 27...
<p>Figures S1-S8</p>
<p>Clinical and genomic data for patients included in our study</p>