Chimeric antigen receptor (CAR) T cell therapy shows promise against cancer. However, current methods activate T cells before engineering them, potentially limiting their effectiveness. This study explores blocking type I interferon, a natural immune response, during CAR T cell engineering of non-activated T cells. This approach aims to improve the efficiency of CAR integration and potentially lead to more potent CAR T cells for cancer treatment.

Here we show that Glut5-expressing CAR T cells have superior anti-tumor function to standard CAR Ts in a xenograft model of AML. Fructose supports maximal glycolytic capacity and ATP replenishment rates in GLUT5-expressing T cells cultured in glucose-free conditions. As fructose is abundant within the bone marrow of AML patients, our findings have immediate translational relevance, indicating that fructose can be repurposed as fuel for CAR T cells against AML.

• Considerations for TSCM-based CAR T products
• Autologous vs allogenic therapy
• Viral vs non-viral methodologies​

Current cancer immunotherapy struggles to harness the full potential of macrophages. This study explores innovative methods to engineer macrophages for tumor destruction. Investigating CAR M (Chimeric Antigen Receptor Macrophages) and in vivo reprogramming, the research proposes a revolutionary approach to rewire macrophages, leveraging their abilities to fight cancer.

This study proposes a precision medicine approach for B-cell malignancies using CAR T cells. It involves engineering T cells with a CAR that recognizes the IGHV4-34 B Cell Receptor (BCR). This targeted therapy aims to specifically eliminate malignant B-cells while sparing healthy B-cells, potentially leading to a more effective and safer treatment for B-cell malignancies.

Current CAR T cell therapy is constantly evolving. This study explores the use of messenger RNA (mRNA) technology for engineering next-generation CAR T cells. By harnessing mRNA's unique properties, researchers aim to create CAR T cells with improved functionality and efficacy, potentially leading to a new wave of more potent cancer treatments.

Current CAR T cell therapy often involves extracting and engineering T cells outside the body. This study explores in vivo generation of CAR T cells. This approach aims to create CAR T cells directly within a patient, potentially leading to improved therapeutic outcomes in immuno-oncology (IO) by overcoming limitations associated with ex vivo manipulation.

Insertion of an anti-CD34 antibody epitope into the hinge region of a CD33-directed CAR allowed purification of CAR-expressing cells using immunomagnetic separation by anti-CD34 microbeads. Microbead purification enabled >70% CAR+ cell recovery with a purity of >95%. In vitro killing assays of AML cell lines showed that untransduced cells contributed marginally to the potency of CAR-T cell drug product but may contribute to non-specific killing through indirect activation.

Current CAR T cell therapy for aggressive brain tumors shows limited success. This presentation explores next-generation CAR T cells, engineered with improved functionalities. These advancements aim to address challenges like immunosuppressive environments and antigen escape, potentially leading to more efficient targeting and destruction of gliomas.

Traditional T cell therapies for solid tumors face limitations. This study explores Integrated Circuit T Cells (ICTs), a novel engineered T cell design. ICTs incorporate multiple functionalities, overcoming challenges that use conventional methods. This research investigates ICTs as a promising approach for achieving more precise and effective targeting of solid tumors.

Inflammasomes are cytossolic multi-protein complexes associated with the innate immune system and activating the inflammatory response and cell death. Therefore, they are interesting for use in various therapies in medicine. In research literature, we can also see proposals for their possible use in the treatment of highly fatal glioblastoma. The presentation reviews the literature on the topic. One of the latest reports are the results of Park et al., who showed correlations between LLT-1 (ligand for the Natural Killer (NK) cell inhibitors NKRP1A receptor and NLRC4 inflammasome. High LLT-1 expression correlates with poor prognosis. This expression is associated with TNF and NOD-like receptor signaling pathway enrichment, indicating a potential role in tumor inflammation and progression. The NLRC4 and LLT-1 correlation may be used in the future for new therapies in glioblastoma using NK cells.

VIPER-101, a novel T cell therapy, targets T cell lymphoma. This approach engineers a patient's own immune cells (autologous) with a dual modification. First, it prevents self-targeting by the therapy. Second, it equips the cells to recognize and attack the cancer cells. This strategy, utilizing SENZA5 technology holds promise for a safer and more effective treatment of T cell lymphoma.

Stem cell memory T cells (TSCM) are optimal for CAR-T therapy due to their less differentiated state, which can result in better clinical responses and reduced toxicity. This presentation examines the development of TSCM -predominant allogeneic CAR-T using non-viral methods and discusses preclinical data supporting the improved efficacy and toxicity profiles of Poseida’s allogeneic CAR-T.