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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- NINDS Policy for applications requesting $500,000 or more in direct costs in any year (excluding consortium F and A)on NIH Parent R01 Notices of Funding Opportunities April 26, 2024Notice NOT-NS-24-079 from the NIH Guide for Grants and Contracts
- NHLBI Outstanding Investigator Award (OIA) (R35 Clinical Trial Optional) April 26, 2024Funding Opportunity RFA-HL-26-002 from the NIH Guide for Grants and Contracts. The purpose of the NHLBI Outstanding Investigator Award (OIA) is to promote scientific productivity and innovation by providing long-term support and increased flexibility to experienced Program Directors/Principal Investigators (PDs/PIs) who are currently PDs/PIs on at least two NHLBI R01-equivalent awards and whose outstanding record […]
- NHLBI Emerging Investigator Award (EIA) (R35 Clinical Trial Optional) April 26, 2024Funding Opportunity RFA-HL-26-003 from the NIH Guide for Grants and Contracts. The purpose of the NHLBI Emerging Investigator Award (EIA) is to promote scientific productivity and innovation by providing long-term support and increased flexibility to experienced Program Directors/Principal Investigators (PDs/PIs) who are currently PDs/PIs on at least two NHLBI R01-equivalent awards and whose outstanding record […]
- Coordinating Center for Type 1 Diabetes TrialNet (U01 Clinical Trial Required) April 26, 2024Funding Opportunity RFA-DK-25-004 from the NIH Guide for Grants and Contracts. The purpose of this Notice of Funding Opportunity (NOFO) is to continue support for the TrialNet Coordinating Center (TNCC). The TrialNet network identifies people with type 1 diabetes (T1D) at stages before and after onset of clinical symptoms and enrolls them in trials and […]
- NIDCD Individual Fellowship Pre-Application Information Session April 26, 2024Notice NOT-DC-24-026 from the NIH Guide for Grants and Contracts
- Notice of Special Interest (NOSI): Administrative Supplement to Support the NCI Cancer Prevention-Interception Targeted Agent Discovery Program (CAP-IT) Research April 26, 2024Notice NOT-CA-24-047 from the NIH Guide for Grants and Contracts
- Small Business Transition Grant for New Entrepreneurs (R43/R44 Clinical Trial Required) April 26, 2024Funding Opportunity PAR-24-132 from the NIH Guide for Grants and Contracts. Through this Notice of Funding Opportunity (NOFO), the National Institutes of Health (NIH) aims to facilitate the career development and transition of investigators new to entrepreneurship with an interest in small business by simultaneously supporting their entrepreneurial development and the conduct of research and […]
- Independent Scientist Award (Parent K02 Independent Basic Experimental Studies with Humans Required) April 26, 2024Funding Opportunity PA-24-180 from the NIH Guide for Grants and Contracts. The purpose of the NIH Independent Scientist Award (K02) is to foster the development of outstanding scientists and enable them to expand their potential to make significant contributions to their field of research. The K02 award provides three to five years of salary support […]
- Independent Scientist Award (Parent K02 - Independent Clinical Trial Required) April 26, 2024Funding Opportunity PA-24-178 from the NIH Guide for Grants and Contracts. The purpose of the NIH Independent Scientist Award (K02) is to foster the development of outstanding scientists and enable them to expand their potential to make significant contributions to their field of research. The K02 award provides three to five years of salary support […]
- Notice of Budget Change in RFA-AI-24-006 Centers for Research in Emerging Infectious Diseases (CREID) Network (U01 Clinical Trial Not Allowed) April 25, 2024Notice NOT-AI-24-046 from the NIH Guide for Grants and Contracts
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