Solid Tumor Immunotherapies Using Off-The-Shelf Monocytes
Engineered monocytes to target cancerous cells, secrete immune-boosting cytokines, and coordinate anti-tumor immune responses against solid tumors
Technology Overview
Dr. Colleen S. Delaney
Solid tumors are difficult to treat with cellular immunotherapies. Even if therapeutic cells get into the tumor interior, they often encounter an immunosuppressive microenvironment that can shut off their tumor-fighting capabilities. Stem cell transplantation physician Colleen Delaney, MD, MSc, has a solution: Engineered monocytes that naturally migrate into tumors to become resident immune cells whose functions include driving antitumor immune responses and eliminating cancer cells.
Monocytes do not expand ex vivo, however, which has limited their therapeutic applications. Dr. Delaney overcame this challenge by using pooled donor cord blood as the source for generating monocytes. Her lab developed a low-cost, standardized, highly scalable system that produces clinically meaningful numbers of monocytes. The Delaney Lab uses a proprietary protocol to expand CD34 hematopoietic stem cells and then differentiate them into monocytes that, when introduced therapeutically, circulate in the blood before entering tumors to terminally differentiate into long-lived macrophages.
The monocytes are generated from healthy donor cord blood cells, so they have little or no exposure to infectious agents or external toxins, including from treatment-associated chemotherapy or radiation. Thus, the protocol results in high-quality monocytes, reducing the risk of manufacturing failure often associated with generating autologous (patient-derived) cell therapies.
Clinical uses of ready-to-use monocytes
The Delaney Lab demonstrated that the monocytes retain viability and function following cryopreservation and thaw, meaning that hundreds of vials of ready-to-use cells can be banked for use as an allogeneic cell therapy with no need for HLA matching before use. The cells expand the accessibility and options for cell therapy by providing a readily available, “off-the-shelf” treatment without the long vein-to-vein wait times of autologous cell therapies.
During the cell expansion process, the cells can be custom engineered to target specific tumors through the expression of a chimeric antigen receptor (CAR) or other binding proteins. The cells can also be programmed to secrete armoring cytokines to counteract the immunosuppressive tumor microenvironment and recruit and activate other cancer-fighting immune cells. The Delaney Lab is collaborating on methods to directly infuse or insert engineered monocytes into tumors, including during tumor-removing surgery. This strategy could overcome the challenges of delivering therapeutic cells to brain cancers.
Dr. Delaney is a founder and leader of two cell therapy companies to date, Deverra Therapeutics and Nohla Therapeutics, raising more than $175 million in funding for them. She is interested in industry partnerships to advance engineered allogeneic monocytes into clinical practice. She is particularly interested in developing treatments for brain tumors, neuroblastomas and other solid tumors. The Delaney Lab can rapidly generate and test monocytes that target cells or secrete proteins that are of interest to an industry partner.
Stage of Development
- Preclinical in vitro
- Preclinical ex vivo
- Preclinical in vivo
Partnering Opportunities
- Collaborative research and development
- Sponsored research agreement
- Consultation agreement
- Custom CAR-myeloid cell generation
- Licensing agreement
- Clinical trials
- Investor-initiated clinical trials
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Publications
- Hsieh E, Jamison B, Brempelis K, Delaney C, et al. Abstract 32: Engineering cord blood CD34+ cells for the generation of allogeneic NK or myeloid cell immunotherapies. Stem Cells Transl Med. 2024;13(Suppl 1):S36.
- Brempelis K, Pudiwitr J, Stoltzman C … Delaney C. Generation of monocytes and macrophages from CD34+ cord blood cells for cell therapy. Cytotherapy. 2024;26(Suppl 6):S190.
- Kreuser S, Davis N, Stoltzman C, Delaney C. Abstract 3: Generation of myeloid cells from cord blood-derived CD34+ cells for therapeutic intent. Stem Cells Transl Med. 2022;11(Suppl 1):S5.
- Shi PA, Luchsinger LL, Greally JM, Delaney CS. Umbilical cord blood: an undervalued and underutilized resource in allogeneic hematopoietic stem cell transplant and novel cell therapy applications. Curr Opin Hematol. 2022;29(6):317-326.
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Last updated June 2026