The goal is for researchers to better understand how leukemia cells escape the immune system’s notice and thus fail to trigger an immune response.
The collaboration is supporting the development of NexImmune’s Artificial Immune Modulation (AIM) nanoparticle technology for treating AML, according to a press release. This technology uses tumor-specific antigens to train a patient’s own immune T-cells to recognize the antigens on cancer cells and launch an immune response. Tumor-specific antigens are proteins found on the outside of pathogens — organisms that cause disease — that trigger immune reactions.
City of Hope is currently one site of a Phase 1/2 clinical trial (NCT04284228) assessing the safety, tolerability, and antitumor activity of NEXI-001, NexImmune’s T-cell therapy candidate, among AML patients with relapsed disease after a donor stem cell transplant. The trial is still enrolling and seeks to recruit approximately 22 participants across six U.S. sites.
NEXI-001 is an adoptive cellular therapy product that contains nanoparticle-trained CD8+ T cells, which are a type of immune cells specific for certain antigens. These cells are grown to greater numbers in the lab from donor-derived stem cells. CD8+ refers to the presence of the CD8 receptor on these cells, which is used, among other things, in tumor surveillance.
Data from the first five patients dosed in the trial, and representing a median of four months of follow-up, have shown that there have been no cases of acute Graft versus Host Disease (aGvHD) — a serious complication commonly associated with bone marrow and stem cell transplants — or other serious adverse events related to the treatment.
In three patients, the levels of white blood cells (leukocytes) returned to normal within three to 35 days. Additionally, a single infusion of NEXI-001 T cells triggered a broad, rapid, and robust immune response, with the expansion and migration of individual NEXI-001 T cells from the blood to the bone marrow of each patient.
City of Hope, at several locations in California, houses one of the world’s largest collections of primary leukemia samples. These are the first cancerous cells to occur in a patient, before knock-on mutations and metastases occur.
The center will use these samples, and those gathered from participants in the NEX-001 trial, to identify which mechanisms leukemic cells use to evade the immune system. Researchers also hope these samples will help them identify new antigen targets found on leukemic “blast” cells — immature cells that can give rise to other white blood cells — stem cells, and any cells that enable those two cell types to survive.
NexImmune will include these newly identified target antigens on their AIM nanoparticles and will evaluate their anti-tumor potency, tumor-specific killing ability, and the length of those responses in pre-clinical leukemia models.
By loading multiple antigens onto each nanoparticle, NexImmune hopes to expand the T-cells’ ability to recognize and target a range of harmful cancer cells.
“Research between NexImmune and City of Hope will inform a scientific understanding of how the immune system can address certain tumor escape mechanisms to more effectively fight aggressive cancers like AML, and how this might be accomplished with NexImmune’s AIM technology and T cell products,” said Monzr Al Malki, MD, director of City of Hope’s unrelated donor BMT program.
“Based on our current clinical experience with this technology, we’re excited to learn what more this research will tell us,” Al Malki said.
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