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Liora Schultz, MD

Specialties

Hematology/Oncology

Hematology-Oncology

Work and Education

Professional Education

University of Toronto, Toronto, Ontario, Canada, 6/6/2007

Internship

New York Presbyterian Hospital- Weill Cornell, New York, NY, 6/30/2008

Residency

New York Presbyterian Hospital- Weill Cornell, New York, NY, 6/30/2010

Fellowship

Memorial Sloan Kettering Cancer Center, New York, NY, 6/30/2013

Board Certifications

Pediatric Hematology-Oncology, American Board of Pediatrics

Pediatrics, American Board of Pediatrics

Conditions Treated

Acute Leukemia

Graft-Versus-Host Disease

Immune Reconstitiution

Stem Cell Transplant

All Publications

Summary of COVID-19 clinical practice adjustments across select institutions PEDIATRIC BLOOD & CANCER Schultz, L., Link, M. P., Rheingold, S., Hawkins, D. S., Dome, J. S., Wickiser, J., Kung, A. L., Henderson, T. O., Aftandilian, C. 2020

View details for DOI 10.1002/pbc.28411

View details for Web of Science ID 000549825100001

Chimeric Antigen Receptor T Cell Therapy for Pediatric B-ALL: Narrowing the Gap Between Early and Long-Term Outcomes. Frontiers in immunology Schultz, L. 2020; 11: 1985

Abstract

Chimeric Antigen Receptor (CAR) T cell therapy targeting CD19 has introduced a paradigmatic shift in our treatment approach for advanced B cell malignancies. A major advance has been in the field of pediatric B-ALL where complete responses have been achieved across clinical trials with rates of 65-90% in the relapsed/refractory setting. These striking early response rates led to FDA approval of Tisagenlecleucel, CD19-specific CAR T cells, in August 2017. With broadened access and available longitudinal follow up, it is imperative to study the true durability of CAR-mediated responses and establish long-term relapse free and survival outcomes following CAR therapy. Phase I and II clinical trials have reported event-free survival rates of 50% at 1 year following CD19-CAR infusion in children and young adults with B-ALL. Here, we review some of the major challenges accounting for the discrepancy between early response rates and long term outcomes. In specific, relapse with CD19+ or CD19- disease has emerged as a major challenge following CD19-CAR T cell therapy. Related, is the issue of CAR persistence which has been shown to correlate with long-term outcomes. We highlight select efforts to optimize clinical strategies and CAR design to promote enhanced persistence. To date, we do not have robust predictors of response durability and relapse following CAR therapy. The ability to identify patients at risk of relapse in an a priori manner may introduce an interventional window to consolidate CAR-mediated remissions and enhance response durability. This review highlights the need to bridge the gap between the remarkable early complete responses achieved with CD19-CAR T cell therapy and the long-term survival outcomes.

View details for DOI 10.3389/fimmu.2020.01985

View details for PubMedID 32849662

Driving CAR T cell translation forward. Science translational medicine Schultz, L., Mackall, C. 2019; 11 (481)

Abstract

Successes in CAR T cell translation have propelled their commercial launch, but expanding the impact of cancer immunotherapies remains challenging.

View details for PubMedID 30814337

Acute myeloid leukemia immunopeptidome reveals HLA presentation of mutated nucleophosmin. PloS one Narayan, R., Olsson, N., Wagar, L. E., Medeiros, B. C., Meyer, E., Czerwinski, D., Khodadoust, M. S., Zhang, L., Schultz, L., Davis, M. M., Elias, J. E., Levy, R. 2019; 14 (7): e0219547

Abstract

Somatic mutations in cancer are a potential source of cancer specific neoantigens. Acute myeloid leukemia (AML) has common recurrent mutations shared between patients in addition to private mutations specific to individuals. We hypothesized that neoantigens derived from recurrent shared mutations would be attractive targets for future immunotherapeutic approaches. Here we sought to study the HLA Class I and II immunopeptidome of thirteen primary AML tumor samples and two AML cell lines (OCI-AML3 and MV4-11) using mass spectrometry to evaluate for endogenous mutation-bearing HLA ligands from common shared AML mutations. We identified two endogenous, mutation-bearing HLA Class I ligands from nucleophosmin (NPM1). The ligands, AVEEVSLRK from two patient samples and C(cys)LAVEEVSL from OCI-AML3, are predicted to bind the common HLA haplotypes, HLA-A*03:01 and HLA-A*02:01 respectively. Since NPM1 is mutated in approximately one-third of patients with AML, the finding of endogenous HLA ligands from mutated NPM1 supports future studies evaluating immunotherapeutic approaches against this shared target, for this subset of patients with AML.

