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Published on: November 6, 2020
Cryopreserved Ex Vivo-Expanded Allogeneic Myeloid Progenitor Cell Product Protects Neutropenic Mice From a Lethal
Jos Domen1, Julie L Christensen, Daphne Gille
1Cellerant Therapeutics, San Carlos, CA, USA.
Abstract:
Severe neutropenia induced by chemotherapy or conditioning for hematopoietic cell transplantation often results in morbidity and mortality due to infection by opportunistic pathogens. A system has been developed to generate ex vivo-expanded mouse myeloid progenitor cells (mMPCs) that produce functional neutrophils in vivo upon transplantation in a pathogen challenge model. It has previously been demonstrated that transplantation of large numbers of freshly isolated myeloid progenitors from a single donor provides survival benefit in radiation-induced neutropenic mice. In the present work, an ex vivo-expanded and cryopreserved mMPC product generated from an allogeneic donor pool retains protective activity in vivo in a lethal fungal infection model. Infusion of the allogeneic pooled mMPC product is effective in preventing death from invasive Aspergillus fumigatus in neutropenic animals, and protection is dose dependent. Cell progeny from the mMPC product is detected in the bone marrow, spleen, blood, and liver by flow cytometry 1 week postinfusion but is no longer evident in most animals 4 weeks posttransplant. In this model, the ex vivo-generated pooled allogeneic mMPC product (i) expands and differentiates in vivo; (ii) is functional and prevents death from invasive fungal infection; and (iii) does not permanently engraft or cause allosensitization. These data suggest that an analogous ex vivo-expanded human myeloid progenitor cell product may be an effective off-the-shelf bridging therapy for the infectious complications that develop during hematopoietic recovery following hematopoietic cell transplantation or intensive chemotherapy.
Insights
Ex vivo-expanded myeloid progenitor cells offer protection against fungal infections in neutropenic mice. This "off-the-shelf" therapy shows promise for preventing infections during hematopoietic recovery.
Area of Science:
- Hematology
- Immunology
- Cell Therapy
Background:
- Severe neutropenia, often caused by chemotherapy or hematopoietic cell transplantation conditioning, increases infection risk and mortality.
- Opportunistic infections pose a significant threat to patients with neutropenia.
Purpose of the Study:
- To evaluate the efficacy of ex vivo-expanded, cryopreserved, allogeneic mouse myeloid progenitor cells (mMPCs) in preventing lethal fungal infections in a neutropenic mouse model.
- To determine if this cellular product provides a survival benefit and assess its engraftment and safety profile.
Main Methods:
- Generation of ex vivo-expanded mMPCs from an allogeneic donor pool.
- Transplantation of the mMPC product into neutropenic mice challenged with Aspergillus fumigatus.
- Assessment of survival rates, dose-dependency, cell distribution, and engraftment via flow cytometry.
Main Results:
- Infusion of the allogeneic pooled mMPC product significantly prevented death from invasive Aspergillus fumigatus infection in a dose-dependent manner.
- mMPC progeny were detected in various organs post-transplantation but did not permanently engraft.
- The therapy did not induce allosensitization in the treated animals.
Conclusions:
- Ex vivo-expanded allogeneic mMPCs are functional, prevent lethal fungal infections, and do not permanently engraft or cause allosensitization.
- This approach represents a potential "off-the-shelf" bridging therapy for infectious complications during hematopoietic recovery.
- Further investigation into analogous human myeloid progenitor cell products is warranted for clinical application.
