Nature sub-journal: Bispecific tumors transform nanoparticles, making the treatment of solid tumors no longer difficult

With the development of medicine, human understanding of cancer and the autoimmune system has deepened, and scientists have realized that the immune system is the sharpest weapon
against tumors and cancer.
Thanks to this, tumor immunotherapy has flourished in recent years, bringing new hope
to the majority of cancer patients.
Unfortunately, although this method is effective for blood types such as leukemia, it has little effect
in treating solid tumors.
Therefore, how to apply tumor immunotherapy to the treatment of solid tumors is an urgent problem
to be solved.
Recently, Jiang Wen of MD Anderson Cancer Center in the United States and others published a research paper
in Nature Nanotechnology entitled: Immunological conversion of solid tumours using a bispecific nanobioconjugate for cancer immunotherapy.

The research developed a nanotechnology platform, bispecific tumor-transforming nanoparticles (BiTNs), that could change the way the immune system responds to solid tumor cells, making solid tumors more sensitive
to immunotherapy.
What's more, the preclinical findings suggest that this adaptive immune transformation method has the potential to
be widely used in multiple cancer types.

Jiang Wen, corresponding author of the paper, has shown great success in the treatment of blood tumors such as leukemia and lymphoma in recent years, but its effectiveness in solid tumors is poor
.
Therefore, scientists have been working to uncover the specific mechanisms
that lead to this treatment difference.
One explanation is that hematological and solid tumors express different immunomodulatory molecules, which affect how they interact
with immune cells.
Remarkably, a membrane-binding protein, signaling lymphocyte activation molecule family member 7 (SLAMF7), is crucial in activating human immune cells against cancer cells, acting as a "Eat Me" signal
.
However, SLAMF7 is found almost exclusively on the surface of blood cancer cells and is not expressed
in solid tumor cells.
To promote the expression of SLAMF7 in solid tumor cells, the research team developed a bispecific tumor-transforming nanoparticle (BiTN) platform
.
These nanoparticles contain two effector molecules, one that binds to the surface of the targeted tumor cells and the other responsible for activating the immune response
.
Bispecific tumor-transforming nanoparticles (BiTN) design schematic In this study, the research team used BiTN with SLAMF7 and Her2-recognizing antibodies to target Her2-positive breast cancer cells
.
This type of breast cancer is relatively more malignant than Her2-negative breast cancer and is more likely to develop drug
resistance.
The researchers found that these nanoparticles successfully attached SLAMF7 to the surface of Her2-positive breast cancer cells, guided immune cells to engulf it, and activated the cGAS-STING pathway of phagocytes, making tumors more sensitive
to immune checkpoint blocking therapy.
The Her2-SLAMF7 nanoparticles convert solid tumors into hematoid tumors, and the research team said that this method makes breast cancer cells more sensitive to immunotherapy with anti-CD47 antibodies, enhancing the killing effect
of immunotherapy on solid tumors.
In addition, in mouse experiments, this treatment method also significantly inhibited tumor growth without obvious toxic side effects
.
The combination of anti-CD47 and Her2-SLAMF7 nanoparticles induces targeted phagocytosis and macrophage activation in cancer cellsMore exciting, the BiTN platform has a wide range of potential applications in the treatment of solid tumors, an approach that does not specifically target one cancer type or one regulatory molecule, but has the potential to become a universal therapeutic strategy
for several different solid tumor types.
As a proof of concept, the research team also developed BiTN containing folic acid to target triple-negative breast cancer (the most difficult breast cancer) and obtained a good therapeutic effect
.
Dr.
Betty Kim, co-corresponding author of the study, said that because these nanoparticles are engineered structures, similar to plug-and-play "hot plugging", different tumor targeting agents or immune molecules can be combined onto the nanoparticle surface to target those tumor types that do not respond to immunotherapy, especially some refractory solid tumors
。 In mouse tumor models, the combination treatment of anti-CD47 and Her2-SLAMF7 nanoparticles induced a stronger anti-tumor immune responseAll in all, this study developed a treatment that transforms solid tumors into hematological tumors, bispecific tumor-transforming nanoparticles (BiTN), enabling immune transformation of solid tumors, making them more sensitive
to immunotherapy 。 At the same time, the study also highlights the potential of immune cells other than T cells, especially macrophages, as effectors of anti-tumor immunotherapy, and suggests that immune-activating molecules such as SLAMF7 may be powerful targets for the treatment of human cancer
.