View details for DOI 10.1371/journal.pone.0219547

View details for PubMedID 31291378

Mechanisms of and approaches to overcoming resistance to immunotherapy. Hematology. American Society of Hematology. Education Program Schultz, L., Gardner, R. 2019; 2019 (1): 22632

Abstract

Immunotherapies have been successfully developed for the treatment of B-cell acute lymphoblastic leukemia (B-ALL) with FDA approval of blinatumomab, inotuzumab, and tisagenlecleucel for relapsed or refractory patients. These agents target either CD19 or CD22, which are both expressed on the surface of the leukemic blasts in the majority of patients. The use of these agents has greatly transformed the landscape of available treatment, and it has provided curative therapy in some patients. As the field has matured, we are learning that for most patients, the currently available immunotherapies are not curative. Leukemic resistance to both CD19 and CD22 pressure has been described and is a major component of developed resistance to these therapies. Patients with B-ALL have developed CD19- or CD22-negative B-ALL, and in more rare cases, they have undergone lineage switch to acute myeloid leukemia. Current efforts are focusing on overcoming antigen escape, either by forced antigen expression or by dual-targeting therapies. A functional immune system is also required for maximal benefit of immunotherapy, particularly with chimeric antigen receptor (CAR) T-cell therapies. Data are now being produced that may allow for the prospective identification of patients whose immune deficits may be identified up front and predict failure. Preclinical work is focusing on additional engineering of CAR T cells to overcome these inherent immune deficits. Last, with improved knowledge of which patients are likely to benefit from immunotherapy as definitive treatment, those patients who are predicted to develop resistance may be prospectively recommended to undergo a consolidative hematopoietic cell transplant to lessen the recurrence risk.

View details for DOI 10.1182/hematology.2019000018

View details for PubMedID 31808880

Organoid Modeling of the Tumor Immune Microenvironment. Cell Neal, J. T., Li, X., Zhu, J., Giangarra, V., Grzeskowiak, C. L., Ju, J., Liu, I. H., Chiou, S., Salahudeen, A. A., Smith, A. R., Deutsch, B. C., Liao, L., Zemek, A. J., Zhao, F., Karlsson, K., Schultz, L. M., Metzner, T. J., Nadauld, L. D., Tseng, Y., Alkhairy, S., Oh, C., Keskula, P., Mendoza-Villanueva, D., De La Vega, F. M., Kunz, P. L., Liao, J. C., Leppert, J. T., Sunwoo, J. B., Sabatti, C., Boehm, J. S., Hahn, W. C., Zheng, G. X., Davis, M. M., Kuo, C. J. 2018; 175 (7): 1972

Abstract

Invitro cancer cultures, including three-dimensional organoids, typically contain exclusively neoplastic epithelium but require artificial reconstitution to recapitulate the tumor microenvironment (TME). The co-culture of primary tumor epithelia with endogenous, syngeneic tumor-infiltrating lymphocytes (TILs) as a cohesive unit has been particularly elusive. Here, an air-liquid interface (ALI) method propagated patient-derived organoids (PDOs) from >100 human biopsies or mouse tumors in syngeneic immunocompetent hosts as tumor epithelia with native embedded immune cells (T, B, NK, macrophages). Robust droplet-based, single-cell simultaneous determination of gene expression and immune repertoire indicated that PDO TILs accurately preserved the original tumor Tcell receptor (TCR) spectrum. Crucially, human and murine PDOs successfully modeled immune checkpoint blockade (ICB) with anti-PD-1- and/or anti-PD-L1 expanding and activating tumor antigen-specific TILs and eliciting tumor cytotoxicity. Organoid-based propagation of primary tumor epithelium en bloc with endogenous immune stroma should enable immuno-oncology investigations within the TME and facilitate personalized immunotherapy testing.

