Related Experiment Video
Updated: Feb 2, 2026
09:09
In Silico Clinical Trials for Cardiovascular Disease
Published on: May 27, 2022
2.3K
IND-Enabling Studies for a Clinical Trial to Genetically Program a Persistent Cancer-Targeted Immune System
Cristina Puig-Saus1,2, Giulia Parisi3,2, Angel Garcia-Diaz3,2
1Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine (DGSOM), University of California, Los Angeles (UCLA), Los Angeles, California. aribas@mednet.ucla.edu cpuigsaus@mednet.ucla.edu.
Summary
This study shows that combining genetically modified hematopoietic stem cells (HSCs) and T cells engineered with a specific T-cell receptor (TCR) is safe in preclinical models. This approach aims to improve T-cell persistence and durable clinical responses for cancer therapy.
Area of Science:
- Immunotherapy
- Hematopoietic Stem Cell Transplantation
- Gene Therapy
Background:
- Adoptive cell transfer of T-cell receptor (TCR)-engineered T cells shows promise for durable clinical responses.
- Improving the persistence of these engineered T cells is crucial for sustained therapeutic effects.
Purpose of the Study:
- To conduct preclinical studies for an Investigational New Drug (IND) application.
- To evaluate the safety and efficacy of co-transplanting genetically modified hematopoietic stem cells (HSCs) and T cells engineered with an NY-ESO-1 TCR.
Main Methods:
- HSCs and T cells were genetically modified to express an NY-ESO-1 TCR and a reporter/suicide gene (HSV1-sr39TK) in HSCs.
- Co-administration of modified HSCs and T cells was performed in myelodepleted mice under Good Laboratory Practice (GLP) conditions.
- Safety, persistence, HSC differentiation, transgene immunogenicity, viral insertion, and Good Manufacturing Practice (GMP) cell production were assessed.
Main Results:
- Genetically modified HSCs differentiated into all blood lineages in vivo post-transplantation.
- Coadministration of modified HSCs and T cells did not increase toxicity.
- No detrimental effects on HSC differentiation or evidence of genotoxicity were observed; GMP batches showed adequate stability and functionality.
Conclusions:
- Coadministration of HSCs and T cells engineered with an NY-ESO-1 TCR is safe in preclinical models.
- These findings supported the FDA approval of IND 17471, paving the way for clinical trials.
Related Concept Videos
01:16Clinical Trials
10.5K
Clinical trials are prospective experimental studies conducted on humans to determine the safety and efficacy of treatments, drugs, diet methods, and medical devices. Using statistics in clinical trials enables researchers to derive reasonable and accurate conclusions from the collected data, allowing them to make wise decisions in uncertain situations. In medical research, statistical methods are crucial for preventing errors and bias.
There are four phases in a clinical trial. A phase one...
There are four phases in a clinical trial. A phase one...
10.5K
01:11Clinical Trials: Overview
5.0K
Clinical development focuses on how the drug will interact with the human body and encompasses four key phases of clinical trials, each serving a specific purpose in assessing the safety and effectiveness of new drugs. These phases overlap and build upon one another. Phase I involves a small group of healthy volunteers (typically 20-80 individuals) or, in cases where significant toxicity is expected, patients with the targeted disease, such as cancer or AIDS. The volunteers are tested for...
5.0K
01:12Statistical Software for Data Analysis and Clinical Trials
1.5K
Statistical software is pivotal in data analysis and clinical trials by providing tools to analyze data, draw conclusions, and make predictions. These software packages range from simple data management applications to complex analytical platforms, supporting various statistical tests, models, and simulation techniques. Their significance lies in their ability to handle vast amounts of data with precision and efficiency, enabling researchers to validate hypotheses, identify trends, and make...
1.5K
02:57Targeted Cancer Therapies
8.9K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
8.9K
01:12Trial and Error and Algorithm
420
A problem-solving strategy is a plan of action used to find a solution. Different strategies have distinct action plans. Trial and error involves trying different solutions until one works. For instance, to fix a broken printer, you might check ink levels, ensure the paper tray isn't jammed, and verify the printer's connection to your laptop. This method can be time-consuming but is commonly used. Thomas Edison, for example, used trial and error to find a suitable filament for the light...
420
01:21Aneurysm II: Clinical Manifestations and Diagnostic Studies
349
Thoracic, aortic arch and abdominal aneurysms are significant vascular conditions that can present with various clinical manifestations and lead to serious complications. Understanding these manifestations and the appropriate diagnostic studies is essential for effective management and treatment.Thoracic Aortic AneurysmsThoracic aortic aneurysms often remain asymptomatic until they reach a size that impinges on adjacent structures. They typically cause deep, diffuse chest pain that radiates to...
349