Slingshot Biosciences’ Post

Identification of clinically relevant T cell receptors for personalized T cell therapy using combinatorial algorithms https://lnkd.in/g-_MGBEH

Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TILs) is a personalized immunotherapy approach with demonstrated superiority over second-line checkpoint blockade immunotherapy in patients most clearly demonstrated in melanomas. A central challenge in developing personalized cancer cell immunotherapy for other cancers is the identification of tumor-reactive T cell receptors (TCRs). By exploiting the distinct transcriptomic profile of various tumor-reactive T cells relative to bystander cells, as shown below, one can benchmark a “TRTpredictor”: an antigen-agnostic in silico predictor of the clonality and richness of tumor-reactive TCRs. The study cited integrates TRTpred with an avidity predictor to derive a combinatorial algorithm of clinically relevant TCRs for personalized T cell therapy applicable to a large variety of solid tumors. #adoptivecelltransfer #personalizedcancertreatment #tcrs #tumorreactivetcellreceptors #tumorinfiltratinglymphocytes #tils #cancerimmunotherapy #melanoma #solidtumors

The first cell therapy using DNA base editing without inducing double-strand breaks is entering clinical trials. If the method can indeed best CRISPR on safety and precision, it could be a game changer. The prospects of allogeneic cell therapy programs in particular would get a big boost. Folks across the C&GT space will be keeping a close eye on this one. Syntegon ISPE https://lnkd.in/e7sHqp-u

Identification of clinically relevant T cell receptors for personalized T cell therapy using combinatorial algorithms https://lnkd.in/g-_MGBEH

Discovery of tumor-reactive T cell receptors by massively parallel library synthesis and screening https://lnkd.in/eXaA3BKs

Tackling relapse after Cell therapy via enhanced CAR-T architecture with low affinity IL-2. 🔸 CAR T cell therapies show promise but often lack durable remissions. To improve efficacy, researchers developed a CAR enhancer (CAR-E), which fuses a CAR T cell antigen with an immunomodulatory molecule. 🔸 Using BCMA CAR T cells for #multiplemyeloma treatment, they created a CAR-E with BCMA fused to low-affinity IL-2. This enhances T cell activation and antitumor activity while reducing IL-2-related toxicities. 🔸 The BCMA CAR-E boosts CAR T cell #proliferation, #tumorclearance, and #memory cell development, which can re-expand upon restimulation to control tumor growth. This approach avoids specific engineering and allows for lower CAR T cell doses. #Celltherapy #CART #Relapse #IL-2 #Enhancer #BCMA #CAR-E #MultipleMyeloma

Byterna Therapeutics, in collaboration with Fudan University and University of Pennsylvania has published a research article entitled “Scarless circular mRNA-based CAR-T cell therapy elicits superior anti-tumor efficacy” on BioRxiv. We reported that cmRNA-based anti-CD19 CAR-T efficiently eliminated target cells in vivo and provided long-lasting antitumor efficacy. These results suggested that cmRNA could be a potent platform for unleashing full potential of mRNA technologies in cell therapies. Click https://lnkd.in/eR2Sqw7K for more information. #Byternatx #mRNA #CART

$TCBP Partners with CareDx, Inc. to Support #ACHIEVE Clinical Trial Using AlloCell for Pharmacokinetic Monitoring of Allogeneic Cell Therapy https://lnkd.in/eEXHzRfE Bryan Kobel Martin Thorp Toby Rintoul Callum Fiske

Excited to share this study, where we describe the ability to generate controlled ratios of CD4+ and CD8+ T cells from human pluripotent stem cells (PSCs) under fully defined conditions. Our findings reveal that precise control over Notch and T-cell receptor (TCR) signaling is essential to guide the differentiation of CD4+ T cells, which have proven challenging to produce. By fine-tuning the timing and intensity of these signals, we successfully promoted CD4+ lineage commitment, yielding T cells that could polarize into functional Th1, Th2, and Th17 subsets. Importantly, this approach generated mature, expandable T cells with diverse TCR repertoires, providing a great foundation for modeling human immune system development and for the development of cell therapies.

Programming B cells to treat Mucopolysaccharidosis Type I - Immusoft to Announce Positive Phase 1 Data for First Engineered B Cell Therapy in a Clinical Trial @immusoft #celltherapy #genetherapy