Nature sub-journal paper details! CAR-T cells targeting CXCR5 are expected to treat feliestic lymphoma and chronic lymphocytic leukemia

January 17, 2021 // --- In a new study, researchers from Max Delbruck Molecular Medical Center in Germany developed a new CAR-T cell therapy.
found this approach to be very effective, especially in the fight against figular lymphoma and chronic lymphocytic leukemia (CLL).
results were published in the journal Nature Communications on 11 January 2021 under the title "CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin's mphlyoma and tumor-support follicular T helper cells".
from Nature Communications, 2021, doi:10.1038/s41467-020-20488-3.
's defenses don't usually recognize cancer cells as dangerous cells.
In order to correct this sometimes fatal error, the researchers are working on a clever new idea that involves extracting small amounts of immune cells from cancer patients and "reinventing" them in the lab so that they can identify certain surface proteins in malignant tumor cells.
then, they multiply these immune cells and inject them back into the blood of the same patient --- and let them begin to travel through the body, detecting and attacking all cancer cells in a targeted manner.
fact, the first treatments based on this concept have been approved.
so-called CAR-T cells have been used in Europe since 2018, especially in patients with B-cell lymphoma where traditional cancer treatments do not work.
T-cells are like the police force of the immune system.
CAR is an acronym for "embedded antigen --- which means that the cell police force is equipped with a new, lab-designed special antenna that can target a surface protein on cancer cells.
this antenna, a small number of T-cells can surround a large number of cancer cells and destroy them.
ideally, CAR-T cells can patrol the body for weeks, months or even years to prevent tumor recurrence.
a feature of B cells, antennas on CAR-T cells were primarily targeted at CD19 proteins carried on the surface of B cells.
this form of therapy is by no means effective for all patients.
In the new study, a team led by Dr. Uta Hoepken, head of the Autoimmune and Tumor Microenvironigning Laboratory at Max Delbrook Molecular Medical Center, developed a new form of therapy that allows T-cells in the lab to be sensitive to different identification characteristics--- the B-cell home protein CXCR5.
CXCR5 was first described more than 20 years ago at Max Delbrook Molecular Medical Center, and I've been working on this protein myself for almost a long time," Hoepken said.
In this, I am very pleased that we have now successfully used CXCR5 in the laboratory to effectively fight non-Hodgkin's lymphoma, such as fliatic lymphoma and sleeve lymphoma, as well as chronic lymphocytic leukemia.
" protein is a kind of digestion that helps mature B cells move from the bone marrow -- where they are produced -- to immune system organs such as lymph nodes and spleen.
, Hoepken explains, "Without this subject, B-cells would not be able to find their target location, the B-cell fleatic foam of the lymphatic organ."
all mature B cells, including malignant B cells, carry this subject on their surface," said Janina Pfeilschifter, ph.D. student with the Hoepken team and co-author of a suitable target paper.
so it seems to us that it is well suited to detect B-cell tumors, allowing CAR-T cells targeting CXCR5 to attack the cancer.
in our study, we have shown that this immunotherapy is likely to be safe and very effective in human cancer cells and in two mouse models.
" may be particularly suitable for patients with figular lymphoma or chronic lymphocytic leukemia.
, co-lead author of the paper, explained, "These two types of cancers involve not only B cells, but also auxiliary fage T cells that also carry CXCR5 on the surface.
" special antenna CXCR5-CAR, which targets this identifiable feature, was developed by Dr. Julia Bluhm as a Doctoral Student at the Translational Oncology Immunology Laboratory at Max Delbrook Molecular Medical Center, led by physician Dr. Armin Rehm.
Hoepken are both co-authors of the paper.
first successful Pfeilschifter and Bunse in a Petri dish first confirmed that various human cells, such as those from blood vessels, intestines, and the brain, do not carry CXCR5 subjects on their surfaces and therefore are not attacked by T cells equipped with CXCR5-CAR in petri dishes.
it's important to prevent accidental organ damage during treatment," explains Pfeilschifter, a researcher at Pfeilschifter.
, experiments with human tumor cell line showed that malignant B cells from different forms of B-non-Hodgkin's lymphoma showed this subject.
Joeg Westermann, of the Department of Hematology, Oncology and Oncology Immunology at the Schalette School of Medicine in Berlin, Germany, also provided the Hoepken team with tumor cells from patients with CLL or B-non-Hodgkin's lymphoma.
also be able to detect CXCR5 on the surface of all B lymphoma cells and auxiliary fister T cells," said Pfeilschifter, a member of the Pfeilschifter.
When she and Bunse put these tumor cells in a petri dish with CAR-T cells targeting CXCR5, 48 hours later, almost all of the malignant B cells and auxiliary filth T cells disappeared from tissue samples.
the researchers also tested the new treatment on two mouse models after finding that "leukemia mice were cured."
these CAR-T cells need to be injected into the blood of cancer patients," hoepken said.
, animal studies are needed to confirm that they return to the microenn environment where the cancer is located and multiply there, and then do their work effectively.
" A mouse model has a severely suppressed immune system and can therefore be treated with human CAR-T cells without causing rejection.
also developed a CLL mouse model specifically for this study," Bunse reported.
We injected these mice with CAR-T cells that targeted CXCR5 by infusion, eliminating mature B-cells and auxiliary T-cells, including malignant B-cells, from the B-cell flease of the lymphatic organ.
" the researchers found no serious side effects in mice.
, "We know from the experience of cancer patients that CAR-T cell therapy increases the risk of infection within a few months.
" but in clinical practice, this side effect is almost always easy to control.
a clinical trial in progress, Hoepken stressed, "No laboratory can do such research alone."
thanks to the successful collaboration of many colleagues at max-delbruck Molecular Medical Center and Berlin's Schalette School of Medicine.
for her, the study is the first step toward building a "living drug--- similar to other cellular immunotherapy being developed at Max Delbrook Molecular Medical Center.
Rehm added, "We have worked with two cancer specialists at the Schalette School of Medicine in Berlin and are currently working with them to prepare phase 1/2 clinical trials."
both hope that the first patients will begin to benefit from their new CAR-T cell therapy in the near future.
: 1. Mario Bunse et al. CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin’s lymphoma and tumor-supportive follicular T helper cells. Nature Communications, 2021, doi:10.1038/s41467-020-20488-3.2.A potent weapon against lymphomas