# Bio-engineered Cell Therapy to Treat Candidiasis

> **NIH NIH R21** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2024 · $251,250

## Abstract

PROJECT ABSTRACT
Patients with hematological malignancies, and immunocompromised patients are highly susceptible to Candida
infection. Based on the immune status of the host, the infections may be mild to life- threatening. The goal is to
find novel treatment approaches to give long-term protection against opportunistic Candida spp. without
disturbing normal gut microflora. The rationale underlying this proposal is that the development of CAR-T cell
and CAR-Macrophage based cell therapies will target and recruit host immune system to protect against
opportunistic Candida infection. Recently chimeric antigen receptors (CAR) T-cell based therapy has
revolutionized cancer treatment strategy and showed overall success rate of more than 90% in hematological
malignancies. In pre-clinical studies Aspergillus specific CAR T cells has shown significant reduction in fungal
burden. Thus, the objective of this proposal is to develop CAR constructs to target systemic Candida infections
without disturbing normal gut microflora. We will generate CAR constructs by fusing extracellular domain of the
pattern recognition receptors with cytoplasmic domain of the activation receptors (CA-CAR). The central
hypothesis will
overcome barriers and immune evasion tactics imposed by the Candida spp.
 The central hypothesis will be tested by pursuing two specific aims.:
Aim 1). Generation and functional characterization of T-cells expressing CA-CARs:
Aim 2). Generation and functional characterization of macrophages expressing CA-CARs:
Aims 1 and 2 can be done simultaneously without being dependent on each other. These include (i)
generating CAR constructs by fusing Candida specific targeting domain with cell activating receptors; (ii)
expression of CARs in T cells and macrophages using molecular biology and tissue culture techniques; and
(iii) performing fungicidal assays by monitoring fungal growth real-time using image scanning microscope.
Functional efficacy studies will be done by co-culturing Candida yeast and Candia hyphae. In-vivo efficacy
studies will be done in NSG mice bearing systemic candidiasis. The proposed research is significant, because
it is the first cell-based therapy designed to target Candida that spares the normal commensals. It is also
significant because it will develop a platform that can be extended to study and control other opportunistic
infections. To protect patients from unanticipated CAR T cell/ CAR-Macrophage related toxicity, we will include
a mutant epidermal growth factor receptor (mEGFR) safety switch to induce apoptosis in CAR T cells. This can
be activated by targeting with mEGFR specific antibody. The results of this study will have an important
positive impact especially to overcome barriers such as virulence, antifungal resistance and recruit host
immune system for clearing pathogens. The expected outcomes are that this proposal will lay the groundwork
to develop suitable CARs to control other opportunistic pathogens and provide lon...

## Key facts

- **NIH application ID:** 10809857
- **Project number:** 1R21AI167031-01A1
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Pappanaicken Rangasamy Kumar
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $251,250
- **Award type:** 1
- **Project period:** 2024-08-26 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10809857

## Citation

> US National Institutes of Health, RePORTER application 10809857, Bio-engineered Cell Therapy to Treat Candidiasis (1R21AI167031-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10809857. Licensed CC0.

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