Internationella Barncancerdagen (2)

Man vill egentligen inte googla på barncancer,det då man får upp alldeles för mycket jobbigt att ta del av.
Men eftersom det snart är Barncancerdagen testade jag att googla med CAR T-Cell, om den metoden är möjlig för cancerdrabbade barn. Och jodå,forskare vid kända St. Jude Children Research Hospital är nånting på spåren. Igår 12/2 skickade de ut info att en forskargrupp via avancerad datateknologi + AI lyckats identifiera en beståndsdel av protein (peptid) som förstärker effekten av CAR T-Cell terapi till barn. Och förstår jag det rätt tror forskarna att upptäckten gör det möjligt att använda metoden på fler jobbiga barncancrar.

Novel bispecific design improves CAR T–cell immunotherapy for childhood leukemia

Scientists at St. Jude Children’s Research Hospital improved bispecific chimeric antigen receptor (CAR) T–cell immunotherapies for acute myeloid leukemia (AML), corroborated by computational analysis.

Memphis, Tennessee, February 12, 2024

St. Jude Children’s Research Hospital scientists improved chimeric antigen receptor (CAR) T–cell immunotherapy for acute myeloid leukemia (AML), demonstrating better efficacy in the lab. To overcome common problems with CAR T cells, the researchers created an additional means for the therapy to find and eliminate cancer cells, using a small peptide. The study also showed how a computational approach incorporating AlphaFold predicted protein models could help understand how structure impacts antigen recognition and therapy efficacy. The findings were published today in Cell Reports Medicine.

Immunotherapy that reprograms a patient’s own immune cells to target a cancer-specific protein, CAR T–cell therapy, has shown success in treating some relapsed leukemias. However, sometimes the treatment is unsuccessful because cancer cells that do not have the targeted protein can still grow, escaping the therapy and causing a relapse. The relapse rate for AML is high, leading to a poor prognosis for the disease overall. 

The St. Jude group thought it might be possible to overcome the problem of immune escape in AML models by targeting two different cancer-related proteins instead of just one. Others have attempted a similar approach but have encountered problems with the structure of the bispecific CAR. The scientists overcame these problems by adding a small peptide to the CAR to serve as the binder for the second targeted protein, then confirmed their results with computational structural analysis of their improved constructs. 

“One of the most exciting aspects of the study is that this approach can be widely extrapolated to other tumors,” said senior corresponding author Paulina Velasquez, MD, St. Jude Department of Bone Marrow Transplantation and Cellular Therapy. “We focused on leukemia, but combining bispecific CAR design with computational predictions can be widely extrapolated for other tumors such as solid and brain tumors.”

“We are one of few groups in the world to use AI-based structure prediction tools for CAR design,” said second author Kalyan Immadisetty, St. Jude Department of Bone Marrow Transplantation and Cellular Therapy. Immadisetty confirmed the association between short, flexible linkers and greater anti-cancer efficacy by comparing 3D-modeled structures. This information supported the performance of the CAR in real experimental outputs.

“Most importantly, others can now use our computational approach for designing their CARs,” Immadisetty said. “And hopefully, it will help them understand the efficacy of their CAR technology and lead to overall improvements for leukemia and other malignancies.”

På närmare håll har EU idag godkänt en stamcellsbehandling för barn från 12 års ålder och uppåt.

"The EU has just approved its first-ever CRISPR gene editing therapy."

European Commission Approves First CRISPR/Cas9 Gene-Edited Therapy, CASGEVY™ (exagamglogene autotemcel), for the Treatment of Sickle Cell Disease (SCD) and Transfusion-Dependent Beta Thalassemia (TDT)

ZUG, Switzerland and BOSTON, Feb. 13, 2024 (GLOBE NEWSWIRE) -- CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, announced today that the European Commission has granted conditional marketing authorization to CASGEVY™ (exagamglogene autotemcel [exa-cel]), a CRISPR/Cas9 gene edited therapy. CASGEVY is approved for the treatment of patients who are 12 years of age and older with severe sickle cell disease (SCD) characterized by recurrent vaso-occlusive crises (VOCs) or transfusion-dependent beta thalassemia (TDT), for whom hematopoietic stem cell (HSC) transplantation is appropriate and a human leukocyte antigen matched related HSC donor is not available.

