Heating up tumours could make CAR T therapy more effective, study finds

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A preclinical study led by scientists at the UCLA Jonsson Comprehensive Cancer suggests that heating solid tumours during CAR T-cell therapy can enhance the treatment’s success.

The researchers found that when a heating technique called photothermal ablation was combined with the infusion of CAR T cells, it suppressed melanoma tumour growth for up to 20 days in mice. Among the mice that were treated with the combination, 33 percent were still tumour free after the 20-day mark.

T cells that have been genetically engineered with chimeric antigen receptor, or CAR, have successfully been used to treat many patients with lymphoma and leukemia. But CAR T cell therapy has been less successful for treating solid tumours because the tumours have a protective microenvironment, which makes it harder for the CAR T cells to break into the tumour and keep the T cells activated.

The UCLA scientists decided to test whether combining CAR T therapy with photothermal therapy could overcome that obstacle. Photothermal therapy is a minimally invasive technique that uses heat from laser energy to kill cancer cells; it is already being used to treat a variety of cancers and other medical conditions. The researchers tested a mild hyperthermia about 40 degrees Celsius (about 104 degrees Fahrenheit) to see if it could help enhance the CAR T cells to better attack the tumour.

The UCLA-led team tested the technique in mice that were injected with human melanoma tumours. A photothermal agent was injected into the tumours and then irradiated with the laser to heat them. Then, CAR T cells were injected intravenously. Raising the temperature of the laser to about 40 degrees Celsius helped expand blood vessels associated with the tumour, enhancing T cell growth.

By enhancing the power of CAR T cell therapy, the technique could eventually improve the prognosis for people with hard-to-treat solid tumours. The researchers will continue testing the strategy in animals to optimize the heating duration and temperature before determining whether it can be tested on humans.

Zhen Gu, a professor of bioengineering at the UCLA Samueli School of Engineering, member of the Jonsson Cancer Center and member of the California NanoSystems Institute at UCLA, is the study’s co-senior author. The paper’s other senior author is Dr. Gianpietro Dotti of the University of North Carolina, Chapel Hill. The first author is Qian Chen, a postdoctoral researcher in Gu’s laboratory.

The research is published in the journal Advanced Materials.


Paper: Photothermal Therapy Promotes Tumour Infiltration and Antitumour Activity of CAR T Cells, Advanced Materials (2019). DOI: 10.1002/adma.201900192 , https://onlinelibrary.wiley.com/doi/full/10.1002/adma.201900192

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