Luis Sanchez-Perez

Overview:

My overall research interests include the elucidation of immune mechanisms underlying the efficacy of novel immunotherapeutic strategies for the treatment of malignant brain tumors. I am currently evaluating the mechanisms of Chimeric Antigen Receptor (CAR) gene-modified T-cells mediated immune tumor cell destruction and the induction of endogenous immunity to individual tumor specific mutations. 

Positions:

Assistant Professor of Neurosurgery

Neurosurgery
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2005

Mayo Graduate School

Postdoctoral Fellow, National Cancer Institute, Surgery Branch

National Institutes of Health

Grants:

EGFRvIII-targeted Bispecific T cell Engagers for brain tumors

Administered By
Neurosurgery
Awarded By
National Institutes of Health
Role
Investigator
Start Date
End Date

A Novel Clinical Challenge in Brain Tumor Immunology: T cell Sequestration

Administered By
Neurosurgery
Awarded By
National Institutes of Health
Role
Investigator
Start Date
End Date

CCL3 as a Developmental Therapeutic to Enhance Brain Tumor Therapy

Administered By
Neurosurgery
Awarded By
National Institutes of Health
Role
Research Scientist
Start Date
End Date

Brain tumors with regulatory T-cells treated with EGFRvIII-specific T-cells

Administered By
Neurosurgery
Awarded By
National Institutes of Health
Role
Research Scientist
Start Date
End Date

A clinically-relevant anti-CD27 agonist antibody as a vaccine adjuvant for brain tumor immunotherapy

Administered By
Neurosurgery
Awarded By
National Institutes of Health
Role
Collaborator
Start Date
End Date

Publications:

Comparative study of α-helical and β-sheet self-assembled peptide nanofiber vaccine platforms: influence of integrated T-cell epitopes.

Several different self-assembling peptide systems that form nanofibers have been investigated as vaccine platforms, but design principles for adjusting the character of the immune responses they raise have yet to be well articulated. Here we compared the immune responses raised by two structurally dissimilar peptide nanofibers, one a β-sheet fibrillar system (Q11), and one an α-helical nanofiber system (Coil29), hypothesizing that integrated T-cell epitopes within the latter would promote T follicular helper (Tfh) cell engagement and lead to improved antibody titers and quality. Despite significantly different internal structures, nanofibers of the two peptides exhibited surprisingly similar nanoscale morphologies, and both were capable of raising strong antibody responses to conjugated peptide epitopes in mice without adjuvant. Both were minimally inflammatory, but as hypothesized Coil29 nanofibers elicited antibody responses with higher titers and avidities against a conjugated model epitope (OVA323-339) and a candidate peptide epitope for vaccination against S. aureus. Subsequent investigation indicated that Coil29 nanofibers possessed internal CD4+ T cell epitopes: whereas Q11 nanofibers required co-assembly of additional CD4+ T cell epitopes to be immunogenic, Coil29 nanofibers did not. Coil29 nanofibers also raised stronger germinal center B cell responses and follicular helper T cell (Tfh) responses relative to Q11 nanofibers, likely facilitating the improvement of the antibody response. These findings illustrate design strategies for improving humoral responses raised by self-assembled peptide nanofibers.
Authors
Wu, Y; Kelly, SH; Sanchez-Perez, L; Sampson, JH; Collier, JH
MLA Citation
URI
https://scholars.duke.edu/individual/pub1442183
PMID
32452474
Source
epmc
Published In
Biomaterials Science
Published Date
DOI
10.1039/d0bm00521e

The effects of CCL3 on dendritic cell migration and immune cell activation.

Authors
Schaller, TH; Batich, KA; Hotchkiss, K; Cui, X; Sanchez-Perez, L; Sampson, JH
MLA Citation
Schaller, Teilo H., et al. “The effects of CCL3 on dendritic cell migration and immune cell activation.Cancer Immunology Research, vol. 8, no. 4, AMER ASSOC CANCER RESEARCH, 2020, pp. 74–75.
URI
https://scholars.duke.edu/individual/pub1438495
Source
wos
Published In
Cancer Immunology Research
Volume
8
Published Date
Start Page
74
End Page
75

First in human dose calculation of a single-chain bispecific antibody targeting glioma using the MABEL approach.

BACKGROUND: First-in-human (FIH) clinical trials require careful selection of a safe yet biologically relevant starting dose. Typically, such starting doses are selected based on toxicity studies in a pharmacologically relevant animal model. However, with the advent of target-specific and highly active immunotherapeutics, both the Food and Drug Administration and the European Medicines Agency have provided guidance that recommend determining a safe starting dose based on a minimum anticipated biological effect level (MABEL) approach. METHODS: We recently developed a T cell activating bispecific antibody that effectively treats orthotopic patient-derived malignant glioma and syngeneic glioblastoma in mice (hEGFRvIII:CD3 bi-scFv). hEGFRvIII:CD3 bi-scFv is comprized of two single chain antibody fragments (bi-scFvs) that bind mutant epidermal growth factor receptor variant III (EGFRvIII), a mutation frequently seen in malignant glioma, and human CD3ε on T cells, respectively. In order to establish a FIH dose, we used a MABEL approach to select a safe starting dose for hEGFRvIII:CD3 bi-scFv, based on a combination of in vitro data, in vivo animal studies, and theoretical human receptor occupancy modeling. RESULTS: Using the most conservative approach to the MABEL assessment, a dose of 57.4 ng hEGFRvIII:CD3 bi-scFv/kg body weight was selected as a safe starting dose for a FIH clinical study. CONCLUSIONS: The comparison of our MABEL-based starting dose to our in vivo efficacious dose and the theoretical human receptor occupancy strongly supports that our human starting dose of 57.4 ng hEGFRvIII:CD3 bi-scFv/patient kg will be safe.
Authors
MLA Citation
Schaller, Teilo H., et al. “First in human dose calculation of a single-chain bispecific antibody targeting glioma using the MABEL approach.J Immunother Cancer, vol. 8, no. 1, Apr. 2020. Pubmed, doi:10.1136/jitc-2019-000213.
URI
https://scholars.duke.edu/individual/pub1437252
PMID
32273346
Source
pubmed
Published In
Journal for Immunotherapy of Cancer
Volume
8
Published Date
DOI
10.1136/jitc-2019-000213