View details for PubMedID 30550791

1 Study of CD19/CD22 Bispecific Chimeric Antigen Receptor (CAR) Therapy in Children and Young Adults with B Cell Acute Lymphoblastic Leukemia (ALL) Schultz, L. M., Davis, K. L., Baggott, C., Chaudry, C., Marcy, A., Mavroukakis, S., Sahaf, B., Kong, K. A., Muffly, L. S., Kim, S., Meyer, E. H., Fry, T. J., Qin, H., Miklos, D. B., Mackall, C. L. AMER SOC HEMATOLOGY. 2018
T-cell immunopeptidomes reveal cell subtype surface markers derived from intracellular proteins. Proteomics Olsson, N., Schultz, L. M., Zhang, L., Khodadoust, M. S., Narayan, R., Czerwinski, D. K., Levy, R., Elias, J. E. 2018

Abstract

Immunopeptidomes promise novel surface markers as ideal immunotherapy targets, but their characterization by mass spectrometry (MS) remains challenging. Until recently, cell numbers exceeding 109were needed to survey thousands of HLA ligands. Such limited analytical sensitivity has historically constrained the types of clinical specimens that can be evaluated to cell cultures or bulk tissues. Measuring immunopeptidomes from purified cell subpopulations would be preferable for many applications, particularly those evaluating rare, primary hematopoietic cell lineages. Here, we test the feasibility of immunopeptidome profiling from limited numbers of primary purified human regulatory T cells (TReg), conventional T cells (Tconv) and activated T cells. The combined T-cell immunopeptide dataset reported here contains 13,804 unique HLA ligands derived from 5,049 proteins. Of these, more than 700 HLA ligands were derived from 82 proteins that we exclusively identified from TReg-enriched cells. This study 1) demonstrates that primary, lineage-enriched T cell supbopulations recovered from single donors are compatible with immunopeptidome analysis; 2) presents new TReg-biased ligand candidates; and 3) supports immunopeptidome surveys value for revealing T cell biology that may not be apparent from expression data alone. Taken together, these findings open up new avenues for targeting TRegand abrogating their suppressive functions to treat cancer. This article is protected by copyright. All rights reserved.

View details for DOI 10.1002/pmic.201700410

View details for PubMedID 29493099

New developments in immunotherapy for pediatric solid tumors. Current opinion in pediatrics Schultz, L. M., Majzner, R., Davis, K. L., Mackall, C. 2017

Abstract

Building upon preclinical advances, we are uncovering immunotherapy strategies that are translating into improved outcomes in tumor subsets. Advanced pediatric solid tumors carry poor prognoses and resultant robust efforts to apply immunotherapy advances to pediatric solid tumors are in progress. Here, we discuss recent developments in the field using mAb and mAb-based therapies including checkpoint blockade and chimeric antigen receptors (CARs).The pediatric solid tumor mAb experience targeting the diganglioside, GD2, for patients with neuroblastoma has been the most compelling to date. GD2 and alternative antigen-specific mAbs are now being incorporated into antibody-drug conjugates, bispecific antibodies and CARs for treatment of solid tumors. CARs in pediatric solid tumors have not yet achieved comparative responses to the hematologic CAR experience; however, novel strategies such as bispecific targeting, intratumoral administration and improved understanding of T-cell biology may yield enhanced CAR-efficacy. Therapeutic effect using single-agent checkpoint blocking antibodies in pediatric solid tumors also remains limited to date. Combinatorial strategies continue to hold promise and the clinical effect in tumor subsets with high antigenic burden is being explored.Pediatric immunotherapy remains at early stages of translation, yet we anticipate that with advanced technology, we will achieve widespread, efficacious use of immunotherapy for pediatric solid tumors.

View details for DOI 10.1097/MOP.0000000000000564

View details for PubMedID 29189429

T-cell-based Immunotherapy: Adoptive Cell Transfer and Checkpoint Inhibition. Cancer immunology research Houot, R., Schultz, L. M., Marabelle, A., Kohrt, H. 2015; 3 (10): 1115-1122

View details for DOI 10.1158/2326-6066.CIR-15-0190

View details for PubMedID 26438444