Joanne Shea
A5004021040- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Biosimilars and Bioanalytical Methods
- Monoclonal and Polyclonal Antibodies Research
- Advancements in Semiconductor Devices and Circuit Design
- Cancer Immunotherapy and Biomarkers
- Viral Infectious Diseases and Gene Expression in Insects
- Semiconductor materials and devices
- CRISPR and Genetic Engineering
- Nanowire Synthesis and Applications
- Cytomegalovirus and herpesvirus research
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- Chronic Lymphocytic Leukemia Research
- Lymphoma Diagnosis and Treatment
University of Pennsylvania
2014-2025
CRISPR-Cas9 gene editing provides a powerful tool to enhance the natural ability of human T cells fight cancer. We report first-in-human phase 1 clinical trial test safety and feasibility multiplex engineer in three patients with refractory Two genes encoding endogenous cell receptor (TCR) chains, TCRα (
Purpose: Treatments are limited for metastatic melanoma and triple-negative breast cancer (mTNBC). This pilot phase I trial (NCT03060356) examined the safety feasibility of intravenous RNA-electroporated chimeric antigen receptor (CAR) T cells targeting cell-surface cMET. Experimental Design: Metastatic or mTNBC subjects had at least 30% tumor expression cMET, measurable disease progression on prior therapy. Patients received up to six infusions (1 × 10e8 cells/dose) CAR without...
Chimeric antigen receptor (CAR) T cells targeting CD19 have transformed the treatment of B-cell cancers, but many patients do not long-term remission. We designed an anti-CD19 enhanced (armored) CAR T-cell product (huCART19-IL18) that secretes interleukin-18 to enhance antitumor activity. In this study, we assessed safety, feasibility, and preliminary efficacy huCART19-IL18 in with relapsed or refractory lymphoma after previous therapy. Using a 3-day manufacturing process, administered...
7004 Background: A substantial proportion of patients (pts) with relapsed/refractory (R/R) non-Hodgkin lymphomas (NHL) will not derive a long-term benefit from the existing anti-CD19 chimeric antigen receptor (CAR) T cells. To enhance therapeutic efficacy, we have engineered huCART19-IL18, 4 th generation 4-1BB construct, armored ability to secrete pro-inflammatory cytokine, IL-18. Methods: This is first-in-human trial using huCART19-IL18 for CD19+ B-cell malignancies (NCT04684563)....
10035 Background: Advanced relapsed/refractory melanoma and metastatic triple-negative breast cancer are lethal diseases for which effective therapies limited. We conducted a pilot phase I clinical trial (NCT03060356) to establish the safety feasibility of intravenous autologous chimeric antigen receptor (CAR) T cell immunotherapy targeting cMET, cell-surface that is highly expressed in these cancers. Methods: Subjects had or unresectable (Mel) (BC) with ≥30% expression cMET on archival...
<h3>Background</h3> Most women with epithelial ovarian cancer develop uniformly incurable disease recurrence. Chimeric antigen receptor (CAR) T cells pair the MHC-independent tumor-recognition capabilities of monoclonal antibodies cytotoxicity effector cells. The success CAR cell therapy in solid tumors has been hindered by (1) difficulty identifying highly expressed, tumor-specific, surface target antigens; (2) limited trafficking and infiltration; (3) suboptimal cytotoxic activity. Alpha...
<p>Supplementary Figure 2: Representative immunohistochemical staining for Subject 27 with metastatic triple-negative breast cancer; lymph node biopsy. Panel A shows CD8 prior to infusion and B at the time of post-infusion biopsy.</p>
<p>Supplementary Figure 1. : Representative immunohistochemical staining for Subject 74 with metastatic melanoma; lymph node biopsy. Panel A: pS6 prior to infusion; B: at post-infusion biopsy; C: Ki-67 D: biopsy.</p>
<div>Abstract<p>Purpose: Treatments are limited for metastatic melanoma (MM) and triple-negative breast cancer (mTNBC). This pilot phase I trial (NCT03060356) examined the safety feasibility of intravenous RNA- electroporated chimeric antigen receptor (CAR) T cells targeting cell-surface cMET. Patients Methods: MM or mTNBC subjects had at least 30% tumor expression cMET, measurable disease progression on prior therapy. received up to 6 infusions (1x10e8 / dose) CAR without...
<p>Supplementary Figure 1. : Representative immunohistochemical staining for Subject 74 with metastatic melanoma; lymph node biopsy. Panel A: pS6 prior to infusion; B: at post-infusion biopsy; C: Ki-67 D: biopsy.</p>
<p>Supplementary Figure 2: Representative immunohistochemical staining for Subject 27 with metastatic triple-negative breast cancer; lymph node biopsy. Panel A shows CD8 prior to infusion and B at the time of post-infusion biopsy.</p>
<p>Response</p>
<p>Study procedures. Participant study procedures including cell collection/manufacturing timeline as well infusion schedule from eligibility confirmation onward.</p>
<p>Patient population</p>
<p>mRNA signals corresponding to CAR T cells in peripheral blood</p>
<p>Supplementary Figure 2: Representative immunohistochemical staining for Subject 27 with metastatic triple-negative breast cancer; lymph node biopsy. Panel A shows CD8 prior to infusion and B at the time of post-infusion biopsy.</p>
<p>Supplementary Figure 1.: Representative immunohistochemical staining for Subject 74 with metastatic melanoma; lymph node biopsy. Panel A: pS6 prior to infusion; B: at post-infusion biopsy; C: Ki-67 D: biopsy.</p>
<div>Purpose:<p>Treatments are limited for metastatic melanoma and triple-negative breast cancer (mTNBC). This pilot phase I trial (NCT03060356) examined the safety feasibility of intravenous RNA-electroporated chimeric antigen receptor (CAR) T cells targeting cell-surface cMET.</p>Experimental Design:<p>Metastatic or mTNBC subjects had at least 30% tumor expression cMET, measurable disease progression on prior therapy. Patients received up to six infusions (1 × 10e8...
<p>Response</p>
<p>IHC analysis of CD8 in preinfusion and postinfusion tumor tissue. Three subjects had tissue available for analysis; demonstrated an increase cytoxic CD8<sup>+</sup> cells all 3 subjects.</p>
<p>Supplementary Figure 1.: Representative immunohistochemical staining for Subject 74 with metastatic melanoma; lymph node biopsy. Panel A: pS6 prior to infusion; B: at post-infusion biopsy; C: Ki-67 D: biopsy.</p>
<p>IHC analysis of CD8 in preinfusion and postinfusion tumor tissue. Three subjects had tissue available for analysis; demonstrated an increase cytoxic CD8<sup>+</sup> cells all 3 subjects.</p>