Researchers Test Approach to Remove Protective Tumor Barrier, Making Immunotherapies More Effective

Researchers from the United Kingdom may have unlocked the code to removing the barrier protecting tumors from the effects of immunotherapy.

While the results are early, if further research proves the approach effective, it could help boost the impact of treatments like chimeric antigen receptor (CAR) T-cell therapy, which to date hasn’t had much luck in solid tumors.

“This is the first time we’ve been able to effectively target the immune cells that form a barrier around solid tumours,” Francis Mussai, BM, BCh, DPhil, MRCPCH, Cancer Research UK Clinical Scientist Fellow at the University of Birmingham, and lead author of the current study, said in a statement. “If this approach works in patients it could improve treatments for many different types of cancer, in both adults and children.”

Studying the blood of 200 adults and children newly diagnosed with cancer before initiating treatment, the researchers showed that the protein CD33 is present on the surface of immune cells called myeloid-derived suppressor cells (MDSCs), which provide a barricade around tumors, protecting them from the immune system.

By sending out chemical signals that protect tumors from the immune system, MDSCs are able to hinder the ability of T cells to kill tumor cells. When these cells are present in high numbers, a patient’s cancer it more likely to become resistant to treatment, and as a result, to spread to other parts of the body.

Using gemtuzumab ozogamicin—an antibody—drug conjugate used to treat acute myeloid leukemia—that targets CD33, the researchers were able to effectively destroy the MDSCs and restore the ability of the T cells to attack tumor cells.

The researchers were also able to show that active MDSCs prevented CAR-T cells from working in the samples; however, gemtuzumab ozogamicin was able to boost the activity of the CAR-T cells. Based on this finding, Mussai predicted that the approach will have the most impact on CAR T-cell therapy.

While a previous team of researchers was able to break the protective layer around tumors in mice by leveraging antibodies that attach to the MDSC surface, translating the approach into clinical trials proved difficult with the researchers unable to identify a drug target that’s present on human MDSCs.

“Treatments that work with the immune system to kill cancer often fail because it can be difficult for our body’s defences to get access to the tumour cells,” said Mussai. “Our research indicates that giving this antibody drug alongside immunotherapies could dramatically increase the number of patients benefitting from the latest innovations in treatment.”

Reference

Fultang L, Panetti S, Ng M, et al. MDSC targeting with gemtuzumab ozogamicin restores T cell immunity and immunotherapy against cancers [published online August 25, 2019]. EBioMedicine. doi:10.1016/j.ebiom.2019.08.025.