Weizmann Institute Unveils ‘Smart’ Immunotherapy to Overcome Cancer Drug Resistance

Scientists at the Weizmann Institute of Science have developed a novel immunotherapy approach designed to dismantle the defense mechanisms of tumors, offering new hope for patients who have developed resistance to existing cancer treatments.

The study, published recently in the journal Cell, details the creation of a new class of biological molecules called MiTEs (Myeloid‑targeted immunocytokines and natural killer/T‑cell Enhancers). This treatment targets a specific type of immune cell—macrophages expressing the TREM2 receptor—which tumors often “hijack” to suppress the body’s immune response and promote cancer growth.

“As tumors hijack macrophages to suppress immune responses and promote growth, our goal has been to re‑educate these cells rather than remove them,” Prof. Ido Amit, director of Weizmann’s Immunotherapy Research Center told Ynet.

The research team, led by Michelle von Locquenghien, Pascale Zwicky, and Ken Xie, utilized spatial transcriptomics to map gene activity within human tumors. They discovered that these immune-suppressing macrophages were frequently located in close proximity to “exhausted” killer T-cells—the immune cells responsible for destroying cancer but which had lost their ability to function.

To counter this, the newly engineered MiTEs perform a dual function: they block the suppressive macrophages and simultaneously deliver an immune-boosting cytokine known as IL-2 to re-energize the exhausted killer cells.
A critical innovation in the design of MiTEs is a safety mechanism likened to a “molecular mask.” The IL-2 component remains inactive while circulating through the bloodstream to prevent toxic, widespread immune reactions. The mask is removed only when it encounters specific enzymes found exclusively within the tumor environment.

“The dual function of MiTEs enables them to attack the tumor from multiple immune angles at once,” said von Locquenghien.

In preclinical trials using mice, the treatment caused tumors to shrink and successfully remodeled the immune environment. Further testing on human renal-cell carcinoma tissue demonstrated robust immune activation. The researchers believe this approach could have broad applicability across various cancer types and may work synergistically with chemotherapy and radiation.

“With MiTEs, we may have found a way to convert the tumor’s shield into the very weapon that defeats it,” Prof. Amit concluded.

Cancer treatments often fail because tumors are excellent at tricking the human body into protecting them. Here is a breakdown of how this new treatment works using a simple analogy.

Normally, the body has cells called macrophages (the “cleanup crew”) that eat up debris and bad cells.

In cancer, the tumor tricks these macrophages into working for the enemy. These specific “traitor” macrophages (identified by a tag called TREM2) surround the tumor and act as bodyguards. They put the actual soldiers (Killer T-cells) to sleep, preventing them from attacking the cancer.