FIRST-IN-HUMAN DOSING CONSIDERATIONS OF A BISPECIFIC ANTIBODY FOR TREATING GLIOBLASTOMA

Authors
MLA Citation
Schaller, Teilo, et al. “FIRST-IN-HUMAN DOSING CONSIDERATIONS OF A BISPECIFIC ANTIBODY FOR TREATING GLIOBLASTOMA.” Neuro Oncology, vol. 21, OXFORD UNIV PRESS INC, 2019, pp. 84–84.
URI
https://scholars.duke.edu/individual/pub1432893
Source
wos
Published In
Neuro Oncology
Volume
21
Published Date
Start Page
84
End Page
84

4-1BB Agonism Averts TIL Exhaustion and Licenses PD-1 Blockade in Glioblastoma and Other Intracranial Cancers.

PURPOSE: The success of checkpoint blockade against glioblastoma (GBM) has been disappointing. Anti-PD-1 strategies may be hampered by severe T-cell exhaustion. We sought to develop a strategy that might license new efficacy for checkpoint blockade in GBM. EXPERIMENTAL DESIGN: We characterized 4-1BB expression in tumor-infiltrating lymphocytes (TIL) from human GBM. We implanted murine tumor models including glioma (CT2A), melanoma (B16), breast (E0771), and lung carcinomas intracranially and subcutaneously, characterized 4-1BB expression, and tested checkpoint blockade strategies in vivo. RESULTS: Our data reveal that 4-1BB is frequently present on nonexhausted CD8+ TILs in human and murine GBM. In murine gliomas, 4-1BB agonism and PD-1 blockade demonstrate a synergistic survival benefit in a CD8+ T-cell-dependent manner. The combination decreases TIL exhaustion and improves TIL functionality. This strategy proves most successful against intracranial CT2A gliomas. Efficacy in all instances correlates with the levels of 4-1BB expression on CD8+ TILs, rather than with histology or with intracranial versus subcutaneous tumor location. Proffering 4-1BB expression to T cells licenses combination 4-1BB agonism and PD-1 blockade in models where TIL 4-1BB levels had previously been low and the treatment ineffective. CONCLUSIONS: Although poor T-cell activation and severe T-cell exhaustion appear to be limiting factors for checkpoint blockade in GBM, 4-1BB agonism obviates these limitations and produces long-term survival when combined with anti-PD-1 therapy. Furthermore, this combination therapy is limited by TIL 4-1BB expression, but not by the intracranial compartment, and therefore may be particularly well-suited to GBM.
Authors
Woroniecka, KI; Rhodin, KE; Dechant, C; Cui, X; Chongsathidkiet, P; Wilkinson, D; Waibl-Polania, J; Sanchez-Perez, L; Fecci, PE
MLA Citation
Woroniecka, Karolina I., et al. “4-1BB Agonism Averts TIL Exhaustion and Licenses PD-1 Blockade in Glioblastoma and Other Intracranial Cancers.Clin Cancer Res, vol. 26, no. 6, Mar. 2020, pp. 1349–58. Pubmed, doi:10.1158/1078-0432.CCR-19-1068.
URI
https://scholars.duke.edu/individual/pub1425254
PMID
31871298
Source
pubmed
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Volume
26
Published Date
Start Page
1349
End Page
1358
DOI
10.1158/1078-0432.CCR-19-1068

Research Areas:

Animals
Animals, Genetically Modified
Antibody Specificity
Antigen-Antibody Complex
Antigens
Antigens, Neoplasm
Autoantigens
Autoimmunity
Azacitidine
Brain
Cancer Vaccines
Cancer--Immunotherapy
Cell Death
Cell Line
Cell Membrane
Cell Movement
Cell Survival
Chemokines
Combined Modality Therapy
Cytokines
DNA Methylation
Disease Models, Animal
Drug Evaluation, Preclinical
Epitopes
Gene Expression
Gene Expression Regulation
Gene Targeting
Gene Transfer Techniques
Gene therapy
Genetic Engineering
Genetic Therapy
Genetic Vectors
Glioblastoma
Immunity, Innate
Immunization
Immunotherapy, Adoptive
Inflammation
Inflammation Mediators
Lymphocyte Activation
Lymphopenia
Melanocytes
Melanoma, Experimental
Models, Molecular
Neoplasm Invasiveness
Neoplasm Metastasis
Neoplasm Transplantation
Neoplasms, Experimental
Oncolytic Virotherapy
Organ Specificity
Phagocytosis
Recombinant Proteins
Sensitivity and Specificity
Signal Transduction
Skin Neoplasms
Substrate Specificity
Surface Plasmon Resonance
T cells
Treatment Outcome
Tumor Escape
Whole-Body Irradiation
Xenograft Model Antitumor Assays