“The approval by the European Commission is yet another important regulatory milestone underscoring the potentially transformative benefit of CASGEVY for patients with severe sickle cell disease and transfusion-dependent beta thalassemia,” said Samarth Kulkarni, Chairman and Chief Executive Officer of CRISPR Therapeutics. “There is a significant burden of these diseases across Europe, and we look forward to bringing this therapy to these patients in need.”

Några riktigt bra nyheter för cancerdrabbade barn om man försöker hitta nånting positivt mitt i eländet.

Vid googlingen dök flera CAR T-Cell nyheter upp.Jag väljer att nämna denna nyhet:

Using cancer's 'superpower' to boost T-cell therapies in mice

By Helen FloershFeb 12, 2024 3:30pm

When scientists inserted the CARD11-PIK3R3 mutation into healthy T cells and tested them against a line of leukemia cells, potency was dramatically increased. (Avesun/iStock/Getty Images Plus)

A naturally occurring mutation in T cells that leads to lymphoma can be weaponized to make engineered T-cell therapies more effective against cancer, including melanoma, findings from a new study in mice suggest.

In an article published Feb. 7 in Nature, scientists from Northwestern University and the University of San Francisco (UCSF) showed that a cancerous mutation that fuses a pair of genes, CARD11 and PIK3R3, has strong anti-cancer effects when added to T cells in chimeric antigen receptor T cell (CAR-T) and T cell receptor (TCR) therapies. The study’s co-leads, Northwestern dermatologist Jaehyuk Choi, M.D., Ph.D. and UCSF scientist Kole Roybal, Ph.D., have launched a new biotech company called Moonlight Bio to take their findings to the clinic.

“The superpower that makes cancer cells so strong can be transferred into T cell therapies to make them powerful enough to eliminate what were once incurable cancers,” Choi said in a press release from the university. 

Building on the basic principle that cancer cells contain gene mutations that make them more evolutionarily “fit”—that is, better at proliferating and resisting the immune system—the researchers systematically screened the impacts of 71 different mutations in cancerous T cells from patients with lymphoma. This led them to the CARD11-PIK3R3 mutation, which appeared to increase signaling by a group of proteins known as the CBM complex. CBM complex activity has been associated with malignant HER2-positive breast cancer, lymphoma and oral cancer (PDF). 

When the scientists inserted the CARD11-PIK3R3 mutation into healthy T cells and tested them against a line of leukemia cells, potency was dramatically increased. While 75% to 100% of the cancer cells remained after being cultured for two weeks with regular T cells, the ones that were cultured with T cells containing the CARD11-PIK3R3 mutation were almost completely eliminated. 

Fotnot! USCF är partners till PHI.

Min kommentar

Det tas stora kliv inom Reg Med området just nu. T-Cell/CAR T-Cell är dock mest omskrivet,och inte så konstigt kanske då forskarna nu fått bra insikter i hur kroppens eget immunförsvar fungerar och hur man kan omprogrammera dess celler till att bli supereffektiva cancerdödare.

Amerikanska Penn Medicine University var tidiga med att forska kring T-Celler och har bra kompetens inom området.

Såpass att de igår launchade en informationsvideo som berättar om CAR T-Cell och deras forskning.

#CARTcelltherapy has successfully cured blood cancers and has the potential to treat other diseases. Here, CAR T pioneer

@carlhjune

reflects on the early remarkable triumphs and shares the research being done now to expand this treatment within oncology and beyond.

Klicka på denna länk så ser ni videon. (twitter)

Forskaren Carl June berättar om cancersjuka 12-åriga Emily och hur hon botades (känslosamt att se).

Han fortsätter med att berätta : CAR T-Cell therapy to litterally every cancer you can think of. 

Jag rekommenderar starkt alla att titta på videon.

Ta er en funderare på hur stort T-Cell/CAR T-Cell kommer bli. Multiplicera det X gånger så är ni nära svaret.

                                              Mvh the99