Engineering CAR-neutrophils as a novel therapeutic modality for Aspergillus fumigatus infection
NIAID - National Institute of Allergy and Infectious Diseases
About This Grant
Abstract Invasive fungal infection by Aspergillus species, most commonly by Aspergillus fumigatus, remains one of the leading causes of mortality in immunocompromised patients undergoing solid organ or HSC transplantation because antifungal agents currently used in clinics are poorly effective in treating Aspergillus infection in patients with impaired immunity and neutropenia due to drug toxicities, drug-drug interactions, and the emergence of drug-resistant strains. Neutrophils provide the first line of defense against fungal infection. They effectively kill fungi by fungicidal oxidative bursts, presentation of fungal antigens to T cells, and by increasing fungal clearance by folding their hyphae and decreasing the spreading of infection with extracellular traps (NETs). However, the efficacy of neutrophil transfusions for A. fumigatus has been limited. Therefore, enhancing the antifungal properties of neutrophils is essential for advancing adoptive neutrophil transfer for treating Aspergillus infections. In this application, we aim to develop a novel therapeutic approach to effectively target A. fumigatus infections using induced pluripotent stem cell (iPSC)-derived neutrophils (iNeutrophils) armed with anti-Aspergillus CARs. The major goal of the R21 phase is to provide proof of principle that iNeutrophils equipped with anti-Aspergillus CARs possess superior fungicidal properties. In Aim 1, we will identify the single-chain variable fragment (scFv) that is most effective in iPSC-derived neutrophils for targeting A. fumigatus. In Aim 2, we will characterize the anti-fungal potential of anti-A. fumigatus CAR-iNeutrophils in vitro. If the R21 milestones are achieved, we will advance the development of CAR-iNeutrophil therapies into the R33 phase by enhancing their antifungal potential and demonstrating their efficacy and safety in vivo. In Aim 3, we will identify the most effective CAR configuration and genetic modifications that enhance the fungicidal properties of iNeutrophils. In Aim 4, we will assess the efficacy and toxicity of CAR-iNeutrophils in vivo using zebrafish larvae and invasive pulmonary Aspergillosis mouse models. Overall, generating CAR-iNeutrophils that directly target fungal species will enable the development of a new class of antifungal therapies. These therapies will employ the adoptive transfer of readily available neutrophils with enhanced antifungal functions to treat life-threatening drug-resistant A. fumigatus infections in patients with neutropenia or dysfunctional neutrophils.
Grant Summary
Engineering CAR-neutrophils as a novel therapeutic modality for Aspergillus fumigatus infection is a NIAID - National Institute of Allergy and Infectious Diseases grant providing up to $214K for university, nonprofit, healthcare org. Applications are due 2028-04-30 (open). Check eligibility and apply with FindGrants.
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Up to $214K
2028-04-30
- 1Confirm your organization is eligible for Engineering CAR-neutrophils as a novel therapeutic modality for Aspergillus fumigatus infection from NIAID - National Institute of Allergy and Infectious Diseases, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIAID - National Institute of Allergy and Infectious Diseases before the deadline.
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Engineering CAR-neutrophils as a novel therapeutic modality for Aspergillus fumigatus infection: Frequently Asked Questions
Who is eligible for the Engineering CAR-neutrophils as a novel therapeutic modality for Aspergillus fumigatus infection?
Engineering CAR-neutrophils as a novel therapeutic modality for Aspergillus fumigatus infection is offered by NIAID - National Institute of Allergy and Infectious Diseases and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Engineering CAR-neutrophils as a novel therapeutic modality for Aspergillus fumigatus infection provide?
Engineering CAR-neutrophils as a novel therapeutic modality for Aspergillus fumigatus infection provides up to $214K per award from NIAID - National Institute of Allergy and Infectious Diseases. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Engineering CAR-neutrophils as a novel therapeutic modality for Aspergillus fumigatus infection deadline?
Applications for Engineering CAR-neutrophils as a novel therapeutic modality for Aspergillus fumigatus infection are due 2028-04-30 (open). Because deadlines can change, verify the date with the funder, NIAID - National Institute of Allergy and Infectious Diseases, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Engineering CAR-neutrophils as a novel therapeutic modality for Aspergillus fumigatus infection?
To apply for Engineering CAR-neutrophils as a novel therapeutic modality for Aspergillus fumigatus infection, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIAID - National Institute of Allergy and Infectious Diseases.