The biggest bottle neck in Chimeric antigen receptor T-Cell (CAR-T cell) therapy is the 21 days it takes to expand the patient’s T cells before re-infusion into the patient’s blood. For many end-stage cancer patients the 21 day wait-period is a death sentence. We propose to explore a 3-part CAR-T cell therapy with only a 2 day wait time before start of therapy. Secondly, current state-of-the art in CAR-T cell technology is only effective against bloodborne malignancies (e.g. acute lymphoblastic leukemia). CAR-T cell clinical trials against solid malignancies has resulted in poor to fatal results. Reasons for the poor performance has been off-target activation, Tumor lysis syndrome (TLS), Cytokine release syndrome (CRS) and persistent “ON” state of cytotoxic CAR-T cells. Recent literature on the switchable CAR-T cell (sCAR-T-cell) system proposed by two research teams uses a small-molecule switch that has bispecific binding domains directed to the tumor and the sCAR-T cells to redirect the sCAR-T cells to the tumor site. However, at the ideal switch concentration no amelioration of the signs related to both CRS and TLS were observed in comparison to the suicide gene auto-destruct CAR T-cell strategy, with a daily or every other day administration. We propose to explore a non-genetic, quick off switch for the gCAR-T cells in order to reduce off target activation, CRS and TLS.
Aug 30
Nanoparticles that act as an “ON and OFF” switch to improve the safety and effectiveness of CAR-T cancer therapy
Categories:
AD&T Notre Dame, Berthiaume Institute for Precision Health, Combination chemotherapy, Harper Cancer Research Institute, Immunotherapy, metastatic cancer cells
by Prakash
Always thankful for the internal support from Notre Dame Research #notredameresearch for supporting high risk-high gain projects such as mine. Here’s hoping that my faculty research support program initiation grant (FRSP-IG) #FRSP will pave the way for safer, more accessible CAR-T therapies and better quality of life for patients.
Tags: NDNano
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- Request for Information (RFI): NIGMS Mature Synchrotron Program Evaluation May 17, 2024Notice NOT-GM-24-019 from the NIH Guide for Grants and Contracts
- Notice of Participation of the National Institute on Aging in RFA-HG-24-004, "ML/AI Tools to Advance Genomic Translational Research (MAGen) - Development Sites (UG3/UH3 Clinical Trials Not Allowed)" May 17, 2024Notice NOT-AG-24-019 from the NIH Guide for Grants and Contracts
- Notice of NIMHD Participation in RFA-OD-24-012, Predoctoral Training in Advanced Data Analytics for Behavioral and Social Sciences Research (BSSR) - Institutional Research Training Program [T32] May 17, 2024Notice NOT-MD-24-013 from the NIH Guide for Grants and Contracts
- Notice of Changes in NCI K00 Salary Caps in The NCI Predoctoral to Postdoctoral Fellow Transition Award (F99/K00) May 17, 2024Notice NOT-CA-24-054 from the NIH Guide for Grants and Contracts
- Notice of Participation of NIDA in RFA-MH-25-186, "Advancing HIV service delivery through pharmacies and pharmacists (R21 Clinical Trial Optional)" May 16, 2024Notice NOT-DA-24-033 from the NIH Guide for Grants and Contracts
- OPEN House webinar for RFA-NS-24-030: NIH Blueprint and BRAIN Initiative Diversity Specialized Predoctoral to Postdoctoral Advancement in Neuroscience (D-SPAN) Award (F99/K00 Clinical Trial Not Allowed) May 16, 2024Notice NOT-NS-24-101 from the NIH Guide for Grants and Contracts
- Access and Manipulation of Brain Cell Subtypes Implicated in Aging and AD/ADRD (R61/R33 Clinical Trial Not allowed) May 16, 2024Funding Opportunity RFA-AG-25-024 from the NIH Guide for Grants and Contracts. This Notice of Funding Opportunity (NOFO) invites applications proposing innovative strategies to target and manipulate brain cell subtypes that are altered in aging, Alzheimer's Disease (AD), and AD-Related Dementias (ADRDs). ADRDs include frontotemporal disorders (FTD), Lewy body dementia (LBD), vascular contributions to cognitive impairment […]
- NEI Research for Low Vision and Blindness Accessibility Tools (R61/R33 Clinical Trial Optional) May 16, 2024Funding Opportunity RFA-EY-24-003 from the NIH Guide for Grants and Contracts. The purpose of this Notice of Funding Opportunity (NOFO) is to stimulate translational efforts in developing and implementing accessibility devices or interventions that apply new technologies to address challenges faced by individuals living with visual impairment. Critical elements of applications include a clear set […]
- Notice of Intent to Publish a Funding Opportunity Announcement for RNA Modifications Driving Oncogenesis (RNAMoDO; U01 Clinical Trial Not Allowed) May 15, 2024Notice NOT-CA-24-053 from the NIH Guide for Grants and Contracts
- Notice of Change to clarify the correct Component for Submission" used in RFA-DK-25-010 Cystic Fibrosis Research and Translation Centers (P30 Clinical Trial Optional) May 15, 2024Notice NOT-DK-24-021 from the NIH Guide for Grants and Contracts
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