23andMe, Innate Pharma use antibodies to target NK cells for cancer treatment | Biospace

Pictured: Collage of white blood cells and cancer cells/Taylor Tieden biospace

As their name suggests, natural killer (NK) cells essentially recognize and kill stressed cells, such as cancer cells. NK cells are not a new way to treat cancer, but a new class of antibodies gives them an edge in the battle, and drugmakers including 23andMe and Innate Pharma are using this approach to develop cell therapies for a range of cancers.

Lewis Lanier, professor of microbiology and immunology at the University of California, San Francisco, said NK cells have many receptors that recognize specific stress ligands present on cancer cells. biospace. Antibody-based therapies promote the anti-tumor activity of NK cells by manipulating receptor-ligand interactions and help NK cells infiltrate tumor sites.

Although their approaches are different, 23andMe and Innate are both developing such therapies to activate the intrinsic ability of NK cells to recognize and kill tumor cells.

Discover new IO targets

Founded in April 2006, 23andMe is one of the best-known direct-to-consumer genetic testing companies.

Jennifer Low, director of therapy development at 23andMe, tells us biospace 80% of customers agree to provide their health data, including health experiences, family history, activity and medical records.

Low said the company’s genetic repository contains genotype and phenotype data from 15 million people, including information on genetic variation that informs its internal drug discovery programs as well as those initiated through collaborations. Specifically, she noted, the repository contains information about portions of the genome that could provide insights into the development of novel immuno-oncology therapies.

The real problem in developing cancer therapies, Lanier said, is that you need a target that is not expressed on healthy tissue. If one could look through these large data sets and find evidence that certain tumor ligands are overexpressed, this could be exploited therapeutically.

Earlier this month, 23andMe presented data from two of its clinical-stage programs at the American Association for Cancer Research annual meeting. One of the antibodies, 23ME-01473, targets soluble ULBP6, a major immunosuppressant released by tumor cells. The new target discovered using the company’s genetic and health investigation library is a ligand for NKG2D, an NK cell surface receptor that recognizes multiple stress-related ligands expressed on tumor cells. Tumor cells release ULBP6 into the tumor microenvironment to bind NKG2D, thereby bypassing NK cell recognition. According to 23andMe, blocking ULBP6-NKG2D binding may restore immune cell recognition and killing of cancer.

There is some data showing that ULBP6 is overexpressed in certain tumors, Lanier said, adding that using antibodies against ULBP6 is a good strategy. Low said that in addition to targeting the ULBP6-NKG2D interaction, 23andMes’ investigational antibodies also have an Fc effector enhancement domain that binds to NK cells and further enhances their function.

23andMe initiated a Phase I clinical trial in March 2024 to evaluate the safety and tolerability of 23ME-01473 in patients with advanced solid tumors who have progressed following standard of care treatment.

NK cell engager

Biopharmaceutical companies have long recognized the potential of NK cells. Recently, NK cell therapy has attracted attention in the field of cell and gene therapy. The global NK cell therapy market size will be US$92 million in 2022 and is expected to reach US$3.1 billion by 2031.

But even without injecting these natural killers into cancer patients, some companies are looking to harness NK cell biology to fight cancer. In addition to 23andMe, other players in the space include Dragonfly Therapeutics, D2M Biotherapeutics and Innate Pharma.

Eric Vivier, President and CEO of Innate, said, “Our therapeutic strategy has two main focuses: releasing NK cells or stimulating NK cells through NK cell engagers. biospace.

Innates’ lead asset, IPH6101/SAR443579, is an antibody-based NK cell engager developed in partnership with Sanofi that targets the NK cell receptors NKp46 and CD16 and the tumor antigen CD123, which is overexpressed in acute myeloid leukemia (AML) . Vivier explains the rationale behind the choice of two NK cell receptors. NKp46 is a stably expressed activating receptor found on NK cells, and CD16 is an antibody receptor that can also stimulate NK cell function.

Innate and Sanofi initiated a Phase II dose expansion trial of IPH6101/SAR443579 last week. The companies plan to enroll 126 patients with cancers including AML, B-cell acute lymphoblastic leukemia and high-risk myelodysplasia.

Vivier said NK cell engagers may have an advantage over T cell engagers because they do not induce the severe immune response of a cytokine storm, leading to excessive release of pro-inflammatory cytokines, organ damage and mortality, which is commonly seen with the latter.

Another drug candidate, IPH6501, is an NK cell engager that also targets NKp46 and CD16, as well as the tumor antigen CD20, and is equipped with a variant of interleukin 2 (IL-2). Vivier explained that adding cytokines such as IL-2 to the NK cell engager induces cell proliferation pathways and enhances immune responses.

Lanier agreed. He points out that while NK cell engagers draw NK cells from the blood into the tumor, the NK cells that enter the tumor are shut down by the immunosuppressive microenvironment. Introduction of cytokines awakens NK cells and restores their function.

Vivier said that in preclinical studies, IPH6501 showed massive infiltration of NK cells into tumors and good control of tumor growth. The asset’s safety and tolerability are currently being evaluated in a Phase I clinical trial in patients with relapsed/refractory non-Hodgkin’s lymphoma, with preliminary data expected in 2025.

Articles published in J in 2023Journal of Hematology and Oncology It is believed that T-cell engagers may revolutionize the treatment of hematological malignancies in the short term because they are more effective than traditional monoclonal antibodies that recognize the same tumor antigens. The authors note that bispecific NK cell engagers have similar efficacy but less severe side effects, while trispecific antibodies further increase competition.

Taken together, these engineered molecules may change the treatment paradigm for relapsed or refractory hematologic malignancies, the authors wrote.

Sunitha Chari is a freelance science writer and academic editor based in Toronto. Check out more of her work at sunithachari.contently.com and contact her at sunithachari.02@gmail.com.