Boosting T cells improves survival in mice with glioblastoma

However, a new study by researchers at Washington University School of Medicine in St.
Louis shows that treatment with an immune-boosting protein called interleukin 7 (IL-7), along with radiation therapy, can increase the number of patients with glioblastoma cells.
survival rate of tumor-bearing mice
.

New mouse studies show that IL-7 increases the number of T cells in tumors and other immune organs

The findings were published Jan.
14 in the American Association for Cancer Research's journal Clinical Cancer Research
.

The study in mice shows ongoing work at the Siteman Cancer Center at Barnes-Jewish Hospital and the Washington University School of Medicine in St.
Louis.
A Phase 1/2 clinical trial investigating a long-acting type of IL-7 in patients with glioblastoma
.

Radiation and chemotherapy are standard treatments for various cancers, including glioblastoma
.

While these therapies are beneficial for cancer, they also damage a patient's T cells, or lymphocytes, which are important for fighting infections

"Previously, a multicenter study by the American Brain Tumor Association showed that patients with low T cell counts lived 6 months shorter than normal patients," said study leader Jian L.
Campian of Washington University School of Medicine and the Siteman Brain Tumor Center.
Dr.
said
.

"We know that glioblastoma patients with low lymphocytes also have low levels of IL-7, a growth factor that supports T cells

The researchers found that mice with glioblastoma, treated with a combination of chemotherapy, radiation, and IL-7, lived longer than mice that received chemotherapy and radiation alone
.

On average, untreated control mice survived about 20 days after tumor implantation

"It's hard to know how these increased survival rates in mice translate to people," said senior author Milan Chheda, associate professor of medicine
.

"If these mice survived at least 3 months with the addition of IL-7, we would expect to see some improvement in patients treated with IL-7

The researchers found that, in addition to increasing the number of T cells in the tumor and tumor environment, IL-7 treatment also increased T cells in the blood and immune organs, including the thymus, spleen and lymph nodes
.

The therapy also reduced T regulatory cells, which are thought to suppress the immune system in the microenvironment of brain tumors

"We were encouraged by the results we saw in mice," said senior author Dinesh Thotala, Ph.
D.
, associate professor of radiation oncology
.

"We also saw evidence that IL-7 could be considered as an alternative to temozolomide, especially in the recent past.

Current immunotherapies, called immune checkpoint inhibitors, work by releasing the brakes on immune cells that are already there, the researchers explained
.

Now that so many glioblastoma patients have depleted their T-cell populations, it's no surprise that immune checkpoint inhibitors have not proven effective

"If we could increase the number of T cells by using IL-7, we wanted to know if adding an immune checkpoint inhibitor would increase the activity of T cells against cancer cells," said Chheda, who treats patients at the Siteman Cancer Center
.

The researchers plan to conduct a follow-up study in glioblastoma patients at Washington University and Mayo Clinic to identify immune checkpoint inhibitors in combination with long-acting IL-7, said Campian, who is now at the Mayo Clinic.
Whether the use can improve the survival rate
.

This work was supported by NeoImmuneTech Inc.
; Oncology Startup Grants, Radiation Oncology Startup Grants; National Institute of Neurological Disorders and Stroke, National Institutes of Health (NIH), Grant Number: R01 NS117149; Alvin J.
Siteman Cancer Research Fund; and the Alvin J.
Siteman Cancer Center Siteman Investment Project, funded by the Barnes-Jewish Hospital Foundation and the Barnard Trust
.

Campian and Chheda report on grants and other support from NeoImmuneTech
.

Journal Reference :

1. Jian L.
   Campian, Subhajit Ghosh, Vaishali Kapoor, Ran Yan, Sukrutha Thotala, Arijita Jash, Tong Hu, Anita Mahadevan, Kasem Rifai, Logan Page, Byung Ha Lee, Sara Ferrando-Martinez, Alexandra A.
   Wolfarth, Se Hwan Yang, Dennis Hallahan, Milan G.
   Chheda, Dinesh Thotala.
   Long-acting recombinant human interleukin-7, NT-I7, increases cytotoxic CD8 T cells and enhances survival in mouse glioma models .
   Clinical Cancer Research , 2022; clincanres.
   0947.
   2021 DOI: 10.
   1158/ 1078-0432.
   CCR-21-0947