Cancer cell immune transformation nanotechnology platform

A team of researchers at the University of Texas MD Anderson Cancer Center has developed a nanotechnology platform that could change the way the immune system looks at solid tumor cells, making them more receptive to immunotherapy
.
The results of preclinical studies suggest that this adaptive immunotransformation method has the potential to
be widely used in multiple cancer types.

The study, published today in Nature Nanotechnology, details how the platform can be used to artificially attach activating molecules to the surface of tumor cells, triggering an immune response
in both cells.

.
 , M.
D.
, Ph.
D.
, assistant professor of Radiation Oncology, and Betty Kim, M.
D.
, Ph.
D.
, professor of Neurosurgery, co-led the study.

"With this new platform, we now have a strategy, at least immunologically, to transform solid tumors into tumors that resemble hematological tumors, which typically respond much more to immunotherapy," said
Assistant Professor Wen Jiang.
"If we can translate and validate this approach in the clinic, it may bring us closer to the maximum level
of activity of immunotherapy drugs for cancers that do not respond well to traditional ones.
"

Immunotherapy is highly effective for blood cancers such as leukemia and lymphoma, but has a different
success rate for solid tumors.
Scientists have been working to further understand the mechanisms
that prevent a better response.
One explanation is that different expressions of immunomodulatory molecules on blood cancer and solid tumor cells affect their interactions
with immune cells.

Signaling lymphocyte activation of molecular family members 7 (SLAMF7) receptors is essential in activating the body's immune cells against cancer cells, acting as a "eat me" signal
.
However, it is found almost exclusively on the surface of blood cancer cells, not in solid tumor cells, making it an attractive target
for researchers' immunotransformation approaches.

To facilitate the expression of SLAMF7 in solid tumor cells, the researchers developed a bispecific tumor-transforming nanoconjugate (BiTN) platform
.
These nanosystems are designed so that one molecule binds to the surface of the targeted tumor cell and another molecule activates the immune response
.

In this study, the researchers used BiTN with SLAMF7 and Her2-recognizing antibodies to target Her2-positive breast cancer cells
.
In laboratory models, nanoconjugates successfully attach SLAMF7 to breast cancer cells, leading to phagocytosis or uptake
by immune cells.
The approach also makes breast cancer cells more sensitive to treatment with anti-CD47 antibodies, which block the "don't eat me" signal sent by tumor cells, further increasing the response
of solid tumor cells.

According to the authors, one of the most exciting things about this platform is its wide range of potential applications
.
Rather than targeting one cancer type or one regulatory molecule, this approach has the potential to become a generic strategy
for several different solid tumor types.
As a proof of concept, the authors also developed BiTN containing folic acid, rather than anti-Her2 antibodies, to target triple-negative breast cancer and achieved similar results
.

"Because these are engineered structures, this can be used as a plug-and-play method to incorporate different tumor targeting agents or immune molecules onto the nanoparticle surface
," Kim said.
For patients with solid tumors that do not respond to immunotherapy, we see this as an additional advantage to target the part
of the tumor that does not respond.
”