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
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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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- Notice of Clarification of NIMH Specific Areas of Research Interest in PAR-24-144 and PAR-24-145, "Support for Research Excellence (SuRE) and (SuRE-First) Awards (R16 - Clinical Trial Not Allowed) April 23, 2024Notice NOT-MH-24-250 from the NIH Guide for Grants and Contracts
- NIDA MERIT Awards for Early Stage Investigators (ESI) April 23, 2024Notice NOT-DA-24-017 from the NIH Guide for Grants and Contracts
- Phase-out and Termination of NIDA MERIT Awards for Established Investigators April 23, 2024Notice NOT-DA-24-016 from the NIH Guide for Grants and Contracts
- Ruth L. Kirschstein National Research Service Award (NRSA) Stipends, Tuition/Fees and Other Budgetary Levels Effective for Fiscal Year 2024 April 23, 2024Notice NOT-OD-24-104 from the NIH Guide for Grants and Contracts
- Mentored Quantitative Research Development Award (Parent K25 Independent Clinical Trial Not Allowed) April 23, 2024Funding Opportunity PA-24-191 from the NIH Guide for Grants and Contracts. The purpose of the Mentored Quantitative Research Career Development Award (K25) is to attract to NIH-relevant research those investigators whose quantitative science and engineering research has thus far not been focused primarily on questions of health and disease. The K25 award will provide support […]
- Mentored Quantitative Research Development Award (Parent K25 Independent Basic Experimental Studies with Humans Required) April 23, 2024Funding Opportunity PA-24-192 from the NIH Guide for Grants and Contracts. The purpose of the Mentored Quantitative Research Career Development Award (K25) is to attract to NIH-relevant research those investigators whose quantitative science and engineering research has thus far not been focused primarily on questions of health and disease. The K25 award will provide support […]
- Mentored Quantitative Research Development Award (Parent K25 Independent Clinical Trial Required) April 23, 2024Funding Opportunity PA-24-190 from the NIH Guide for Grants and Contracts. The purpose of the Mentored Quantitative Research Career Development Award (K25) is to attract to NIH-relevant research those investigators whose quantitative science and engineering research has thus far not been focused primarily on questions of health and disease. The K25 award will provide support […]
- Human Leukocyte Antigen (HLA) and Killer-cell Immunoglobulin-like Receptor (KIR) Region Genomics in Immune-Mediated Diseases (U01 Clinical Trial Not Allowed) April 23, 2024Funding Opportunity RFA-AI-24-017 from the NIH Guide for Grants and Contracts. The purpose of this notice of funding opportunity (NOFO) is to support research that 1) defines associations between variations in human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptor (KIR) genetic regions and immune-mediated diseases, 2) elucidates mechanisms underlying these associations with the goal […]
- Cystic Fibrosis Research and Translation Centers (P30 Clinical Trial Optional) April 23, 2024Funding Opportunity RFA-DK-25-010 from the NIH Guide for Grants and Contracts. This Notice of Funding Opportunity (NOFO) invites applications for Cystic Fibrosis (CF) Research and Translation Core Centers. CF Research and Translation Core Centers are designed to support both basic and clinical research on Cystic Fibrosis. CF Research and Translation Core Centers support three primary […]
- Small Business Transition Grant For Early Career Scientists (R41/R42 Clinical Trial Not Allowed) April 23, 2024Funding Opportunity RFA-CA-24-023 from the NIH Guide for Grants and Contracts. Through this Notice of Funding Opportunity (NOFO), the National Cancer Institute (NCI) intends to support early-career academic scientists interested in transitioning to entrepreneurship while also supporting the transfer of technology from academic laboratories into small businesses. Both small businesses and universities are drivers of […]
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