In CAR-T therapies, patient T cells are genetically modified to recognize and destroy cancer cells. A new approach developed by Peter MacCallum Cancer Centre aims to overcome barriers that have limited these treatments' success against solid tumors.
Engineered cells deliver medication precisely at tumor contact
Solid tumors create physical barriers against immune cells, suppress T-cell function locally, and raise the risk of severe side effects when immunostimulatory molecules circulate throughout the body. The Precision Guided Munition CAR-T platform uses CRISPR gene editing so that T cells release their medication only when contacting tumor cells, activating body cytokine genes only after binding to target molecules.
Multiple myeloma first, then potentially solid tumors
The Frontier Health and Medical Research Grant supports a program led by Beavis and Jane Oliaro to validate the platform first in multiple myeloma before expanding to solid tumors such as breast and lung cancer. Cell Therapies Pty Ltd will manufacture the product, and Simon Harrison will lead the first clinical trial. More than 2,700 Australians receive a multiple myeloma diagnosis annually. Five-year survival rates stand at approximately 61 percent.
Mouse trials show promise, but questions remain
In multiple mouse models, the engineered cells produced stronger anti-tumor responses than conventional CAR-T cells while avoiding high circulating cytokine levels linked to toxicity. Laboratory tests in mice showed near 100 percent cure rates for solid tumors in models for breast, colon, and ovarian cancer. The medical team noted that animal model successes do not automatically translate to humans. Earlier studies with differently designed cytokine systems ended prematurely due to severe toxicity. The planned trial in multiple myeloma patients serves as a step toward potential expansion to solid tumors.